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Basic-Jukic N, Pavlisa G, Sremec NT, Juric I, Ledenko R, Rogic D, Jelakovic B. Autoantibodies in COVID-19, a possible role in the pathogenesis of the disease. Ther Apher Dial 2023; 27:882-889. [PMID: 37217275 DOI: 10.1111/1744-9987.14004] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 04/25/2023] [Accepted: 05/07/2023] [Indexed: 05/24/2023]
Abstract
OBJECTIVES In this study, we investigated whether SARS-CoV-2 stimulates autoantibody production. METHODS The study included 91 patients hospitalized due to COVID 19, with no previous history of immunological diseases. Immunofluorescence assays were performed to detect antinuclear antibodies (ANAs) and antineutrophil cytoplasmic antibodies (ANCAs), along with tests for specific autoantibodies. RESULTS The median age (57% male) was 74 years (range 38-95 years). Autoantibodies were positive in 67 (74%), ANA in 65 (71%), and ANCA in 11 (12%) patients. Female gender (p = 0.01), age (p = 0.005), and Charlson comorbidity index (p = 0.004) were significant predictors for the development of ANA/ANCA antibodies (p = 0.004). Nuclear mitotic apparatus (NuMA)-like, positivity was the strongest predictor of acute kidney injury (AKI), together with noninvasive ventilation and eGFR (χ2 = 49.01, P < 0.001). CONCLUSION Positive autoantibodies in a large proportion of patients suggest a role of autoimmunity in the pathophysiology of acute COVID-19 disease. NuMA was the strongest predictor of AKI.
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Affiliation(s)
- Nikolina Basic-Jukic
- Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, Zagreb, Croatia
- School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Gordana Pavlisa
- School of Medicine, University of Zagreb, Zagreb, Croatia
- Department for Respiratory Diseases Jordanovac, University Hospital Center Zagreb, Zagreb, Croatia
| | - Nada Tomic Sremec
- Department for Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia
| | - Ivana Juric
- Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, Zagreb, Croatia
| | - Robert Ledenko
- School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Dunja Rogic
- Department for Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia
| | - Bojan Jelakovic
- Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, Zagreb, Croatia
- School of Medicine, University of Zagreb, Zagreb, Croatia
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Chauhan R, Jain D, Tiwari AK, Dorwal P, Raina V, Nandi SP. Laboratory Diagnosis of ANCA-Associated Vasculitis (AAV) Using a Combination of Immunofluorescence Test (IIFT) and Line Immunoassay (LIA): Single-Centre Report From India. REUMATOLOGIA CLINICA 2022; 18:15-19. [PMID: 35090607 DOI: 10.1016/j.reumae.2020.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 08/06/2020] [Indexed: 06/14/2023]
Abstract
INTRODUCTION Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a small vessel vasculitis with insufficient epidemiological estimates in India. We aimed to determine demographic, clinical features, and laboratory diagnosis of AAV patients presenting to a large tertiary care centre in India. MATERIAL AND METHODS 1289 patient samples were screened for ANCA by indirect immunofluorescence test (IIFT) and confirmation of ANCA target antigens was done by line immunoassay. Association between IIFT and LIA was determined in AAV. RESULTS By IIFT, ANCA was detected in 13.0% (168 out of 1289), of which 23.8% (40/168) were positive with P-ANCA pattern, 25.0% (42/168) were positive with C-ANCA and 47.6% (80/168) showed an atypical pattern. On evaluation with a line immunoassay, 6.7% (86/1289) were positive out of which 52.3% (45/86), 41.9% (36/86), 8.8% (6/86) were positive for anti-MPO, anti-PR3, and anti-GBM respectively. In eosinophilic granulomatosis with polyangiitis (EGPA) 87.5% (7/8), and microscopic polyangiitis (MPA/RLV) 91.3% (21/23), anti-MPO was the predominantly observed antibody. In granulomatosis with polyangiitis (GPA) anti-PR3 antibody was predominant in 87.5% (28/32) cases. Out of 168 IIF positive samples 8, 32, and 23 cases of EGPA, GPA, and MPA/RLV were observed respectively. CONCLUSIONS The primary aim of the study was to provide single-centre data to determine the laboratory diagnosis of AAV. A combination of IIFT and LIA was found to be an optimum testing strategy for the laboratory diagnosis of AAV.
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Affiliation(s)
- Rajni Chauhan
- Molecular and Transplant Immunology Laboratory, Department of Transfusion Medicine, Medanta-The Medicity, Gurgaon, India; Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India
| | - Dharmendra Jain
- Molecular and Transplant Immunology Laboratory, Department of Transfusion Medicine, Medanta-The Medicity, Gurgaon, India
| | - Aseem Kumar Tiwari
- Molecular and Transplant Immunology Laboratory, Department of Transfusion Medicine, Medanta-The Medicity, Gurgaon, India
| | - Pranav Dorwal
- Molecular and Transplant Immunology Laboratory, Department of Transfusion Medicine, Medanta-The Medicity, Gurgaon, India
| | - Vimarsh Raina
- Chimera Transplant Research Foundation, New Delhi, India
| | - Shoma Paul Nandi
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India.
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Yang W, Zhou Z, Wu H, Liu C, Shen B, Ding S, Zhou Y. Multi-function PtCo nanozymes/CdS nanocrystals@graphene oxide luminophores and K 2S 2O 8/H 2O 2 coreactants-based dual amplified electrochemiluminescence immunosensor for ultrasensitive detection of anti-myeloperoxidase antibody. J Nanobiotechnology 2021; 19:225. [PMID: 34325706 PMCID: PMC8323290 DOI: 10.1186/s12951-021-00968-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Accepted: 07/22/2021] [Indexed: 11/10/2022] Open
Abstract
Background Anti-myeloperoxidase antibody (anti-MPO) is an important biomarker for anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAVs). However, the complicated operation procedures and insufficient sensitivity of conventional anti-MPO detection methods limit their application in monitoring efficacy of AAVs in clinical diagnosis. Herein, a dual amplified electrochemiluminescence (ECL) immunosensor based on multi-function PtCo nanozymes/CdS nanocrystals@graphene oxide (PtCo/CdS@GO) luminophores and K2S2O8/H2O2 coreactants has been fabricated for ultrasensitive detection of anti-MPO. Results PtCo/CdS@GO luminophores as novel signal amplification labels and nanocarriers to load rabbit anti-mouse IgG were synthesized by co-doping with Pt and Co nanozymes simultaneously with several considerable advantages, including astonishing peroxidase-like catalytic activity, high-efficiency luminescence performance and superior stability in aqueous solutions. Meanwhile, upon the K2S2O8/H2O2 coreactants system, benefiting from the efficient peroxidase-like activity of the PtCo/CdS@GO toward H2O2, massive of transient reactive intermediates could react with K2S2O8, thus obtaining higher ECL emission. Therefore, the developed ECL immunosensor for anti-MPO detection displayed good analytical performance with good concentration linearity in the range of 0.02 to 1000 pg/mL and low detection limit down to 7.39 fg/mL. Conclusions The introduction of multi-function PtCo/CdS@GO luminophores into the established ECL immunoassay not only was successfully applied for specific detection of anti-MPO in clinical serum samples, but also provided a completely new concept to design other high-performance luminophores. Meaningfully, the ECL immunoassay strategy held wide potential for biomarkers detection in clinical diagnosis. Graphic abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s12951-021-00968-4.
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Affiliation(s)
- Wei Yang
- Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China.,Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Zheng Zhou
- Department of Clinical Laboratory, Chongqing University Three Gorges Hospital, Chongqing, 404000, China.,Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Haiping Wu
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Changjin Liu
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Bo Shen
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Shijia Ding
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
| | - Yonglie Zhou
- Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China.
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Said D, Rashad NM, Abdelrahmanc NS, Dawaa GA. Antineutrophil Cytoplasmic Antibody in Lupus Nephritis: Correlation with Clinicopathological Characteristics and Disease Activity. Curr Rheumatol Rev 2021; 17:213-221. [PMID: 33292154 DOI: 10.2174/1573397116999201208213422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 10/09/2020] [Accepted: 10/27/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Lupus nephritis (LN) represents 40%-50% of all systemic lupus erythematosus (SLE) patients, and rapidly progressive glomerulonephritis is associated with significant morbidity and mortality. Antineutrophil cytoplasmic antibody (ANCA) might be involved in the pathogenesis of LN. OBJECTIVE We evaluated the role of myeloperoxidase (MPO)-ANCA, proteinase 3 (PR3)-ANCA, and anti-glomerular basement membrane autoantibodies (anti-GBM autoAb) for the diagnosis of LN. METHODS In this cross-sectional study, 95 SLE patients were divided into 2 subgroups: LN group (n = 60) and non-LN group (n = 35). For further analysis, we subclassified the LN group into ANCA- positive (n = 16) and ANCA-negative (n = 44) LN patients. The entire Non-LN group was ANCA- negative. The SLE disease activity index (SLEDAI) was reported for each patient. Determination of MPO-ANCA, PR3-ANCA, and anti-GBM autoAb was performed using a novel multiplex bead-based technology in all patients. Data analyses were done using SPSS, version 20. Approval was obtained from the institutional review board of Zagazig University (ZU-IRB#6000). RESULTS Of 95 patients with SLE, 16 patients (16.84%) had ANCA-positive LN, all of which were MPO-ANCA. There was a positive correlation between MPO-ANCA and SLEDAI, as well as with class IV LN. Receiver operating characteristic analyses revealed that the sensitivity and specificity of MPO-ANCA were 81.3% and 99.8%, respectively, in discriminating LN from systemic lupus without nephritis. CONCLUSION MPO-ANCA level was significantly correlated with SLEDAI, inflammatory markers, kidney function tests, and LN class IV.
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Affiliation(s)
- Dina Said
- Rheumatology and Rehabilitation Department, Faculty of Medicine, Zagazig University, Egypt
| | | | | | - Ghada Aboelsaud Dawaa
- Clinical Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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Rodríguez E, Latzke B, Sierra M, Romera AM, Siedel D, Agraz I, Soler MJ, García-Carro C, Draibe J, de la Prada FJ, Villacorta J, Buxeda A, Sierra-Ochoa A, Lozano I, Durán X, Barrios C, Pascual J. Antimyeloperoxidase and proteinase 3 antibodies for nephritis flare prediction in ANCA-associated-vasculitis. Nephrol Dial Transplant 2021; 37:697-704. [PMID: 33533909 DOI: 10.1093/ndt/gfab020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND The value of myeloperoxidase and proteinase 3 antibodies titers in the assessment of renal disease activity and flare prediction in patients with ANCA-associated-vasculitis (AAV) is not well-known. METHODS Retrospective study including 113 AVV patients with a renal biopsy-proven pauci-immune necrotizing glomerulonephritis from seven Spanish hospitals. The main inclusion criteria were assessment of MPO antibodies (MPOab) using multiplex flow immunoassay and PR3 antibodies (PR3ab) measurements using immunoassay chemiluminescence with an identical range of values for all participating centers. RESULTS Serum MPOab, 3 ± 1.2 months before relapse, was higher in patients who relapsed (19.2 ± 12.2 vs 3.2 ± 5.1 AI, p < 0.001). The discrimination value of MPOab 3 months before renal relapse had an AUC of 0.82 (95%CI 0.73-0.92; p < 0.001). ΔMPOab (change in antibodies titration 6 months before relapse) was higher in patients who relapsed [8.3 ± 12 vs 0.9 ± 3.1 AI, p = 0.001) (AI; antibody index unit). The discrimination value of ΔMPO had an AUC of 0.76 (95%CI 0.63-0.88; p < 0.001). The positive predictive value of renal relapse in PR3 patients is 100% and the negative predictive value of renal relapse in patients with PR3 positive titers is 57.1%. Serum PR3ab was higher in patients who relapsed 2.8 ± 1.4 months before relapse (58.6 ± 24.6 vs 2.0 ± 0.6 AI, p < 0.001). CONCLUSIONS MPO antibody level monitorization using multiplex flow immunoassay and PR3 measurements using immunoassay chemiluminescence are useful and sensitive tools for the prediction of renal relapse in the follow-up of AAV patients with renal disease, and relevant surrogate markers of renal disease activity.
