|
1
|
Ghozzi M, Mankai A, Zneidi I, Manoubi W, Melayah S, Mechi F, Trabelsi A, Ghedira I. Serological markers of rheumatoid arthritis in patients with primary biliary cholangitis and the vice versa: A Tunisian study. Immunobiology 2023; 228:152398. [PMID: 37269587 DOI: 10.1016/j.imbio.2023.152398] [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: 02/09/2023] [Revised: 04/14/2023] [Accepted: 05/24/2023] [Indexed: 06/05/2023]
Abstract
BACKGROUND Primary biliary cholangitis (PBC) is an autoimmune disease of the liver characterized by destructive lymphocytic cholangitis and anti-mitochondrial antibodies (AMA). Anti-gp210 and anti-Sp100, are used for the diagnosis of PBC in AMA-negative PBC patients. Patients with PBC have a propensity to have an extrahepatic manifestation which is especially autoimmune. OBJECTIVE We aimed to determine the frequency of serological markers of rheumatoid arthritis (RA) (CCP-Ab or RF) in PBC patients and to do the vice versa. METHODS Our PBC study included 70 patients with PBC and 80 healthy blood donors (HBD) and our RA study included 75 patients with RA and 75 HBD. Anti-cyclic citrullinated peptide antibodies (CCP-Ab) and rheumatoid factor (RF) were performed by indirect ELISA. AMA, anti-Sp100 and anti-gp210 were determined by indirect immunofluorescence. RESULTS RA autoantibodies (CCP-Ab or RF) were more frequent in PBC patients than in HBD (65.7% vs. 8.7% p 〈10-6). CCP-Ab were significantly more frequent in patients than in controls (15.7% vs. 2.5%; p = 0.004). Nine patients had both CCP-Ab and RF vs. none of controls (12.8% vs. 0%; p = 0.001). RF were detected in 45 patients with PBC and in 5 HBD (64.3% vs. 6.2%; p 〈10-6). In PBC patients, RF were more frequent than CCP-Ab (64.3% vs. 15.7%; p 〈10-6). RF-IgG were present in 18.5% of patients; RF-immunoglobulin (Ig) A in 34.3% and RF-IgM in 54.3%. These frequencies were significantly higher than those found in control group (1.2% for RF-IgG (p 〈10-3); 0% for RF-IgA (p 〈10-6); and 6.2% for RF-IgM (p 〈10-6)). In our PBC patients, RF-IgA were more frequent than RF-IgG (34.3% vs. 18.5%; p = 0.03) and than CCP-Ab (34.3% vs. 15.7%; p = 0.01). Six patients had only RF-IgA versus none of the control group (8.6% vs. 0%; p = 0.01). AMA, anti-Sp100 and anti-gp 210 were absent in all RA patients. CONCLUSIONS Serological markers of RA were more frequent in PBC patients than in HBD and the vice versa was not true.
Collapse
Affiliation(s)
- Mariam Ghozzi
- Laboratory of Immunology, Farhat Hached University Hospital, Sousse, Tunisia; Faculty of Pharmacy, Department of Immunology, University of Monastir, Monastir, Tunisia; Research Laboratory for "Epidemiology and Immunogenetics of Viral Infections" (LR14SP02), Sahloul University Hospital, University of Sousse, Sousse, Tunisia.