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Affiliation(s)
- Eva Rodríguez
- Servicio de Nefrología. Hospital del Mar, Barcelona, Spain
| | - Belén Latzke
- Servicio de Nefrología. Hospital del Mar, Barcelona, Spain
| | - Milagros Sierra
- Servicio de Nefrología. Hospital San Pedro de Logroño, La Rioja, Spain
| | - Ana María Romera
- Servicio de Nefrología. Hospital General Universitario de Ciudad Real, Spain
| | - Diego Siedel
- Servicio de Nefrología. Hospital General Universitario de Ciudad Real, Spain
| | - Irene Agraz
- Servicio de Nefrologia, Hospital Universitario Valle Hebrón, Barcelona, Spain
| | - María José Soler
- Servicio de Nefrologia, Hospital Universitario Valle Hebrón, Barcelona, Spain
| | - Clara García-Carro
- Servicio de Nefrologia, Hospital Universitario Valle Hebrón, Barcelona, Spain
| | | | | | - Javier Villacorta
- Servicio Nefrologia. Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Anna Buxeda
- Servicio de Nefrología. Hospital del Mar, Barcelona, Spain
| | | | - Inés Lozano
- Laboratori de Referència de Catalunya, Spain
| | - Xavier Durán
- AMIB. Institut Hospital del Mar Investigación Médica, Barcelona, Spain
| | - Clara Barrios
- Servicio de Nefrología. Hospital del Mar, Barcelona, Spain
| | - Julio Pascual
- Servicio de Nefrología. Hospital del Mar, Barcelona, Spain
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Won DI, Park J, Kim BS, Kim CE, Yoon HS, Jung JS. Stratification of Nuclear Homogeneous Patterns on HEp-2 Cells Based on Neutrophil Nuclear Staining. Chonnam Med J 2021; 57:51-57. [PMID: 33537219 PMCID: PMC7840351 DOI: 10.4068/cmj.2021.57.1.51] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 12/21/2020] [Accepted: 12/22/2020] [Indexed: 11/06/2022] Open
Abstract
Antinuclear antibody (ANA) testing is used to diagnose systemic autoimmune rheumatic disease (SARD). Nuclear homogeneous patterns on ANA-HEp-2 cells can result from anti-double-stranded DNA (dsDNA), anti-nucleosome, anti-histone, anti-Scl-70, or anti-dense fine speckles 70 (DFS70) antibodies (Abs). This study aimed to find a way to discriminate DFS70 Abs from others by way of assessing neutrophil nuclear staining on anti-neutrophil cytoplasmic antibody (ANCA) testing. Nuclear staining on ANCA-neutrophils was assessed to stratify nuclear homogeneous patterns on ANA-HEp-2 cells. Enrolled subjects included (1) young individuals with a dense fine speckled pattern on ANA testing (young non-SARD group, n=71) and patients with (2) systemic lupus erythematosus (SLE group, n=35); (3) rheumatoid arthritis possibly with histone, nucleosome Abs, and others (RA group, n=51); and (4) diffuse systemic sclerosis with Scl-70 Abs (diffuse SSc group, n=19). Negative rates (95% confidence interval) of neutrophil nuclear staining were 97.2% (90.2%-99.7%) in the young non-SARD group, 2.9% (0.1%-14.9%) in the SLE group, 3.9% (0.5%-13.5%) in the RA group, and 47.4% (24.5%-71.1%) in the diffuse SSc group. The negative rate of the young non-SARD group was significantly higher than those of the other groups (all p<0.05). In conclusion, this study suggests that the assessment of nuclear staining on ANCA-neutrophils can help to stratify nuclear homogeneous patterns on ANA-HEp-2 cells and thus to determine whether the ANA pattern is attributed to DFS70 Abs, which can be found in healthy individuals, especially in young individuals.
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Affiliation(s)
- Dong Il Won
- Department of Clinical Pathology, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jihea Park
- Department of Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Beom Soo Kim
- Department of Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Chae Eun Kim
- Department of Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Heon Sik Yoon
- Department of Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Ji Soo Jung
- Department of Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
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Crescente JG, Dellavance A, Diniz MA, Carrilho FJ, de Andrade LEC, Cançado ELR. Antineutrophil cytoplasmic antibody profiles differ according to type of primary sclerosing cholangitis and autoimmune hepatitis. Clinics (Sao Paulo) 2021; 76:e2228. [PMID: 33567045 PMCID: PMC7847259 DOI: 10.6061/clinics/2021/e2228] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 12/09/2020] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES To determine the frequency of the antineutrophil cytoplasmic antibodies (ANCA), antiproteinase-3 and antimyeloperoxidase, in primary sclerosing cholangitis (PSC) with or without inflammatory bowel disease (IBD+ or IBD-) and in different types of autoimmune hepatitis (AIH). Additionally, to verify the agreement between ANCA patterns by indirect immunofluorescence and their antigenic specificities by ELISA. METHODS For this study, 249 patients were enrolled (42 PSC/IBD+; 33 PSC/IBD-; 31 AIH type-1; 30 AIH type-2; 31 AIH type-3; 52 primary biliary cirrhosis; 30 healthy controls) whose serum samples were tested for ANCA autoantibodies. RESULTS There were fewer female subjects in the PSC/IBD- group (p=0.034). Atypical perinuclear-ANCA was detected more frequently in PSC/IBD+ patients than in PSC/IBD- patients (p=0.005), and was significantly more frequent in type-1 (p<0.001) and type-3 AIH (p=0.012) than in type-2 AIH. Proteinase-3-ANCA was detected in 25 samples (only one with cytoplasmic-ANCA pattern), and more frequently in PSC/IBD+ than in PSC/IBD- patients (p=0.025). Myeloperoxidase-ANCA was identified in eight samples (none with the perinuclear-ANCA pattern). Among the 62 reactive samples for atypical perinuclear-ANCA, 13 had antigenic specific reactions for proteinase-3 and myeloperoxidase. CONCLUSIONS PSC/IBD+ differed from PSC/IBD- in terms of sex and proteinase 3-ANCA and atypical perinuclear-ANCA reactivity, the latter of which was more frequently detected in type-1 and type-3 AIH than in type-2 AIH. There was no agreement between ANCA patterns and antigenic specificities in IBD and autoimmune liver diseases, which reinforces the need for proteinase-3 and myeloperoxidase antibody testing.
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Affiliation(s)
- Juliana Goldbaum Crescente
- Departamento de Gastroenterologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, BR
- Laboratorio de Investigacao Medica (LIM 06), Instituto de Medicina Tropical, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Alessandra Dellavance
- Disciplina de Reumatologia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, SP, BR
- Divisao de Pesquisa e Desenvolvimento, Laboratorios Fleury Medicina e Saude, Sao Paulo, SP, BR
| | - Marcio Augusto Diniz
- Biostatistics and Bioinformatics Research Center, Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Flair Jose Carrilho
- Departamento de Gastroenterologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Luis Eduardo Coelho de Andrade
- Disciplina de Reumatologia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, SP, BR
- Divisao de Pesquisa e Desenvolvimento, Laboratorios Fleury Medicina e Saude, Sao Paulo, SP, BR
| | - Eduardo Luiz Rachid Cançado
- Departamento de Gastroenterologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, BR
- Laboratorio de Investigacao Medica (LIM 06), Instituto de Medicina Tropical, Universidade de Sao Paulo, Sao Paulo, SP, BR
- *Corresponding author. E-mail:
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Chauhan R, Jain D, Tiwari AK, Dorwal P, Raina V, Nandi SP. Laboratory Diagnosis of ANCA-Associated Vasculitis (AAV) Using a Combination of Immunofluorescence Test (IIFT) and Line Immunoassay (LIA): Single-Centre Report From India. REUMATOLOGIA CLINICA 2020; 18:S1699-258X(20)30202-3. [PMID: 33060031 DOI: 10.1016/j.reuma.2020.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 08/06/2020] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a small vessel vasculitis with insufficient epidemiological estimates in India. We aimed to determine demographic, clinical features, and laboratory diagnosis of AAV patients presenting to a large tertiary care centre in India. MATERIAL AND METHODS 1289 patient samples were screened for ANCA by indirect immunofluorescence test (IIFT) and confirmation of ANCA target antigens was done by line immunoassay. Association between IIFT and LIA was determined in AAV. RESULTS By IIFT, ANCA was detected in 13.0% (168 out of 1289), of which 23.8% (40/168) were positive with P-ANCA pattern, 25.0% (42/168) were positive with C-ANCA and 47.6% (80/168) showed an atypical pattern. On evaluation with a line immunoassay, 6.7% (86/1289) were positive out of which 52.3% (45/86), 41.9% (36/86), 8.8% (6/86) were positive for anti-MPO, anti-PR3, and anti-GBM respectively. In eosinophilic granulomatosis with polyangiitis (EGPA) 87.5% (7/8), and microscopic polyangiitis (MPA/RLV) 91.3% (21/23), anti-MPO was the predominantly observed antibody. In granulomatosis with polyangiitis (GPA) anti-PR3 antibody was predominant in 87.5% (28/32) cases. Out of 168 IIF positive samples 8, 32, and 23 cases of EGPA, GPA, and MPA/RLV were observed respectively. CONCLUSIONS The primary aim of the study was to provide single-centre data to determine the laboratory diagnosis of AAV. A combination of IIFT and LIA was found to be an optimum testing strategy for the laboratory diagnosis of AAV.
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Affiliation(s)
- Rajni Chauhan
- Molecular and Transplant Immunology Laboratory, Department of Transfusion Medicine, Medanta-The Medicity, Gurgaon, India; Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India
| | - Dharmendra Jain
- Molecular and Transplant Immunology Laboratory, Department of Transfusion Medicine, Medanta-The Medicity, Gurgaon, India
| | - Aseem Kumar Tiwari
- Molecular and Transplant Immunology Laboratory, Department of Transfusion Medicine, Medanta-The Medicity, Gurgaon, India
| | - Pranav Dorwal
- Molecular and Transplant Immunology Laboratory, Department of Transfusion Medicine, Medanta-The Medicity, Gurgaon, India
| | - Vimarsh Raina
- Chimera Transplant Research Foundation, New Delhi, India
| | - Shoma Paul Nandi
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India.
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Nagy G, Csípő I, Tarr T, Szűcs G, Szántó A, Bubán T, Sipeki N, Szekanecz Z, Papp M, Kappelmayer J, Antal-Szalmás P. Anti-neutrophil cytoplasmic antibody testing by indirect immunofluorescence: Computer-aided versus conventional microscopic evaluation of routine diagnostic samples from patients with vasculitis or other inflammatory diseases. Clin Chim Acta 2020; 511:117-124. [PMID: 33002474 DOI: 10.1016/j.cca.2020.09.031] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 08/29/2020] [Accepted: 09/21/2020] [Indexed: 12/30/2022]
Abstract
BACKGROUND Detection of anti-neutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence assays (IFA) is of diagnostic importance in vasculitides and some other inflammatory diseases. Automation of IFA may be beneficial in high-throughput clinical laboratories. An analytical appraisal of the EUROPattern (EPa) automated microscope and image analysis system has not been reported in a routine clinical laboratory setting testing samples from both vasculitis and non-vasculitis patients. METHODS Results of EPa and on-screen ANCA pattern recognition of 568 consecutive routine serum samples were compared to those of conventional visual evaluation. RESULTS Agreement of discrimination between negative and non-negative samples was 86.1% comparing EPa and conventional reading, and it increased to 96.7% after on-screen user validation. Importantly, from the 334 samples classified as negative by EPa 328 (98.2%) were also negative by conventional evaluation. Pattern recognition showed 'moderate' agreement between classical microscopic and EPa analysis (κ = 0.446) and 'very good' agreement after user validation (κ = 0.900). Misclassification by EPa was dominantly due to the presence of anti-nuclear/cytoplasmic antibodies (incorrect pattern, 80/568) and the lower fluorescence cut-off of the automated microscope (false positives, 73/568). CONCLUSIONS Automated ANCA testing by EPa is a reliable alternative of classical microscopic evaluation, though classification of sera needs correction by trained personnel during on-screen validation.
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Affiliation(s)
- Gábor Nagy
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - István Csípő
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Tünde Tarr
- Institute of Internal Medicine, Department of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Gabriella Szűcs
- Institute of Internal Medicine, Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Antónia Szántó
- Institute of Internal Medicine, Department of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Tamás Bubán
- Institute of Internal Medicine, Department of Gastroenterology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Nóra Sipeki
- Institute of Internal Medicine, Department of Gastroenterology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Zoltán Szekanecz
- Institute of Internal Medicine, Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Mária Papp
- Institute of Internal Medicine, Department of Gastroenterology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - János Kappelmayer
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Péter Antal-Szalmás
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
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10
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Moiseev S, Cohen Tervaert JW, Arimura Y, Bogdanos DP, Csernok E, Damoiseaux J, Ferrante M, Flores-Suárez LF, Fritzler MJ, Invernizzi P, Jayne D, Jennette JC, Little MA, McAdoo SP, Novikov P, Pusey CD, Radice A, Salama AD, Savige JA, Segelmark M, Shoenfeld Y, Sinico RA, Sousa MJ, Specks U, Terrier B, Tzioufas AG, Vermeire S, Zhao MH, Bossuyt X. 2020 international consensus on ANCA testing beyond systemic vasculitis. Autoimmun Rev 2020; 19:102618. [PMID: 32663621 DOI: 10.1016/j.autrev.2020.102618] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 03/08/2020] [Indexed: 02/07/2023]
Abstract
This document follows up on a 2017 revised international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in granulomatosis with polyangiitis and microscopic polyangiitis and focuses on the clinical and diagnostic value of ANCA detection in patients with connective tissue diseases, idiopathic interstitial pneumonia, autoimmune liver diseases, inflammatory bowel diseases, anti-glomerular basement membrane (GBM) disease, infections, malignancy, and during drug treatment. Current evidence suggests that in certain settings beyond systemic vasculitis, ANCA may have clinical, pathogenic and/or diagnostic relevance. Antigen-specific ANCA targeting proteinase-3 and myeloperoxidase should be tested by solid phase immunoassays in any patient with clinical features suggesting ANCA-associated vasculitis and in all patients with anti-GBM disease, idiopathic interstitial pneumonia, and infective endocarditis associated with nephritis, whereas in patients with other aforementioned disorders routine ANCA testing is not recommended. Among patients with autoimmune liver diseases or inflammatory bowel diseases, ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1 who do not have conventional autoantibodies or in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn's disease. In these cases, ANCA should be tested by indirect immunofluorescence as the target antigens are not yet well characterized. Many questions concerning the optimal use of ANCA testing in patients without ANCA-associated vasculitis remain to be answered.
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Affiliation(s)
- Sergey Moiseev
- Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia.
| | - Jan Willem Cohen Tervaert
- Department of Medicine, Division of Rheumatology, University of Alberta, Edmonton, Canada and Maastricht University, Maastricht, The Netherlands
| | - Yoshihiro Arimura
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Dimitrios P Bogdanos
- Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece
| | - Elena Csernok
- Department of Internal Medicine, Rheumatology and Immunology, Vasculitis-Center Tübingen-Kirchheim, Medius Klinik Kirchheim, University of Tübingen, Kirchheim-Teck, Germany
| | - Jan Damoiseaux
- Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Marc Ferrante
- University Hospitals Leuven, Department of Gastroenterology and Hepatology, KU Leuven, Leuven, Belgium
| | - Luis Felipe Flores-Suárez
- Primary Systemic Vasculitides Clinic, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
| | - Marvin J Fritzler
- Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Pietro Invernizzi
- Division Gastroenterology and Center for Autoimmune Liver Diseases, University of Milano-Bicocca School of Medicine, Monza, Italy
| | - David Jayne
- Department of Medicine, University of Cambridge, Cambridge, UK
| | - J Charles Jennette
- Division of Nephropathology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA
| | - Mark A Little
- Trinity Health Kidney Centre, Trinity Translational Medicine Institute, Dublin, Ireland
| | - Stephen P McAdoo
- Centre for Inflammatory Disease, Department of Medicine, Imperial College London, London, UK
| | - Pavel Novikov
- Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Charles D Pusey
- Centre for Inflammatory Disease, Department of Medicine, Imperial College London, London, UK
| | - Antonella Radice
- Microbiology and Virology Institute, ASST Santi Paolo e Carlo, San Carlo Borromeo Hospital, Milan, Italy
| | - Alan D Salama
- UCL Department of Renal Medicine, Royal Free Hospital, London, UK
| | - Judith A Savige
- Department of Medicine, Melbourne Health, University of Melbourne, Melbourne, Australia
| | - Mårten Segelmark
- Department of Clinical Sciences, Lund University, Department of Nephrology and Rheumatology, Skane University Hospital, Lund, Sweden
| | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Renato A Sinico
- Department of Medicine and Surgery, Università degli Studi di Milano-Bicocca, Monza, Italy
| | - Maria-José Sousa
- Immunopathology and Autoimmunity Department, Centro de Medicina Laboratorial Germano de Sousa, Lisbon, Portugal
| | - Ulrich Specks
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| | - Benjamin Terrier
- Department of Internal Medicine, National Referral Center for Rare Systemic and Autoimmune Diseases, Hôpital Cochin, Paris, France
| | - Athanasios G Tzioufas
- Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Severine Vermeire
- University Hospitals Leuven, Department of Gastroenterology and Hepatology, KU Leuven, Leuven, Belgium
| | - Ming-Hui Zhao
- Renal Division, Peking University First Hospital, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Peking-Tsinghua Centre for Life Sciences, Beijing, China
| | - Xavier Bossuyt
- Laboratory Medicine, University Hospitals Leuven, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
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11
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de Graeff N, Groot N, Brogan P, Ozen S, Avcin T, Bader-Meunier B, Dolezalova P, Feldman BM, Kone-Paut I, Lahdenne P, Marks SD, McCann L, Pilkington C, Ravelli A, van Royen A, Uziel Y, Vastert B, Wulffraat N, Kamphuis S, Beresford MW. European consensus-based recommendations for the diagnosis and treatment of rare paediatric vasculitides - the SHARE initiative. Rheumatology (Oxford) 2020; 58:656-671. [PMID: 30535249 DOI: 10.1093/rheumatology/key322] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Accepted: 09/04/2018] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES The European initiative Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) aimed to optimize care for children with rheumatic diseases. Systemic vasculitides are very rare in children. Consequently, despite recent advances, paediatric-specific information is sparse. The lack of evidence-based recommendations is an important, unmet need. This study aimed to provide recommendations for diagnosing and treating children with rare forms of childhood systemic vasculitis. METHODS Recommendations were developed by a consensus process in accordance with the European League Against Rheumatism standard operating procedures. A systematic literature review informed the recommendations, which were devised and evaluated by a panel of experts via an online survey, and two consensus meetings using nominal group technique. Recommendations were accepted when ⩾ 80% of experts agreed. RESULTS Ninety-three relevant articles were found, and 78 recommendations were accepted in the two consensus meetings. General, cross-cutting recommendations and disease-specific statements regarding the diagnosis and treatment of childhood-onset PAN, granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and Takayasu arteritis are provided. CONCLUSION These Single Hub and Access point for paediatric Rheumatology in Europe recommendations were formulated through an evidence-based consensus process to support uniform, high-quality standard of care for children with rare forms of paediatric systemic vasculitis.
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Affiliation(s)
- Nienke de Graeff
- Department of Paediatric Rheumatology, Wilhelmina Children's Hospital, Utrecht
| | - Noortje Groot
- Department of Paediatric Rheumatology, Wilhelmina Children's Hospital, Utrecht.,Department of Paediatric Rheumatology, Sophia Children's Hospital, Erasmus Medical Centre, Rotterdam, The Netherlands.,Department of Paediatric Rheumatology, Alder Hey Children's Hospital, Liverpool
| | - Paul Brogan
- Department of Paediatric Rheumatology, University College London Great Ormond Street Institute of Child Health and Great Ormond St Hospital for Children NHS Foundation Trust, London, UK
| | - Seza Ozen
- Department of Paediatric Rheumatology, Hacettepe University, Ankara, Turkey
| | - Tadej Avcin
- Department of Paediatric Rheumatology, University Children's Hospital Ljubljana, Ljubljana, Slovenia
| | - Brigitte Bader-Meunier
- Department of Paediatric Rheumatology, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Pavla Dolezalova
- 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
| | - Brian M Feldman
- Department of Paediatric Rheumatology, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Isabelle Kone-Paut
- Department of Paediatric Rheumatology, Bicêtre University Hospital, APHP, University of Paris Sud, Paris, France
| | - Pekka Lahdenne
- Department of Paediatric Rheumatology, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
| | - Stephen D Marks
- Department of Paediatric Rheumatology, University College London Great Ormond Street Institute of Child Health and Great Ormond St Hospital for Children NHS Foundation Trust, London, UK
| | - Liza McCann
- Department of Paediatric Rheumatology, Alder Hey Children's Hospital, Liverpool
| | - Clarissa Pilkington
- Department of Paediatric Rheumatology, University College London Great Ormond Street Institute of Child Health and Great Ormond St Hospital for Children NHS Foundation Trust, London, UK
| | - Angelo Ravelli
- Department of Paediatric Rheumatology, Gaslini Children's Hospital, Genoa, Italy
| | - Annet van Royen
- Department of Paediatric Rheumatology, Wilhelmina Children's Hospital, Utrecht
| | - Yosef Uziel
- Meir Medical Center, Kfar Saba, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel
| | - Bas Vastert
- Department of Paediatric Rheumatology, Wilhelmina Children's Hospital, Utrecht
| | - Nico Wulffraat
- Department of Paediatric Rheumatology, Wilhelmina Children's Hospital, Utrecht
| | - Sylvia Kamphuis
- Department of Paediatric Rheumatology, Sophia Children's Hospital, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Michael W Beresford
- Department of Paediatric Rheumatology, Alder Hey Children's Hospital, Liverpool.,Institute of Translational Medicine, University of Liverpool, Liverpool, UK
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12
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Roitsch S, Gößwein S, Neurath MF, Leppkes M. Detection by flow cytometry of anti-neutrophil cytoplasmic antibodies in a novel approach based on neutrophil extracellular traps. Autoimmunity 2019; 51:288-296. [PMID: 30994385 DOI: 10.1080/08916934.2018.1527317] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Anti-neutrophil-cytoplasmic antibodies (ANCA) are auto-antibodies directed against components of neutrophil granulocytes and may be found in various inflammatory conditions, like small-vessel vasculitis or ulcerative colitis (UC). Routine ANCA screening is performed on ethanol-fixed neutrophils using indirect immunofluorescence technique. Yet, how neutrophil granule proteins become available to immunologic presentation is a matter of debate. In recent years, various studies have shown that neutrophils are able to extrude their chromatin decorated with granular proteins as neutrophil extracelullar traps (NETs). AIM We hypothesized that (I) ANCA immunoreactivity may be found on NETs and (II) NETs may serve as a useful tool in a novel approach for ANCA detection. METHODS Sera from patients suffering from either ANCA-associated vasculitis (n = 10), UC (n = 30) or sera from patients without diagnosed ANCA-associated diseases (n = 20), respectively, were subjected to indirect immunofluorescence and a newly developed method to detect ANCA by flow cytometry employing microbead technology. RESULTS ANCA-related immunofluorescence was readily detectable on ethanol-fixed NETs, establishing NETs as a structure carrying ANCA target antigens. Moreover, we observed that neutrophils form NETs in response to microbeads and stick to the surface of these beads. Using these NET-coated microbeads in flow cytometry, we were capable of reliably detecting p-ANCA, c-ANCA, and a-ANCA in tested patient sera. UC-related complex DNase-1-sensitive ANCA (NET-ANCA) antigens were also detected on NET-coated microbeads. CONCLUSION NET-coated microbeads may be commercially developed as a novel tool for automated ANCA screening assays using flow cytometry.
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Affiliation(s)
- Stefan Roitsch
- a Department of Internal Medicine 1 - Gastroenterology, Pneumology and Endocrinology , Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen , Erlangen , Germany
| | - Stefanie Gößwein
- a Department of Internal Medicine 1 - Gastroenterology, Pneumology and Endocrinology , Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen , Erlangen , Germany
| | - Markus F Neurath
- a Department of Internal Medicine 1 - Gastroenterology, Pneumology and Endocrinology , Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen , Erlangen , Germany
| | - Moritz Leppkes
- a Department of Internal Medicine 1 - Gastroenterology, Pneumology and Endocrinology , Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen , Erlangen , Germany
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13
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Andrade GC, Maia FCP, Mourão GF, Rosario PW, Calsolari MR. Antineutrophil cytoplasmic antibodies in patients treated with methimazole: a prospective Brazilian study. Braz J Otorhinolaryngol 2019; 85:636-641. [PMID: 30057255 PMCID: PMC9443009 DOI: 10.1016/j.bjorl.2018.05.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 05/28/2018] [Accepted: 05/28/2018] [Indexed: 10/28/2022] Open
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14
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Yang W, Peng Q, Guo Z, Wu H, Ding S, Chen Y, Zhao M. PtCo nanocubes/reduced graphene oxide hybrids and hybridization chain reaction-based dual amplified electrochemiluminescence immunosensing of antimyeloperoxidase. Biosens Bioelectron 2019; 142:111548. [PMID: 31400729 DOI: 10.1016/j.bios.2019.111548] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 07/26/2019] [Accepted: 07/28/2019] [Indexed: 11/24/2022]
Abstract
Antimyeloperoxidase (anti-MPO) is regarded as one of the most important circulating autoantibodies for anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAVs). Hence, it is crucial for highly sensitive detection of anti-MPO to monitor efficacy of AAVs in clinical diagnosis. Herein, a highly sensitive electrochemiluminescence (ECL) immunosensor for anti-MPO detection was constructed by combining reduced graphene oxide-supported PtCo nanocubes hybrids (PtCo@rGO) with hybridization chain reaction (HCR) as signal amplification. Multiple ECL luminophores (Dox-ABEI) prepared by cross-linking of N-(aminobutyl)-N-(ethylisoluminol) (ABEI) and doxorubicin (Dox) were intercalated into dsDNA products of HCR, achieving the effective immobilization of ECL luminophores to obtain strong ECL emission. Benefiting from the efficient catalytic activity of PtCo@rGO toward H2O2, the massive the superoxide radical (O2●-) were generated to further react with ABEI for ECL emission. Thus, the designed ECL immunoassay for anti-MPO detection exhibited excellent sensitivity of a concentration variation from 50 fg/mL to 1 ng/mL and a detection limit of 15.68 fg/mL. Importantly, this work proposed an enzyme-free ECL immunoassay with high sensitivity, excellent specificity for protein detection in clinical diagnosis.
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Affiliation(s)
- Wei Yang
- Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China
| | - Qiling Peng
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Zhen Guo
- Department of Clinical Laboratory, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Haiping Wu
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Shijia Ding
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Yongjian Chen
- Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China.
| | - Min Zhao
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
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15
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Damoiseaux J, Heijnen I, Van Campenhout C, Eriksson C, Fabien N, Herold M, van der Molen RG, Egner W, Patel D, Plaza-Lopez A, Radice A, de Sousa MJR, Viander M, Shoenfeld Y. An international survey on anti-neutrophil cytoplasmic antibodies (ANCA) testing in daily clinical practice. Clin Chem Lab Med 2019; 56:1759-1770. [PMID: 28710880 DOI: 10.1515/cclm-2017-0306] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Accepted: 05/29/2017] [Indexed: 12/22/2022]
Abstract
Abstract
Background:
Detection of anti-neutrophil cytoplasmic antibodies (ANCA) is important for the diagnosis of the ANCA-associated vasculitides (AAV). For AAV, especially ANCA directed against myeloperoxidase (MPO) and proteinase 3 (PR3) are most relevant. ANCA with less well-defined specificities may, however, also be detected in other inflammatory and non-inflammatory conditions.
Methods:
A questionnaire, initiated by the European Autoimmunity Standardisation Initiative (EASI), was used to gather information on methods and testing algorithms used for ANCA in clinical laboratories of 12 European countries (EASI survey).
Results:
Four hundred and twenty-nine responses were included in the EASI survey analysis which revealed differences within countries and between countries. Laboratories overall were poor in adherence to international consensus on ANCA testing. Substantial variation was observed with respect to the use of ANCA indirect immunofluorescence (IIF) in the algorithm, application of distinct methods for MPO- and PR3-ANCA, the daily availability of new ANCA results, and interpretation of test results.