| | - Amani Mankai
- High School of Sciences and Techniques of Health, Tunis El Manar University, Tunis, Tunisia; Research Unit "Obesity: Etiopathology and Treatment, UR18ES01", National Institute of Nutrition and Food Technology, Tunis, Tunisia
| | - Inssaf Zneidi
- Faculty of Pharmacy, Department of Immunology, University of Monastir, Monastir, Tunisia
| | - Wiem Manoubi
- Erasmus University Medical Centre, Department of Neuroscience, Rotterdam, Netherlands
| | - Sarra Melayah
- Laboratory of Immunology, Farhat Hached University Hospital, Sousse, Tunisia; Faculty of Pharmacy, Department of Immunology, University of Monastir, Monastir, Tunisia; LR12SP11, Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia
| | - Fatma Mechi
- Laboratory of Immunology, Farhat Hached University Hospital, Sousse, Tunisia; Faculty of Pharmacy, Department of Immunology, University of Monastir, Monastir, Tunisia
| | - Abdelhalim Trabelsi
- Research Laboratory for "Epidemiology and Immunogenetics of Viral Infections" (LR14SP02), Sahloul University Hospital, University of Sousse, Sousse, Tunisia; Laboratory of Microbiology and Virology, Sahloul University Hospital, Sousse, Tunisia
| | - Ibtissem Ghedira
- Laboratory of Immunology, Farhat Hached University Hospital, Sousse, Tunisia; Faculty of Pharmacy, Department of Immunology, University of Monastir, Monastir, Tunisia
| |
Collapse
|
|
2
|
Badiee F, Fatemi A, Zahedpasha R, Gharib MH, Jokar M, Livani S, Aghaie M, Abdolahi N. Hands and feet radiologic involvements in systemic sclerosis. BMC Rheumatol 2023; 7:9. [PMID: 37208734 DOI: 10.1186/s41927-023-00336-9] [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: 12/10/2021] [Accepted: 05/04/2023] [Indexed: 05/21/2023] Open
Abstract
AIM Systemic sclerosis (SSc) is a rare autoimmune disorder characterized by vascular and fibrosing involvement of the skin and internal organs. In this study, we determined the prevalence and characteristics of radiological hands and feet involvements in Iranian SSc patients to identify the associations between clinical features and radiologic findings. METHODS 43 SSc patients (41 women and 2 men), with a median age of 44.8 years (ranges 26-70 years) and a mean disease duration of 11.8 years (ranges 2-28 years) were studied in this cross-sectional study. RESULTS 42 patients had radiological changes both in their hands and feet. Only one patient had alteration just in hand. The most frequent changes that we found in hand were Juxta-articular Osteoporosis (93%), Acro-osteolysis (58.2%), and Joint Space Narrowing (55.8%). The prevalence of joint space narrowing or acro-osteolysis was higher in subjects with active skin involvement [modified Rodnan skin score (mRSS) > 14] [16/21 vs. 4/16 for patients with inactive skin involvement (mRSS < 14); p = 0.002]. The most frequent changes that we found in the foot were Juxta-articular Osteoporosis (93%), Acro-osteolysis (46.5%), Joint Space Narrowing (58.1%), and subluxation (44.2%). The presence of anti-ccp antibody was detected in 4 (9.3%), while positive rheumatoid factor was found in 13 (30.2%) of SSc patients. CONCLUSION This study corroborates that arthropathy is common in SSc patients. The introduction of the specific radiological involvements of SSc needs to be confirmed by further studies, in order to define the appropriate prognosis and treatment of patients.
Collapse
Affiliation(s)
- Fatemeh Badiee
- Golestan Rheumatology Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Alireza Fatemi
- Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran
| | - Reza Zahedpasha
- Golestan Rheumatology Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Mohammad Hadi Gharib
- Department of Radiology, School of Medicine, 5Th Azar Hospital, Gorgan, Golestan, Iran
- Golestan University of Medical Sciences, Gorgan, Golestan, Iran, Islamic Republic of
| | - Mohammadhassan Jokar
- Golestan Rheumatology Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Somayeh Livani
- Golestan University of Medical Sciences, Gorgan, Golestan, Iran, Islamic Republic of
- Clinical Research Development Unit (CRDU), Sayad Shirazi Hospital, Gorgan, Iran, Islamic Republic of
| | - Mehrdad Aghaie
- Golestan Rheumatology Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Nafiseh Abdolahi
- Golestan Rheumatology Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
| |
Collapse
|
|
3
|
Mortazavi N, Abdolahi N, Saeidi M, Ali Vakili M, Mohebrad P. Salivary anti-cyclic citrullinated peptide as a screening tool for rheumatoid arthritis. Arch Rheumatol 2023; 38:95-100. [DOI: 10.46497/archrheumatol.2023.9032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 03/11/2022] [Indexed: 03/18/2023] Open
Abstract
Objectives: This study aims to evaluate the sensitivity and specificity of salivary anti-cyclic citrullinated peptide 3 (anti-CCP3) for the early diagnosis of rheumatoid arthritis.