Conclusions:
Awareness of these differences may stimulate further harmonization and standardization of ANCA testing. This may be promoted by an update of the international ANCA consensus and the introduction of international standards.
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Affiliation(s)
- Jan Damoiseaux
- Central Diagnostic Laboratory, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands
| | - Ingmar Heijnen
- Medical Immunology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland
| | | | - Catharina Eriksson
- Department of Clinical Immunology/Microbiology, Umeå University, Umeå, Sweden
| | - Nicole Fabien
- Department of Immunology, UF Autoimmunity, Hospices Civils de Lyon, CHLS, Pierre-Benite, France
| | - Manfred Herold
- Department of Internal Medicine/Rheumatology unit, Innsbruck Medical University, Innsbruck, Austria
| | - Renate G van der Molen
- Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - William Egner
- UK NEQAS Immunology, Immunochemistry and Allergy, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Dina Patel
- UK NEQAS Immunology, Immunochemistry and Allergy, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Aresio Plaza-Lopez
- Department of Immunology, Hospital Universitario Puerta de Hierro, Majadahonda, Spain
| | - Antonella Radice
- Microbiology Institute, San Carlo Borromeo Hospital, Milan, Italy - on behalf of the Italian Forum on Autoimmune Disease Research (FIRMA)
| | - Marie José Rego de Sousa
- Immunopathology and Autoimmunity Department, Centro de Medicina Laboratorial Germano de Sousa, Lisbon, Portugal
| | - Markku Viander
- Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland
| | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
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16
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Csernok E. The Diagnostic and Clinical Utility of Autoantibodies in Systemic Vasculitis. Antibodies (Basel) 2019; 8:antib8020031. [PMID: 31544837 PMCID: PMC6640716 DOI: 10.3390/antib8020031] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 04/14/2019] [Accepted: 04/16/2019] [Indexed: 12/26/2022] Open
Abstract
Considerable progress has been made in understanding the role of autoantibodies in systemic vasculitides (SV), and consequently testing for anti-neutrophil cytoplasmic antibodies (ANCA), anti-glomerular basement membrane antibodies (anti-GBM), and anti-C1q antibodies is helpful and necessary in the diagnosis, prognosis, and monitoring of small-vessel vasculitis. ANCA-directed proteinase 3 (PR3-) or myeloperoxidase (MPO-) are sensitive and specific serologic markers for ANCA-associated vasculitides (AAV), anti-GBM antibodies are highly specific for the patients with anti-GBM antibody disease (formerly Goodpasture’s syndrome), and autoantibodies to C1q are characteristic of hypocomlementemic urticarial vasculitis syndrome (HUVS; anti-C1q vasculitis). The results of a current EUVAS study have led to changes in the established strategy for the ANCA testing in small-vessel vasculitis. The revised 2017 international consensus recommendations for ANCA detection support the primary use PR3- and MPO-ANCA immunoassays without the categorical need for additional indirect immunofluorescence (IIF). Interestingly, the presence of PR3- and MPO-ANCA have led to the differentiation of distinct disease phenotype of AAV: PR3-ANCA-associated vasculitis (PR3-AAV), MPO-ANCA-associated vasculitis (MPO-AAV), and ANCA-negative vasculitis. Further studies on the role of these autoantibodies are required to better categorize and manage appropriately the patients with small-vessel vasculitis and to develop more targeted therapy.
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Affiliation(s)
- Elena Csernok
- Department of Internal Medicine, Rheumatology and Immunology, Vasculitis-Center Tübingen-Kirchheim, Medius Klinik Kirchheim, University of Tübingen, 73230 Kirchheim-Teck, Germany.
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17
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Carubbi F, Alunno A, Cipriani P, Bistoni O, Scipioni R, Liakouli V, Ruscitti P, Berardicurti O, Di Bartolomeo S, Gerli R, Giacomelli R. Laboratory Assessment of Patients with Suspected Rheumatic Musculoskeletal Diseases: Challenges and Pitfalls. Curr Rheumatol Rev 2019; 15:27-43. [PMID: 29557752 DOI: 10.2174/1573397114666180320113603] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 03/14/2018] [Accepted: 03/15/2018] [Indexed: 11/22/2022]
Abstract
Current patient care in rheumatology relies primarily on a combination of traditional clinical assessment and standard laboratory tests. Investigators seek to discover new biomarkers and novel technologies to boost the research in this field. Mechanistic biomarkers such as cytokines, cell types, antibodies, signaling molecules, are rooted in the mechanism underlying the disease and can guide the clinical management of the disease. Conversely, descriptive biomarkers are byproducts of the disease process, depict the state of a disease but are not involved in its pathogenesis. In this article, we reviewed the field of common laboratory biomarkers in rheumatology, highlighting both their descriptive or mechanistic value as well as their role in clinical practice.
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Affiliation(s)
- Francesco Carubbi
- Rheumatology Unit, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, AQ, Italy.,Department of Medicine, ASL1 Avezzano-Sulmona-L'Aquila, L'Aquila, AQ, Italy
| | - Alessia Alunno
- Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, PG, Italy
| | - Paola Cipriani
- Rheumatology Unit, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, AQ, Italy
| | - Onelia Bistoni
- Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, PG, Italy
| | - Rosa Scipioni
- Department of Medicine, ASL1 Avezzano-Sulmona-L'Aquila, L'Aquila, AQ, Italy
| | - Valiki Liakouli
- Rheumatology Unit, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, AQ, Italy
| | - Piero Ruscitti
- Rheumatology Unit, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, AQ, Italy
| | - Onorina Berardicurti
- Rheumatology Unit, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, AQ, Italy
| | - Salvatore Di Bartolomeo
- Rheumatology Unit, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, AQ, Italy
| | - Roberto Gerli
- Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, PG, Italy
| | - Roberto Giacomelli
- Rheumatology Unit, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, AQ, Italy
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18
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van Beers JJBC, Vanderlocht J, Roozendaal C, Damoiseaux J. Detection of Anti-neutrophil Cytoplasmic Antibodies (ANCA) by Indirect Immunofluorescence. Methods Mol Biol 2019; 1901:47-62. [PMID: 30539567 DOI: 10.1007/978-1-4939-8949-2_4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
The eventual presence of anti-neutrophil cytoplasmic antibodies (ANCA) can initially be screened with indirect immunofluorescence (IIF). The majority of laboratories that facilitate ANCA testing use commercial kits. Although in-house assays are not encouraged in routine clinical laboratories, knowledge on the methodological aspects of the assay remains of importance. These aspects include choice of substrate, choice of fixative, staining procedure, and interpretation procedure. In this paper details on the methodology are provided and discussed in the context of the clinical application.
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Affiliation(s)
- J J B C van Beers
- Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - J Vanderlocht
- Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - C Roozendaal
- Department of Laboratory Medicine, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | - J Damoiseaux
- Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, The Netherlands.
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Holding S. Challenges and opportunities from the revised international consensus on ANCA testing. Ann Clin Biochem 2019; 56:4-6. [DOI: 10.1177/0004563218778303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Stephen Holding
- Immunology Department, Hull Royal Infirmary, Hull, UK
- Medicine Department, Hull York Medical School, Hull, UK
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Berden AE, Wester Trejo MAC, Bajema IM. Investigations in systemic vasculitis - The role of renal pathology. Best Pract Res Clin Rheumatol 2018; 32:83-93. [PMID: 30526900 DOI: 10.1016/j.berh.2018.10.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 10/18/2018] [Accepted: 10/22/2018] [Indexed: 11/29/2022]
Abstract
ANCA-associated vasculitis (AAV) describes a group of small-vessel vasculitides with frequent renal involvement. The first description of these conditions can be traced back to the 19th-century paper on necrotizing vasculitis by Kussmaul and Maier. Since then, our understanding of the pathogenesis has improved and the histopathological lesions have been described in detail. Characteristic histologic lesions in ANCA-associated glomerulonephritis (AAGN) are fibrinoid necrosis and crescents, often accompanied by tubulointerstitial inflammation. The discovery of ANCAs has not rendered renal biopsies obsolete in the diagnostic process. Currently, renal biopsies remain the gold standard for the diagnosis of AAV in conjunction with ANCA serology. In addition to diagnosis, renal biopsies are useful for patient prognosis. The evaluation of renal histological samples from patients with new-onset AAV who participated in clinical trials led to the proposal of the histopathological classification for AAGN. The prognostic value of this classification continues to be validated and an update is expected soon.
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Affiliation(s)
- Annelies E Berden
- Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands
| | | | - Ingeborg M Bajema
- Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
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Abu-Freha N, Badarna W, Sigal-Batikoff I, Abu Tailakh M, Etzion O, Elkrinawi J, Segal A, Mushkalo A, Fich A. ASCA and ANCA among Bedouin Arabs with inflammatory bowel disease, the frequency and phenotype correlation. BMC Gastroenterol 2018; 18:153. [PMID: 30342474 PMCID: PMC6195956 DOI: 10.1186/s12876-018-0884-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Accepted: 10/14/2018] [Indexed: 12/28/2022] Open
Abstract
Background Serological markers used for diagnostic purposes and disease stratification in inflammatory bowel disease. We aimed to investigate the frequency of ASCA and ANCA among Arab Bedouin IBD patients and its relationship to disease phenotype and course. Methods From cohort of 68, 25 Crohn’s disease (CD) and 25 Ulcerative colitis (UC) patients were recruited (72%). ASCA IgG was determined by ELISA assay. Immunofluorescence analysis of ANCA was performed. Results The IgG ASCA was detected in 13 (52%) of the CD patients and in three (12%) UC patients. The prevalence of ANCA among UC patients was positive with 76%, sub-grouped, atypical ANCA in 9 patients (36%), pANCA in six patients (24%) and cANCA in 4 patients (16%). The detection of ASCA among CD patients was found not to be a reliable predictor of young age at diagnosis, gender, ileal involvement, anti-TNF treatment or surgery. UC patients with positive ANCA were younger, mean age 40.2 ± 11.9 compared with 57.3 ± 21.2 (p = 0.03), and diagnosed at a younger age, 29.2 ± 11.8 compared with 43.5 ± 15.3 (p = 0.05). Conclusion The frequency of ASCA among Bedouin CD patients and ANCA among UC patients was high, however ASCA was not found to have a predictive value for disease phenotype or course. Positive ANCA in UC patients was predictive for younger age and age at diagnosis.
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Affiliation(s)
- Naim Abu-Freha
- The Institute of Gastroenterology and Hepatology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 151, 84101, Beer-Sheva, Israel.
| | - Wafi Badarna
- Internal Medicine ward E, Soroka University Medical Center, Beer-Sheva, Israel
| | - Ina Sigal-Batikoff
- The Institute of Gastroenterology and Hepatology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 151, 84101, Beer-Sheva, Israel.,Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | | | - Ohad Etzion
- The Institute of Gastroenterology and Hepatology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 151, 84101, Beer-Sheva, Israel
| | - Jaber Elkrinawi
- The Institute of Gastroenterology and Hepatology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 151, 84101, Beer-Sheva, Israel
| | - Arik Segal
- The Institute of Gastroenterology and Hepatology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 151, 84101, Beer-Sheva, Israel
| | - Alex Mushkalo
- The Institute of Gastroenterology and Hepatology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 151, 84101, Beer-Sheva, Israel
| | - Alex Fich
- The Institute of Gastroenterology and Hepatology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 151, 84101, Beer-Sheva, Israel
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Crisford H, Sapey E, Stockley RA. Proteinase 3; a potential target in chronic obstructive pulmonary disease and other chronic inflammatory diseases. Respir Res 2018; 19:180. [PMID: 30236095 PMCID: PMC6149181 DOI: 10.1186/s12931-018-0883-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Accepted: 09/06/2018] [Indexed: 12/15/2022] Open
Abstract
Chronic Obstructive Pulmonary Disease (COPD) is a common, multifactorial lung disease which results in significant impairment of patients' health and a large impact on society and health care burden. It is believed to be the result of prolonged, destructive neutrophilic inflammation which results in progressive damage to lung structures. During this process, large quantities of neutrophil serine proteinases (NSPs) are released which initiate the damage and contribute towards driving a persistent inflammatory state.Neutrophil elastase has long been considered the key NSP involved in the pathophysiology of COPD. However, in recent years, a significant role for Proteinase 3 (PR3) in disease development has emerged, both in COPD and other chronic inflammatory conditions. Therefore, there is a need to investigate the importance of PR3 in disease development and hence its potential as a therapeutic target. Research into PR3 has largely been confined to its role as an autoantigen, but PR3 is involved in triggering inflammatory pathways, disrupting cellular signalling, degrading key structural proteins, and pathogen response.This review summarises what is presently known about PR3, explores its involvement particularly in the development of COPD, and indicates areas requiring further investigation.
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Affiliation(s)
- Helena Crisford
- Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham, B15 2GW, UK.
- Institute of Inflammation and Ageing, College of Medical and Dental Sciences, Centre for Translational Inflammation Research, University of Birmingham Research Laboratories, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2WB, UK.
| | - Elizabeth Sapey
- Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham, B15 2GW, UK
| | - Robert A Stockley
- University Hospital Birmingham NHS Foundation Trust, Edgbaston, Birmingham, B15 2GW, UK
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23
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Savige J, Trevisin M, Pollock W. Testing and reporting antineutrophil cytoplasmic antibodies (ANCA) in treated vasculitis and non-vasculitic disease. J Immunol Methods 2018; 458:1-7. [DOI: 10.1016/j.jim.2018.02.016] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 02/22/2018] [Accepted: 02/22/2018] [Indexed: 12/23/2022]
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Mendez-Rayo T, Ochoa-Zárate L, Posso-Osorio I, Ortiz E, Naranjo-Escobar J, Tobón GJ. Interpretation of autoantibodies in rheumatological diseases. ACTA ACUST UNITED AC 2018. [DOI: 10.1016/j.rcreue.2019.01.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Csernok E, Mahrhold J, Hellmich B. Anti-neutrophil cytoplasm antibodies (ANCA): Recent methodological advances-Lead to new consensus recommendations for ANCA detection. J Immunol Methods 2018; 456:1-6. [PMID: 29395165 DOI: 10.1016/j.jim.2018.01.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Accepted: 01/22/2018] [Indexed: 12/13/2022]
Abstract
The current practice for detection of anti-neutrophil cytoplasm antibodies (ANCA) directed against proteinase 3 (PR3) and myeloperoxidase (MPO) has been screening by indirect immunofluorescence (IIF) followed by an antigen specific tests for PR3- and MPO-ANCA. However, ANCA diagnostics have undergone many technical developments that have affected the 1999 international consensus recommendations, and lead to a revision of the existing ANCA detection strategy. Recent European multicentre studies have compared the diagnostic performance of various ANCA detection methods and demonstrated that PR3- and MPO-ANCA immunoassays yielded the highest diagnostic accuracy. New guidelines for ANCA testing have been developed based on these data. According to the revised 2017 international consensus recommendations, testing for ANCA in small vessel vasculitis can be done by PR3- and MPO-ANCA immunoassays, without the categorical need for IIF. Thus, IIF can be discarded completely, or can be used as confirmation assays instead a screening test. Clearly, though, the new testing strategy for ANCA in vasculitis must identify the ANCA target antigen, as PR3- and MPO-ANCA serotype correlate well with disease expression. Furthermore, recent studies have shown that AAV can be classified based on ANCA serotype, since PR3- and MPO-ANCA- diseases are strongly associated with distinguishable genetic alleles, different clinical and histological features. ANCA presence and the antigen specificity also may have important value as a prognostic factor and may serve as a guide for immunosuppressive therapy. In the current review, we summarize the novelties in ANCA testing, present the 2017 revised international consensus on ANCA testing in vasculitis, evaluate the diagnostic significance of ANCA, and discuss the role of ANCA serotypes in the diagnostic work-up of patients with AAV.
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Affiliation(s)
- Elena Csernok
- Department of Internal Medicine, Rheumatology and Immunology, Vasculitis-Center Tübingen-Kirchheim, Medius Klinik Kirchheim, University of Tübingen, Kirchheim-Teck, Germany.
| | - Juliane Mahrhold
- Department of Internal Medicine, Rheumatology and Immunology, Vasculitis-Center Tübingen-Kirchheim, Medius Klinik Kirchheim, University of Tübingen, Kirchheim-Teck, Germany.
| | - Bernhard Hellmich
- Department of Internal Medicine, Rheumatology and Immunology, Vasculitis-Center Tübingen-Kirchheim, Medius Klinik Kirchheim, University of Tübingen, Kirchheim-Teck, Germany.
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Hellmich B. [Current guidelines on ANCA-associated vasculitides : Common features and differences]. Z Rheumatol 2017; 76:133-142. [PMID: 27848024 DOI: 10.1007/s00393-016-0223-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The results of a number of prospective randomized controlled clinical trials have led to changes in established strategies for the treatment of antineutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV) in recent years. Since 2014, a total of 4 scientific societies and study groups have systematically reviewed the new data and have formulated evidence-based recommendations for the management of AAV based on the analysis. These recommendations contain information on diagnosis, treatment (induction and maintenance), supportive care and monitoring of disease activity and resulting damage. This review compares the recently published recommendations of the German Society of Rheumatology (Deutschen Gesellschaft für Rheumatologie, DGRh), the European League Against Rheumatism (EULAR)/European Renal Association (ERA), the British Society of Rheumatology (BSR) and the Canadian Vasculitis Research Network (CanVasc). The comparative analysis reveals a high level of agreement on numerous topics but also shows some minor and even a few major differences in the respective recommended approach to diagnosis and treatment of AAV. Divergent recommendations predominantly exist in areas with little scientific evidence from clinical studies. Furthermore, some differences result from different interpretation of existing data or are influenced by characteristic features of the respective national healthcare system.
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Affiliation(s)
- B Hellmich
- Vaskulitiszentrum Süd, Klinik für Innere Medizin, Rheumatologie und Immunologie, Klinik Kirchheim, Akademisches Lehrkrankenhaus der Universität Tübingen, Eugenstr. 3, 73230, Kirchheim u. Teck, Deutschland.
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27
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Abstract
ANCA vasculitis has an associated autoimmune response that produces ANCAs that induce distinct pathologic lesions. Pauci-immune necrotizing and crescentic GN is a frequent component of ANCA vasculitis. ANCA vasculitis is associated with ANCA specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA). A diagnosis of ANCA vasculitis should always specify the serotype as MPO-ANCA positive, PR3-ANCA positive, or ANCA-negative. To fully characterize a patient, the serotype also should be accompanied by the clinicopathologic variant if this can be determined: microscopic polyangiitis, granulomatosis with polyangiitis (Wegener), eosinophilic granulomatosis with polyangiitis (Churg-Strauss), or renal-limited vasculitis. ANCA vasculitis is most prevalent in individuals >50 years old. There are racial/ethnic and geographic influences on the prevalence, serotype frequencies, and clinicopathologic phenotypes. There is clinical, in vitro, and animal model evidence that ANCAs cause disease by activating neutrophils to attack small vessels. Immunomodulatory and immunosuppressive therapies are used to induce remission, maintain remission, and treat relapses. Over recent years, there have been major advances in optimizing treatment by minimizing toxic therapy and utilizing more targeted therapy.
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Affiliation(s)
- J Charles Jennette
- Department of Pathology and Laboratory Medicine, Department of Medicine, and Kidney Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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Évaluation de la pertinence des demandes d’anticorps anticytoplasme des polynucléaires neutrophiles : étude rétrospective menée au sein du centre hospitalier universitaire de Bordeaux. Rev Med Interne 2017; 38:656-662. [DOI: 10.1016/j.revmed.2017.06.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2016] [Revised: 04/25/2017] [Accepted: 06/01/2017] [Indexed: 12/15/2022]
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Givaudan M, Vandergheynst F, Stordeur P, Ocmant A, Melot C, Gangji V, Soyfoo MS. Value of non-identified ANCA (non-PR3, non-MPO) in the diagnosis of granulomatosis with polyangiitis (Wegener's granulomatosis). Acta Clin Belg 2017; 72:313-317. [PMID: 28067125 DOI: 10.1080/17843286.2016.1275374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
OBJECTIVE Determine the frequency of granulomatosis with polyangiitis (GPA) associated with non-identified ANCA (non-MPO, non-PR3 ANCA) and secondarily compare their clinic with GPA associated with MPO-positive or PR3-positive ANCA. METHODS In a monocentric retrospective observational study, clinical data of 398 patients with non-identified ANCA (titer of ANCA at least 1/80 by immunofluorescence on ethanol fixed PMN) was gathered over a period of 6 years. GPA patients from this population were compared with GPA patients with identified ANCA on the basis of clinical, biological, immunological and histological features. RESULTS The most common diseases associated with non-identified ANCA were inflammatory bowel diseases accounting for 17% of diseases. GPA accounted for only 1.8% of cases. There were no significant differences in terms of clinical and histological characteristics between GPA with non-identified ANCA and GPA with identified ANCA, but significantly higher CRP levels were observed in GPA patients with identified ANCA (p = 0.005). Localized disease (ear, nose and throat and/or lung involvement without any other systemic involvement) was more frequent in the group of GPA with nonidentified ANCA (p = 0.047) as compared to GPA with identified ANCA. This explains that the former group of patients was less frequently treated by cyclophosphamide than the latter (p = 0.016). CONCLUSION GPA with non-MPO, non-PR3 ANCAs is relatively rare. Our study suggests that GPA with nonidentified ANCA differs from GPA with identified ANCA by the frequency of localized forms.
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Affiliation(s)
- Mélanie Givaudan
- Department of Rheumatology, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Frédéric Vandergheynst
- Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Patrick Stordeur
- Department of Immunobiology Clinic, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Annick Ocmant
- Department of Immunobiology Clinic, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Christian Melot
- Department of Emergency, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Valérie Gangji
- Department of Rheumatology, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Muhammad S. Soyfoo
- Department of Rheumatology, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
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30
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Bossuyt X, Cohen Tervaert JW, Arimura Y, Blockmans D, Flores-Suárez LF, Guillevin L, Hellmich B, Jayne D, Jennette JC, Kallenberg CGM, Moiseev S, Novikov P, Radice A, Savige JA, Sinico RA, Specks U, van Paassen P, Zhao MH, Rasmussen N, Damoiseaux J, Csernok E. Position paper: Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat Rev Rheumatol 2017; 13:683-692. [PMID: 28905856 DOI: 10.1038/nrrheum.2017.140] [Citation(s) in RCA: 252] [Impact Index Per Article: 31.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Anti-neutrophil cytoplasmic antibodies (ANCAs) are valuable laboratory markers used for the diagnosis of well-defined types of small-vessel vasculitis, including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). According to the 1999 international consensus on ANCA testing, indirect immunofluorescence (IIF) should be used to screen for ANCAs, and samples containing ANCAs should then be tested by immunoassays for proteinase 3 (PR3)-ANCAs and myeloperoxidase (MPO)-ANCAs. The distinction between PR3-ANCAs and MPO-ANCAs has important clinical and pathogenic implications. As dependable immunoassays for PR3-ANCAs and MPO-ANCAs have become broadly available, there is increasing international agreement that high-quality immunoassays are the preferred screening method for the diagnosis of ANCA-associated vasculitis. The present Consensus Statement proposes that high-quality immunoassays can be used as the primary screening method for patients suspected of having the ANCA-associated vaculitides GPA and MPA without the categorical need for IIF, and presents and discusses evidence to support this recommendation.
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Affiliation(s)
- Xavier Bossuyt
- Department of Microbiology and Immunology, University of Leuven and Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Herestraat 49, 3000 Leuven, Belgium
| | | | - Yoshihiro Arimura
- Kichijoji Asahi Hospital, 11-30-12 Kichijoji Honcho, Musashino, Tokyo 181-8611, Japan
| | - Daniel Blockmans
- Clinical Department of General Internal Medicine, Research Department of Microbiology and Immunology and Laboratory of Clinical Infectious and Inflammatory Disorders, University Hospitals Leuven, Leuven, Herestraat 49, 3000 Leuven, Belgium
| | - Luis Felipe Flores-Suárez
- Primary Systemic Vasculitides Clinic, Instituto Nacional de Enfermedades Respiratorias, Calzada de Tlalpan 4502, Colonia Sección XVI, CP 14080, Mexico City, Mexico
| | - Loïc Guillevin
- National Referral Centre for Necrotizing Vasculitides and Systemic Sclerosis, Université Paris Descartes, Hôpital Cochin, L'Assistance Publique-Hôpitaux de Paris, 27 Rue du Faubourg Saint-Jacques, Paris 75014, France
| | - Bernhard Hellmich
- Department of Internal Medicine, Rheumatology and Immunology, Vasculitis-Centre Tübingen-Kirchheim, Medius Klinik Kirchheim, University of Tübingen, Eugenstrasse 3, 73230 Kirchheim unter Teck, Germany
| | - David Jayne
- Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0SP, UK
| | - J Charles Jennette
- Department of Pathology and Laboratory Medicine, University of North Carolina, 160 Medical Drive, Chapel Hill, North Carolina 27599, USA
| | - Cees G M Kallenberg
- Department of Rheumatology and Clinical Immunology, AA21, University Medical Centre Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, Netherlands
| | - Sergey Moiseev
- Clinic of Nephrology, Internal and Occupational Diseases, Sechenov First Moscow State Medical University, Rossolimo, 11/5, Moscow 119435, Russia
| | - Pavel Novikov
- Clinic of Nephrology, Internal and Occupational Diseases, Sechenov First Moscow State Medical University, Rossolimo, 11/5, Moscow 119435, Russia
| | - Antonella Radice
- Microbiology and Virology Institute, ASST Santi Paolo e Carlo, San Carlo Borromeo Hospital, Via Pio II 3, 20153 Milan, Italy
| | - Judith Anne Savige
- Department of Medicine, Melbourne Health, The University of Melbourne, Grattan Street, Parkville, Melbourne VIC 3050, Australia
| | - Renato Alberto Sinico
- Department of Medicine and Surgery, Università degli Studi di Milano-Bicocca, Via Cadore, 48, 20900 Monza MB, Italy
| | - Ulrich Specks
- Division of Pulmonary & Critical Medicine, Mayo Clinic, Rochester, 200 First Street, Rochester, Minnesota 55905, USA
| | - Pieter van Paassen
- Department of Internal Medicine, Section Nephrology and Immunology, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX Maastricht, Netherlands
| | - Ming-Hui Zhao
- Renal Division, Peking University First Hospital; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China; Peking-Tsinghua Centre for Life Sciences; 8 Xishiku Street, Xichengqu, Beijing Shi, China
| | - Niels Rasmussen
- Department of Autoimmunology and Biomarkers, Statens Seruminstitut, Artillerivej 5, 2300 Copenhagen S, Denmark
| | - Jan Damoiseaux
- Central Diagnostic Laboratory, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX Maastricht, Netherlands
| | - Elena Csernok
- Department of Internal Medicine, Rheumatology and Immunology, Vasculitis-Centre Tübingen-Kirchheim, Medius Klinik Kirchheim, University of Tübingen, Eugenstrasse 3, 73230 Kirchheim unter Teck, Germany
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31
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Sun Q, Calderon B, Zhao Z. Discrepancies between two immunoassays for the determination of MPO and PR3 autoantibodies. Clin Chim Acta 2017; 470:93-96. [PMID: 28495147 DOI: 10.1016/j.cca.2017.05.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Revised: 04/21/2017] [Accepted: 05/07/2017] [Indexed: 11/17/2022]
Abstract
BACKGROUND Testing for autoantibodies to myeloperoxidase (MPO) and proteinase 3 (PR3) is part of anti-neutrophil cytoplasmic antibodies (ANCA) test that aids the diagnosis of a number of autoimmune diseases including small-vessel vasculitis. We characterized the differences between two automated immunoassays at three facilities for measuring MPO- and PR3-ANCA autoantibodies. METHODS 117 serum samples were analyzed for MPO and PR3 autoantibodies. The INOVA QUANTA Lite® IgG assay (INOVA Diagnostics) were performed at two facilities and the Bio-Plex® 2200 Vasculitis Panel (Bio-Rad) were performed at a third reference lab. The results were compared both qualitatively (between INOVA QUANTA Lite® and Bio-Plex® methods) and quantitatively (between two sites performing INOVA QUANTA Lite® assays). RESULTS Comparison of the INOVA QUNATA Lite® assays at two different facilities (n=36) demonstrated high concordance (97.2% for MPO and 94.4% for PR3) and quantitative correlation (R2=0.973 for MPO and R2=0.935 for PR3). Conversely, INOVA QUNATA Lite® and Bio-Plex® methods showed poor concordance at 70.4% for MPO (n=81; 95% CI: 59.7% to 79.2%) and at 76.5% for PR3 (n=81; 95% CI: 66.2% to 84.4%). CONCLUSION This study demonstrated low concordance between two methods for MPO-ANCA and PR3-ANCA measurements. Given the discrepancies, the performance of different autoantibody immunoassay methods should be taken into consideration when evaluating MPO-ANCA and PR3-ANCA results.
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Affiliation(s)
- Qian Sun
- NIH Clinical Center, Department of Laboratory Medicine, Bethesda, MD, USA
| | | | - Zhen Zhao
- NIH Clinical Center, Department of Laboratory Medicine, Bethesda, MD, USA.
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32
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Anwar S, Karim MY. Update on systemic vasculitides. J Clin Pathol 2017; 70:476-482. [PMID: 28377447 DOI: 10.1136/jclinpath-2016-203875] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 02/08/2017] [Accepted: 02/23/2017] [Indexed: 02/02/2023]
Abstract
Management of systemic vasculitis has been revolutionised over the last decade with the introduction of targeted biological agents. With an increase in both the prevalence and the recognition of vasculitis as well as the high cost of these agents, it is important to ensure their most optimal utilisation. The goals of vasculitis therapy include the induction and maintenance of remissions, preventing relapses, reducing the toxicity of therapy with the aim of reducing morbidity and mortality as well as improving the quality of life of those afflicted. This review focuses on the recent advances in the diagnosis, surveillance and treatment of these conditions.
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Affiliation(s)
- Siddiq Anwar
- Department of Medicine, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
| | - M Yousuf Karim
- Immunology Department, Frimley Park Hospital, Frimley, UK
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33
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Phatak S, Aggarwal A, Agarwal V, Lawrence A, Misra R. Antineutrophil cytoplasmic antibody (ANCA) testing: Audit from a clinical immunology laboratory. Int J Rheum Dis 2017; 20:774-778. [PMID: 27457216 DOI: 10.1111/1756-185x.12926] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/13/2023]
Abstract
AIM Anti-neutrophil cytoplasmic antibodies (ANCA) are associated with small vessel vasculitis now termed 'ANCA associated vasculitis' (AAV). ANCAs are reported in diverse diseases where they have no clinical utility. We carried out an audit in a clinical immunology laboratory and assessed if use of ordering practices could have improved utility of ANCA. METHODS All samples received for ANCA testing during 2014 were tested by indirect immunofluorescence (IIF) and automated enzyme-linked immunosorbent assay (ELISA). Clinical records of all samples positive by one or more assays were retrieved. We assessed the effect of applying proposed test ordering guidelines on performance of the tests. RESULTS Of 1590 samples, 108 (6.8%) had a positive result by at least one method. IIF showed perinuclear pattern in 72 (21 were antinuclear antibody positive), cytoplasmic in 22, six had atypical pattern and eight were negative. By ELISA anti-myeloperoxidase antibodies were present in 33 samples, anti-proteinase 3 in 24, while five sera had both antibodies. ELISA and IIF were concordant in 45 samples. Twenty-seven patients had AAV of which 23 were both ELISA and IIF positive. Among these 27 with AAV all had at least one ordering criteria, while in 81 patients without AAV but with positive test, 38 had no ordering criteria. CONCLUSION Reduction in false positive can be achieved by considering only those samples as ANCA positive that test positive both on IIF and ELISA and by following ordering guidelines before requesting ANCA testing, and by use of ordering criteria by clinicians.
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Affiliation(s)
- Sanat Phatak
- Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Amita Aggarwal
- Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Vikas Agarwal
- Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Able Lawrence
- Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Ramnath Misra
- Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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Hov JR, Boberg KM, Taraldsrud E, Vesterhus M, Boyadzhieva M, Solberg IC, Schrumpf E, Vatn MH, Lie BA, Molberg Ø, Karlsen TH. Antineutrophil antibodies define clinical and genetic subgroups in primary sclerosing cholangitis. Liver Int 2017; 37:458-465. [PMID: 27558072 DOI: 10.1111/liv.13238] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2016] [Accepted: 08/18/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS The strongest genetic risk factors in primary sclerosing cholangitis (PSC) are encoded in the HLA complex. Antineutrophil cytoplasmic antibodies (ANCA) have been reported in up to 94% of PSC patients, but their clinical significance and immunogenetic basis are ill defined. We aimed to characterize clinical and genetic associations of ANCA in PSC. METHODS Antineutrophil cytoplasmic antibodies were analysed with indirect immunofluorescence in 241 Norwegian PSC patients. HLA-B and HLA-DRB1 genotyping was performed in the patients and in 368 healthy controls. Data on perinuclear ANCA (pANCA) and HLA-DRB1 were available from 274 ulcerative colitis (UC) patients without known liver disease. RESULTS Antineutrophil cytoplasmic antibodies were found in 193 (80%) of the PSC patients, with pANCA in 169 (70%). ANCA-positive patients were younger than ANCA negative at diagnosis of PSC and had a lower frequency of biliary cancer (9% vs 19%, P=.047). There were no differences between PSC patients with and without inflammatory bowel disease. Genetically, the strong PSC risk factors HLA-B*08 (frequency in healthy 13%) and DRB1*03 (14%) were more prevalent in ANCA-positive than -negative patients (43% vs 25%, P=.0012 and 43% vs 25%, P=.0015 respectively). The results were similar when restricting the analysis to pANCA-positive patients. In UC patients without liver disease, HLA-DRB1*03 was more prevalent in pANCA-positive compared with -negative patients (P=.03). CONCLUSIONS Antineutrophil cytoplasmic antibodies identified PSC patients with particular clinical and genetic characteristics, suggesting that ANCA may mark a clinically relevant pathogenetic subgroup in the PSC-UC disease spectrum.
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Affiliation(s)
- Johannes R Hov
- Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.,Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Section of Gastroenterology, Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.,Division of Surgery, Inflammatory Medicine and Transplantation, Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.,K.G.Jebsen Inflammation Research Centre, Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Kirsten M Boberg
- Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.,Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Section of Gastroenterology, Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Eli Taraldsrud
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,K.G.Jebsen Inflammation Research Centre, Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Mette Vesterhus
- Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.,National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
| | - Maria Boyadzhieva
- Clinical Center of Endocrinology, Medical University Sofia, Sofia, Bulgaria
| | - Inger Camilla Solberg
- Division of Medicine, Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo, Norway
| | - Erik Schrumpf
- Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.,Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Morten H Vatn
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,EpiGen Institute, Campus AHUS, Akershus University Hospital, Nordbyhagen, Norway
| | - Benedicte A Lie
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,K.G.Jebsen Inflammation Research Centre, Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Øyvind Molberg
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Rheumatology Unit, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Tom H Karlsen
- Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.,Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Section of Gastroenterology, Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.,Division of Surgery, Inflammatory Medicine and Transplantation, Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.,K.G.Jebsen Inflammation Research Centre, Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Csernok E, Kempiners N, Hellmich B. [Paradigm shift in ANCA diagnostics : New international consensus recommendations]. Z Rheumatol 2017; 76:143-148. [PMID: 28058500 DOI: 10.1007/s00393-016-0240-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
BACKGROUND Up to now indirect immunofluorescence (IIF) followed by an antigen-specific assay specific for proteinase 3 (PR3) or myeloperoxidase (MPO) has been the standard method for the detection of antineutrophil cytoplasmic antibodies (ANCA). The development of more sensitive and highly specific PR3-ANCA and MPO-ANCA immunoassays for the diagnosis of ANCA-associated vasculitis (AAV) has raised doubts about the two-stage diagnostic strategy currently recommended for ANCA detection. OBJECTIVE Presentation and discussion of the new international consensus recommendations on ANCA testing in AAV. METHODS This article presents the new guidelines for ANCA testing that have been developed based on the results of a recent large multicenter study by the European Vasculitis Society (EUVAS). The draft of the author committee was revised by each contributor and subsequently distributed to 12 experts on 4 continents. After further revision the final document was returned for ratification and submitted for publication. RESULTS/CONCLUSION The current study results confirm the superiority of the diagnostic value of antigen-specific immunoassays compared to IIF. The current consensus recommendations support the primary use of PR3-ANCA and MPO-ANCA immunoassays for diagnostic evaluation of patients with AAV without the categorical need for additional IIF.
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Affiliation(s)
- E Csernok
- Referenzlabor für Vaskulitis-Immundiagnostik, Vaskulitiszentrum Süd, Klinik für Innere Medizin, Rheumatologie und Immunologie, Kreiskliniken Esslingen gGmbH, Klinik Kirchheim, Akademisches Lehrkrankenhaus der Universität Tübingen, Eugenstr. 3, 73230, Kirchheim unter Teck, Deutschland.
| | - N Kempiners
- Referenzlabor für Vaskulitis-Immundiagnostik, Vaskulitiszentrum Süd, Klinik für Innere Medizin, Rheumatologie und Immunologie, Kreiskliniken Esslingen gGmbH, Klinik Kirchheim, Akademisches Lehrkrankenhaus der Universität Tübingen, Eugenstr. 3, 73230, Kirchheim unter Teck, Deutschland
| | - B Hellmich
- Referenzlabor für Vaskulitis-Immundiagnostik, Vaskulitiszentrum Süd, Klinik für Innere Medizin, Rheumatologie und Immunologie, Kreiskliniken Esslingen gGmbH, Klinik Kirchheim, Akademisches Lehrkrankenhaus der Universität Tübingen, Eugenstr. 3, 73230, Kirchheim unter Teck, Deutschland
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Kim BR, Seo Y, Yoon JS. A Retrospective Analysis of Granulomatosis with Polyangiitis with Ocular Manifestations. JOURNAL OF THE KOREAN OPHTHALMOLOGICAL SOCIETY 2017. [DOI: 10.3341/jkos.2017.58.10.1115] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- Bo-ram Kim
- The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea
| | - Yuri Seo
- The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Sook Yoon
- The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea
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37
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Rodrigues AV, Puri CP, Bhanushali PB, Shukla KK, Roychoudhury S, Badgujar SB. Development of an indirect immunofluorescence based assay for diagnosis of ulcerative colitis in Indian population. Immunol Lett 2016; 181:20-25. [PMID: 27845152 DOI: 10.1016/j.imlet.2016.11.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 11/10/2016] [Indexed: 01/08/2023]
Abstract
The prevalence of Ulcerative Colitis (UC), once thought to be negligible, has increases exponentially in the Indian population. The development of novel, cost effective and time efficient Indirect Immunofluorescence (IIF) based assay for detection of anti-neutrophil cytoplasmic antibodies (ANCA) and diagnosis of UC in the Indian population is discussed. A novel IIF based assay was developed using intact nuclei from human neutrophils to detect atypical p-ANCA in patients suffering from UC. Sera from 45 patients diagnosed with UC, 45 healthy controls and one related disease control were tested using a novel UC-ANCA assay and validated by commercially available ANCA IIF assay. Prevalence of ANCA amongst UC patients in the Indian population was determined. Atypical p-ANCA was detected in 86.6% of the patients using the UC-ANCA assay as compared to 71.1% using the commercial ANCA assay. The validation of UC-ANCA assay with a commercially available ANCA IIF assay resulted in higher sensitivity. The UC-ANCA assay proved to be not only enhanced in terms of performance but also comparatively economical and rapid. The novel UC-ANCA assay may prove to be very useful in identification and differentiation of UC patients from typical ANCA positive subjects suffering from other autoimmune diseases at one tenth the cost of clinically available ANCA IIF tests which will immensely benefit the cost constrained diagnostic field of developing countries.
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Affiliation(s)
- Allan V Rodrigues
- Laboratory of Applied Immunology, Research and Development Division, Yashraj Biotechnology Ltd., Navi Mumbai 400705, India; Department of Medical Biotechnology, MGM Institute of Health Sciences, Kamothe, Navi Mumbai 410209, India
| | - Chander P Puri
- Department of Medical Biotechnology, MGM Institute of Health Sciences, Kamothe, Navi Mumbai 410209, India
| | - Paresh B Bhanushali
- Laboratory of Applied Immunology, Research and Development Division, Yashraj Biotechnology Ltd., Navi Mumbai 400705, India; Department of Medical Biotechnology, MGM Institute of Health Sciences, Kamothe, Navi Mumbai 410209, India
| | - Kunal K Shukla
- Laboratory of Applied Immunology, Research and Development Division, Yashraj Biotechnology Ltd., Navi Mumbai 400705, India
| | - Sampurna Roychoudhury
- Laboratory of Applied Immunology, Research and Development Division, Yashraj Biotechnology Ltd., Navi Mumbai 400705, India
| | - Shamkant B Badgujar
- Laboratory of Applied Immunology, Research and Development Division, Yashraj Biotechnology Ltd., Navi Mumbai 400705, India; Department of Biochemistry, National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai 400012 India.
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Sowa M, Trezzi B, Hiemann R, Schierack P, Grossmann K, Scholz J, Somma V, Sinico RA, Roggenbuck D, Radice A. Simultaneous comprehensive multiplex autoantibody analysis for rapidly progressive glomerulonephritis. Medicine (Baltimore) 2016; 95:e5225. [PMID: 27858870 PMCID: PMC5591118 DOI: 10.1097/md.0000000000005225] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Rapidly progressive glomerulonephritis (RPGN) is mainly caused by anti-glomerular basement membrane (GBM) antibody-mediated glomerulonephritis, immune-complex or anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides and leads to rapid loss of renal function. Detection of ANCA and autoantibodies (autoAbs) to GBM and dsDNA enables early diagnosis and appropriate treatment of RPGN aiding in preventing end-stage renal disease.Determination of ANCA on neutrophils (ANCA) as well as autoAbs to myeloperoxidase (MPO-ANCA), proteinase 3 (PR3-ANCA), GBM, and dsDNA was performed by the novel multiplex CytoBead technology combining cell- and microbead-based autoAb analyses by automated indirect immunofluorescence (IIF). Forty patients with granulomatosis with polyangiitis (GPA), 48 with microscopic polyangiitis (MPA), 2 with eosinophilic GPA, 42 with systemic lupus erythematosus (SLE), 43 with Goodpasture syndrome (GPS), 57 with infectious diseases (INF), and 55 healthy subjects (HS) were analyzed and findings compared with classical single testing.The CytoBead assay revealed for GPA, MPA, GPS, and SLE the following diagnostic sensitivities and for HS and INF the corresponding specificities: PR3-ANCA, 85.0% and 100.0%; MPO-ANCA, 77.1% and 99.1%; anti-GBM autoAb, 88.4% and 96.4%; anti-dsDNA autoAb, 83.3% and 97.3%; ANCA, 91.1% and 99.1%, respectively. Agreement with classical enzyme-linked immunosorbent assay and IIF was very good for anti-GBM autoAb, MPO-ANCA, PR3-ANCA, and ANCA, respectively. Anti-dsDNA autoAb comparative analysis demonstrated fair agreement only and a significant difference (P = 0.0001).The CytoBead technology provides a unique multiplex reaction environment for simultaneous RPGN-specific autoAb testing. CytoBead RPGN assay is a promising alternative to time-consuming single parameter analysis and, thus, is well suited for emergency situations.
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Affiliation(s)
- Mandy Sowa
- Research and Development Department, GA Generic Assays GmbH, Dahlewitz/Berlin, Germany
- Correspondence: Mandy Sowa, Medipan GmbH, Ludwig-Erhard-Ring 3, 15827 Dahlewitz, Germany (e-mail: )
| | - Barbara Trezzi
- Clinical Immunology, San Carlo Borromeo Hospital, Milan, Italy
| | - Rico Hiemann
- Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg
| | - Peter Schierack
- Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg
| | - Kai Grossmann
- Research and Development Department, GA Generic Assays GmbH, Dahlewitz/Berlin, Germany
| | - Juliane Scholz
- Research and Development Department, GA Generic Assays GmbH, Dahlewitz/Berlin, Germany
| | - Valentina Somma
- Research and Development Department, Medipan GmbH, Dahlewitz/Berlin, Germany
| | - Renato Alberto Sinico
- Department of Medicine and Surgery, Università degli Studi di Milano - Bicocca (School of Medicine and Surgery), via Cadore, 48 - 20900 Monza (MB)
| | - Dirk Roggenbuck
- Research and Development Department, GA Generic Assays GmbH, Dahlewitz/Berlin, Germany
- Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg
| | - Antonella Radice
- Microbiology Institute, San Carlo Borromeo Hospital, Milan, Italy
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Yates M, Watts RA, Bajema IM, Cid MC, Crestani B, Hauser T, Hellmich B, Holle JU, Laudien M, Little MA, Luqmani RA, Mahr A, Merkel PA, Mills J, Mooney J, Segelmark M, Tesar V, Westman K, Vaglio A, Yalçındağ N, Jayne DR, Mukhtyar C. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 2016; 75:1583-94. [PMID: 27338776 DOI: 10.1136/annrheumdis-2016-209133] [Citation(s) in RCA: 785] [Impact Index Per Article: 87.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Accepted: 05/27/2016] [Indexed: 12/13/2022]
Abstract
In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations.
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Affiliation(s)
- M Yates
- Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK Norwich Medical School, University of East Anglia, Norwich, UK
| | - R A Watts
- Norwich Medical School, University of East Anglia, Norwich, UK Department of Rheumatology, Ipswich Hospital NHS Trust, Ipswich, Suffolk, UK
| | - I M Bajema
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
| | - M C Cid
- Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - B Crestani
- Assistance Publique-Hôpitaux de Paris, Department of Pulmonology, Bichat-Claude Bernard University Hospital, Paris, France
| | - T Hauser
- Immunologie-Zentrum Zürich, Zürich, Switzerland
| | - B Hellmich
- Vaskulits-Zentrum Süd, Klinik für Innere Medizin, Rheumatologie und Immunologie, Kreiskliniken Esslingen, Kirchheim-Teck, Germany
| | - J U Holle
- Rheumazentrum Schleswig-Holstein Mitte, Neumünster, Germany
| | - M Laudien
- Department of Otorhinolaryngology, Head and Neck Surgery, University of Kiel, Kiel, Germany
| | - M A Little
- Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland
| | - R A Luqmani
- Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, United Kingdom
| | - A Mahr
- Department of Internal Medicine, Hôpital Saint-Louis, Université Paris 7 René Diderot, Paris, France
| | - P A Merkel
- Division of Rheumatology and the Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - J Mills
- Vasculitis UK, West Bank House, Winster, Matlock, UK
| | - J Mooney
- Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK
| | - M Segelmark
- Department of Medical and Health Sciences, Linköping University, Linköping, Sweden Department of Nephrology, Linköping University, Linköping, Sweden
| | - V Tesar
- Department of Nephrology, 1st School of Medicine, Charles University, Prague, Czech Republic
| | - K Westman
- Department of Nephrology, Lund University, Skåne University Hospital, Lund and Malmö, Sweden
| | - A Vaglio
- Nephrology Unit, University Hospital of Parma, Parma, Italy
| | - N Yalçındağ
- Department of Ophthalmology, School of Medicine, Ankara University, Ankara, Turkey
| | - D R Jayne
- Lupus and Vasculitis Unit, Addenbrooke's Hospital, Cambridge, UK
| | - C Mukhtyar
- Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK
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Mitra S, Minz RW. Autoantibodies in Autoimmune Liver Diseases-Methods of Detection and Interpretation: An Update for the Reporting Pathologist. Int J Surg Pathol 2016; 24:576-85. [PMID: 27388199 DOI: 10.1177/1066896916657643] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Autoimmune liver disease (AILD) is a type of chronic liver disease with autoimmune etiology. The diagnosis of the disease is multipronged and detection of autoantibodies in AILDs is an important diagnostic tool and it also helps in the classification of the disease. There are multiple autoantibodies that are detected in AILDs but none is diagnostic. Moreover, these autoantibodies are detected in many other pathological and nonpathological conditions. So the significance of seropositivity for these autoantibodies should be known by both the pathologists as well as the clinicians. In addition, there is prognostic significance associated with some of the antibodies and they also sometimes help in the disease monitoring. The whole array of antibodies detected in AILDs is discussed in detail in this review along with their clinical significance and interpretation.
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Affiliation(s)
- Suvradeep Mitra
- PGIMER (Post-Graduate Institute of Medical Education and Research), Chandigarh, India
| | - Ranjana Walker Minz
- PGIMER (Post-Graduate Institute of Medical Education and Research), Chandigarh, India
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Csernok E, Damoiseaux J, Rasmussen N, Hellmich B, van Paassen P, Vermeersch P, Blockmans D, Cohen Tervaert JW, Bossuyt X. Evaluation of automated multi-parametric indirect immunofluorescence assays to detect anti-neutrophil cytoplasmic antibodies (ANCA) in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Autoimmun Rev 2016; 15:736-41. [DOI: 10.1016/j.autrev.2016.03.010] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 03/03/2016] [Indexed: 01/03/2023]
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Jarrot PA, Kaplanski G. Pathogenesis of ANCA-associated vasculitis: An update. Autoimmun Rev 2016; 15:704-13. [DOI: 10.1016/j.autrev.2016.03.007] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Accepted: 03/01/2016] [Indexed: 01/17/2023]
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Chen D, Xie N, Lin Y, Yang Z, Liu W, Wu S, Chen J, Pan X, Yang S, Cai Y. Diagnostic value of antineutrophil cytoplasmic antibodies in children with bronchiolitis obliterans. J Thorac Dis 2016; 8:1306-1315. [PMID: 27293851 PMCID: PMC4886013 DOI: 10.21037/jtd.2016.05.04] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 05/09/2016] [Indexed: 08/15/2023]
Abstract
BACKGROUND Diagnosis of childhood bronchiolitis obliterans (BO) is difficult owing to non-specific clinical presentations and limited investigational options. There is a lack in established serum biomarkers for BO. While the diagnostic value of antineutrophil cytoplasmic antibodies (ANCAs) has been discussed, little is known about this in BO. We aimed to investigate the serological profiles of ANCAs against myeloperoxidase (MPO-ANCA) and proteinase-3 (PR3-ANCA) in BO and acute pneumonia. METHODS In this study, 42 BO children (BO group) and 43 with mild acute pneumonia (pneumonia group) were included, based on rigorous diagnostic criteria and additional constraints for minimizing selection bias. Serum MPO-ANCA and PR3-ANCA levels were measured on the first (baseline) and the last day of hospitalization (on discharge) by enzyme linked immunosorbent assay. RESULTS Although the BO children had a longer hospital stay, the overall rate of positivity (≥180 AAU/mL) and median serum level of MPO-ANCA were higher in the BO group compared with the pneumonia group, either at baseline (69.1% vs. 9.3%, 292.00 vs. 104.75 AAU/mL, both P<0.001) or on discharge (61.9% vs. 9.3%, 310.50 vs. 95.42 AAU/mL). Similar was found for PR3-ANCA (38.1% vs. 4.7%, 106.66 vs. 54.56 AAU/mL at baseline; 35.7% vs. 2.3%, 97.98 vs. 57.23 AAU/mL on discharge, both P<0.001). There were a higher rate of dual-positivity and a lower rate of dual-negativity to both ANCAs in the BO group than those in the pneumonia group (all P<0.001). CONCLUSIONS Detection of MPO- and PR3-ANCA can help diagnosis of childhood BO.
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Avery TY, Bons J, van Paassen P, Damoiseaux J. Diagnostic ANCA algorithms in daily clinical practice: evidence, experience, and effectiveness. Lupus 2016; 25:917-24. [DOI: 10.1177/0961203316640921] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Detection of antineutrophil cytoplasmic antibodies (ANCA) for ANCA-associated vasculitides (AAV) is based on indirect immunofluorescence (IIF) on ethanol-fixed neutrophils and reactivity toward myeloperoxidase (MPO) and proteinase 3 (PR3). According to the international consensus for ANCA testing, presence of ANCA should at least be screened for by IIF and, if positive, followed by antigen-specific immunoassays. Optimally, all samples are analyzed by both IIF and quantitative antigen-specific immunoassays. Since the establishment of this consensus many new technologies have become available and this has challenged the positioning of IIF in the testing algorithm for AAV. In the current paper, we summarize the novelties in ANCA diagnostics and discuss the possible implications of these developments for the different ANCA algorithms that are currently applied in routine diagnostic laboratories. Possible consequences of replacing ANCA assays by novel methods are illustrated by our data obtained in daily clinical practice. Eventually, it is questioned if there is a need to change the consensus, and if so, whether IIF can be discarded completely, or be used as a confirmation assay instead of a screening assay. Both alternative options require that ANCA requests for AAV can be separated from ANCA requests for gastrointestinal autoimmune diseases.
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Affiliation(s)
- T Y Avery
- Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands
| | - J Bons
- Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands
| | - P van Paassen
- Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - J Damoiseaux
- Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands
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Sung IY, Kim YM, Cho YC, Son JH. Role of gingival manifestation in diagnosis of granulomatosis with polyangiitis (Wegener's granulomatosis). J Periodontal Implant Sci 2015; 45:247-51. [PMID: 26734495 PMCID: PMC4698952 DOI: 10.5051/jpis.2015.45.6.247] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Accepted: 11/27/2015] [Indexed: 11/22/2022] Open
Abstract
Purpose This report describes a case of granulomatosis with polyangiitis (GPA) in which the gingival manifestation was crucial in both making an early diagnosis and possibly in deciding the approach to treatment. Methods A 57-year-old sailor presented to the Department of Dentistry at Ulsan University Hospital complaining of gingival swelling since approximately 2 months. He had orofacial granulomatous lesions and the specific gingival manifestation of strawberry gingivitis. Results The diagnosis of GPA was made on the basis of clinical symptoms and signs, and confirmed by the presence of the anti-neutrophil cytoplasmic antibody and a positive biopsy. The patient was admitted to the hospital and subsequently placed on a disease-modifying therapy regimen that included methotrexate and prednisone. Conclusions Identification of the gingival manifestation of the disease permitted an early diagnosis and prompt therapy in a disease in which time is a crucial factor. Because of its rapid progression and potentially fatal outcome, an early diagnosis of GPA is important. Therefore, dentists should be aware of the oral signs and symptoms of such systemic diseases.
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Affiliation(s)
- Iel-Yong Sung
- Department of Dentistry, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Young-Min Kim
- Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Yeong-Cheol Cho
- Department of Dentistry, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Jang-Ho Son
- Department of Dentistry, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
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Balavoine AS, Glinoer D, Dubucquoi S, Wémeau JL. Antineutrophil Cytoplasmic Antibody-Positive Small-Vessel Vasculitis Associated with Antithyroid Drug Therapy: How Significant Is the Clinical Problem? Thyroid 2015; 25:1273-81. [PMID: 26414658 DOI: 10.1089/thy.2014.0603] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND The aim of this review was to delineate the characteristics of antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis associated with antithyroid drugs (ATD). A PubMed search was made for English language articles using the search terms antithyroid drugs AND ANCA OR ANCA-associated vasculitis. SUMMARY The literature includes approximately 260 case reports of ANCA-associated small-vessel vasculitis related to ATD, with 75% of these associated with thiouracil derivatives (propylthiouracil [PTU]) and 25% with methyl-mercapto-imidazole derivatives (MMI/TMZ). The prevalence of ANCA-positive cases caused by ATD varied between 4% and 64% with PTU (median 30%), and 0% and 16% with MMI/TMZ (median 6%). Young age and the duration of ATD therapy were the main factors contributing to the emergence of ANCA positivity. Before ATD therapy initiation, the prevalence of ANCA-positive patients was 0-13%. During ATD administration, 20% of patients were found to be positive for ANCA. Only 15% of ANCA-positive patients treated with ATD exhibited clinical evidence of vasculitis, corresponding to 3% of all patients who received ATD. Clinical manifestations of ANCA-associated vasculitis related to ATD were extremely heterogeneous. When vasculitis occurred, ATD withdrawal was usually followed by rapid clinical improvement and a favorable prognosis. CONCLUSIONS ANCA screening is not systematically recommended for individuals on ATD therapy, particularly given the decreasing use of PTU in favor of TMZ/MMI. Particular attention should be given to the pediatric population with Graves' disease who receive ATD, as well as patients treated with thiouracil derivatives and those on long-term ATD therapy.
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Affiliation(s)
| | - Daniel Glinoer
- 2 Department of Internal Medicine, Division of Endocrinology, University Hospital Saint Pierre , Brussels, Belgium
| | | | - Jean-Louis Wémeau
- 1 Service of Endocrinology and Metabolic Diseases, CHRU de Lille , Lille, France
- 3 Institut d'Immunologie, CHRU de Lille , Lille, France
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Abstract
Autoantibodies are the serological hallmark of autoimmune disease. Though their pathogenic role is debatable, they play an important role in the management of a patient with rheumatic disease. However, due to their presence in the general population as well as in multiple autoimmune diseases, the presence of an autoantibody alone does not make a diagnosis; the result has to be interpreted along with clinical findings. Similarly, the absence of autoantibody does not exclude a disease. The common autoantibodies used in clinical practice include rheumatoid factor, anti-CCP antibodies, antinuclear antibodies (ANAs), anti-neutrophil cytoplasmic antibodies (ANCA) and anti-phospholipid antibodies. Once an autoantibody to a broad antigen is detected in a patient, sub-specificity analysis can improve the utility of the antibody. Autoantibodies are detected in the serum using different assays and results of which can vary; thus, it is important for a clinician to know the method used, its sensitivity and specificity to help in the proper interpretation of the laboratory results. This review will address these issues.
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Affiliation(s)
- Amita Aggarwal
- Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
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Microscopic polyangiitis: Advances in diagnostic and therapeutic approaches. Autoimmun Rev 2015; 14:837-44. [PMID: 25992801 DOI: 10.1016/j.autrev.2015.05.005] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2015] [Accepted: 05/12/2015] [Indexed: 11/24/2022]
Abstract
Microscopic polyangiitis (MPA) is an idiopathic autoimmune disease characterized by systemic vasculitis. The disease predominantly affects small-calibre blood vessels and is associated with the presence of antineutrophil cytoplasmic autoantibodies (ANCA). Microscopic polyangiitis was considered to be a disease entity by Savage et al. in 1985. Microscopic polyangiitis has a reported low incidence and a slight male predominance. The aetiology of MPA remains unknown. There is, however, increased evidence that MPA is an autoimmune disease in which ANCAs, particularly those reacting with MPO, are pathogenic. MPA belongs to the systemic vasculitides, indicating that multiple organs can be affected. The major organs involved in MPA are the kidneys and the lungs. As expected for an illness that affects multiple organ systems, patients with MPA can present with a myriad of different symptoms. Ear, nose and throat (ENT) manifestations are not considered to be clinical symptoms of MPA, but in the majority of populations described, ENT involvement was found in surprisingly high percentages. MPA is part of the ANCA-associated vasculitides, which are characterized by necrotizing vasculitis of small vessels. Diagnosis is mainly established by clinical manifestations, computed tomography (TC), ANCA antibody detection and renal and pulmonary biopsy. The introduction of aggressive immunosuppressive treatment has substantially improved the prognosis. The standardized therapeutic regimen is based on cyclophosphamide and corticosteroids. Using this regimen, remission can be achieved in most of the patients. Rituximab may represent an important alternative to cyclophosphamide for patients who may not respond adequately to antimetabolite therapies.
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Rao DA, Wei K, Merola JF, O'Brien WR, Takvorian SU, Dellaripa PF, Schur PH. Myeloperoxidase-antineutrophil Cytoplasmic Antibodies (MPO-ANCA) and Proteinase 3-ANCA without Immunofluorescent ANCA Found by Routine Clinical Testing. J Rheumatol 2015; 42:847-52. [PMID: 25834211 DOI: 10.3899/jrheum.140941] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/23/2015] [Indexed: 11/22/2022]
Abstract
OBJECTIVE Concurrent testing for serum antineutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IF) and by antiproteinase 3 (PR3)/antimyeloperoxidase (MPO) antibody assays may identify patients with PR3-ANCA or MPO-ANCA despite a negative IF (IF-negative MPO/PR3-positive); however, the significance of this result is not clear. We sought to determine whether IF-negative, MPO/PR3-positive results identified any cases of clinically meaningful systemic vasculitis at our institution. METHODS We conducted a retrospective chart review of all IF-negative, MPO/PR3-positive patients identified at our institution over a 2-year period. RESULTS Of the 2345 samples tested over 2 years, 1998 were IF-negative. Among these IF-negative samples, 49 samples (2.5%) derived from 38 patients tested positive for MPO-ANCA or PR3-ANCA. Only 1 IF-negative, MPO/PR3-positive patient was subsequently diagnosed with ANCA-associated vasculitis (AAV). Eleven IF-negative, MPO/PR3-positive patients (29%) had been previously diagnosed and treated for AAV, all with positive IF and antibody tests prior to treatment. Four patients had evidence of cutaneous vasculitis not attributed to AAV, while several of the remaining IF-negative, MPO/PR3-positive patients had other immunologic disorders, including systemic lupus erythematosus (5 patients) and inflammatory bowel disease (3 patients). CONCLUSION In this real-life cohort assayed simultaneously by IF and multiplexed bead assays, the detection of MPO-ANCA or PR3-ANCA without a positive IF rarely led to a new diagnosis of systemic vasculitis, and was more likely to occur in the context of a non-vasculitic inflammatory condition. Our results suggest that concurrent IF and MPO/PR3 testing may be of limited use in preventing a missed diagnosis of new-onset AAV.
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Affiliation(s)
- Deepak A Rao
- From the Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA.D.A. Rao, MD, PhD, Fellow in Rheumatology; K. Wei, MD, PhD, Fellow in Rheumatology; W.R. O'Brien, Fellow in Rheumatology; S.U. Takvorian, MD, Resident in Internal Medicine; P.F. Dellaripa, MD, Assistant Professor of Medicine; P.H. Schur, MD, Professor of Medicine, Brigham and Women's Hospital; J.F. Merola, MD, Instructor, Harvard Medical School
| | - Kevin Wei
- From the Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA.D.A. Rao, MD, PhD, Fellow in Rheumatology; K. Wei, MD, PhD, Fellow in Rheumatology; W.R. O'Brien, Fellow in Rheumatology; S.U. Takvorian, MD, Resident in Internal Medicine; P.F. Dellaripa, MD, Assistant Professor of Medicine; P.H. Schur, MD, Professor of Medicine, Brigham and Women's Hospital; J.F. Merola, MD, Instructor, Harvard Medical School
| | - Joseph F Merola
- From the Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA.D.A. Rao, MD, PhD, Fellow in Rheumatology; K. Wei, MD, PhD, Fellow in Rheumatology; W.R. O'Brien, Fellow in Rheumatology; S.U. Takvorian, MD, Resident in Internal Medicine; P.F. Dellaripa, MD, Assistant Professor of Medicine; P.H. Schur, MD, Professor of Medicine, Brigham and Women's Hospital; J.F. Merola, MD, Instructor, Harvard Medical School
| | - William R O'Brien
- From the Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA.D.A. Rao, MD, PhD, Fellow in Rheumatology; K. Wei, MD, PhD, Fellow in Rheumatology; W.R. O'Brien, Fellow in Rheumatology; S.U. Takvorian, MD, Resident in Internal Medicine; P.F. Dellaripa, MD, Assistant Professor of Medicine; P.H. Schur, MD, Professor of Medicine, Brigham and Women's Hospital; J.F. Merola, MD, Instructor, Harvard Medical School
| | - Samuel U Takvorian
- From the Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA.D.A. Rao, MD, PhD, Fellow in Rheumatology; K. Wei, MD, PhD, Fellow in Rheumatology; W.R. O'Brien, Fellow in Rheumatology; S.U. Takvorian, MD, Resident in Internal Medicine; P.F. Dellaripa, MD, Assistant Professor of Medicine; P.H. Schur, MD, Professor of Medicine, Brigham and Women's Hospital; J.F. Merola, MD, Instructor, Harvard Medical School
| | - Paul F Dellaripa
- From the Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA.D.A. Rao, MD, PhD, Fellow in Rheumatology; K. Wei, MD, PhD, Fellow in Rheumatology; W.R. O'Brien, Fellow in Rheumatology; S.U. Takvorian, MD, Resident in Internal Medicine; P.F. Dellaripa, MD, Assistant Professor of Medicine; P.H. Schur, MD, Professor of Medicine, Brigham and Women's Hospital; J.F. Merola, MD, Instructor, Harvard Medical School.
| | - Peter H Schur
- From the Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA.D.A. Rao, MD, PhD, Fellow in Rheumatology; K. Wei, MD, PhD, Fellow in Rheumatology; W.R. O'Brien, Fellow in Rheumatology; S.U. Takvorian, MD, Resident in Internal Medicine; P.F. Dellaripa, MD, Assistant Professor of Medicine; P.H. Schur, MD, Professor of Medicine, Brigham and Women's Hospital; J.F. Merola, MD, Instructor, Harvard Medical School.
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Sayegh J, Poli C, Chevailler A, Subra JF, Beloncle F, Deguigne PA, Beauvillain C, Augusto JF. Emergency testing for antineutrophil cytoplasmic antibodies combined with a dialog-based policy between clinician and biologist: effectiveness for the diagnosis of ANCA-associated vasculitis. Intern Emerg Med 2015; 10:315-9. [PMID: 25343851 DOI: 10.1007/s11739-014-1141-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Accepted: 10/15/2014] [Indexed: 10/24/2022]
Abstract
A prompt immunosuppressive treatment initiation is crucial in ANCA-associated vasculitis (AAV) to minimize organ injury. The aim of the present work was to analyze the accuracy of emergency ANCA screening to identify rapidly patients with AAV. In our Institution, emergency ANCA screening is based on a telephone call between a Clinician and a Biologist. Indirect immunofluorescence (IIF) for ANCA detection was performed using a commercial kit (Euroimmun(®) Granulocyte Mosaic 12). Positive serums for c- or p-ANCA at IIF are subsequently screened for antigenic specificity (MPO or PR3) by an immunodot technique (immunodot, D-Tek(®).) Positive samples with atypical c- or p-ANCA pattern at IIF are subsequently screened for antigenic specificity by ELISA. Data were retrieved from patients' medical records and confronted to emergency ANCA screening results. Between 2005 and 2012, 114 patients were screened. IIF was positive in 27.2% of patients, but c-/p-ANCA anti-MPO/-PR3 was detected in 13.2% of patients. The sensibility and specificity of IIF combined with immunodot for newly diagnosed AAV were 83.3 and 100%, respectively. Ten patients were newly diagnosed with AAV. In these patients, a specific AAV treatment was initiated less than 24 h following ANCA screening. Emergency ANCA screening based on a clinical gating policy was relevant to identify patients with AAV diagnosis, and was associated with a rapid treatment initiation.
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