Patients and methods: Between June 2017 and April 2019, a total of 63 patients with rheumatoid arthritis (10 males, 53 females; mean age: 50.4±9.5 years; range, 27 to 74 years) and 49 healthy controls (8 males, 41 females; mean age: 49.3±9.3 years; range 27 to 67 years) were included. Salivary samples were collected by passive drooling. Anti-cyclic citrullinated peptide analyses of salivary and serum samples were performed.
Results: The mean polyclonal immunoglobulin (Ig)G-IgA anti-CCP3 salivary levels were significantly different in patients (149.2±134.2) compared to healthy controls (28.5±23.9). The mean polyclonal IgG-IgA anti-CCP3 serum levels were measured as 254.0±169.5 in patients and 3.8±3.6 in healthy individuals. The diagnostic accuracy analysis of salivary IgG-IgA anti-CCP3 results in an area under the curve (AUC) of 0.818, as well as 91.84% specificity and 61.90% sensitivity.
Conclusion: Salivary anti-CCP3 may be considered as an additional screening test for rheumatoid arthritis.
Collapse
|
|
4
|
Ha JW, Hong YJ, Cha HJ, Moon JD, Pyo JY, Lee SW, Park YB, Park CH, Song JJ. A retrospective analysis of the relationship between anti-cyclic citrullinated peptide antibody and interstitial lung disease in systemic sclerosis. Sci Rep 2022; 12:19253. [PMID: 36357514 PMCID: PMC9649731 DOI: 10.1038/s41598-022-23180-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 10/26/2022] [Indexed: 11/12/2022] Open
Abstract
Anti-cyclic citrullinated peptide antibody testing is used to diagnose rheumatoid arthritis and associated with interstitial lung disease in RA. Herein, we investigate the relationship between anti-CCP antibody and ILD in SSc. We performed a retrospective analysis at a tertiary medical center between 2005 and 2019. Patients with SSc, systemic lupus erythematosus, and polymyositis/dermatomyositis (PM/DM) were evaluated for anti-CCP antibody and ILD. Additionally, medical records of SSc patients with ILD were reviewed. SSc patients had the highest anti-CCP antibody positivity rate compared to those with SLE and PM/DM. The incidence of ILD was higher in SSc patients with anti-CCP antibody than in those without. The usual interstitial pneumonia (UIP) incidence was higher in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. The DLCO was lower in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. On multivariable analysis, factors associated with SSc-ILD were anti-CCP antibody or rheumatoid factor (β coefficient, 2.652 [95% CI 1.472 to 4.776]) and anti-Scl70 antibody (β coefficient, 4.011 [95% CI 2.142 to 7.508]). Anti-CCP antibody may be associated with a higher incidence of ILD in SSc. SSc patients with anti-CCP antibody may have more UIP pattern and lower DLCO.Trial Registration Retrospectively registered.
Collapse
Affiliation(s)
- Jang Woo Ha
- grid.15444.300000 0004 0470 5454Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun–gu, Seoul, 03722 South Korea
| | - Yoo Jin Hong
- grid.15444.300000 0004 0470 5454Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun Jin Cha
- grid.15444.300000 0004 0470 5454Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun–gu, Seoul, 03722 South Korea ,grid.15444.300000 0004 0470 5454Synapse Center, Yonsei University College of Medicine, Seoul, Korea
| | - Jeonghun Daniel Moon
- grid.417231.20000 0000 9880 7822Division of Rheumatology, Valley Medical Center, University of Washington Medicine, Renton, WA 98055 USA
| | - Jung Yoon Pyo
- grid.15444.300000 0004 0470 5454Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun–gu, Seoul, 03722 South Korea
| | - Sang-Won Lee
- grid.15444.300000 0004 0470 5454Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun–gu, Seoul, 03722 South Korea
| | - Yong-Beom Park
- grid.15444.300000 0004 0470 5454Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun–gu, Seoul, 03722 South Korea
| | - Chul Hwan Park
- grid.15444.300000 0004 0470 5454Department of Radiology and Research Institute of Radiological Science, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul, 06273 South Korea
| | - Jason Jungsik Song
- grid.15444.300000 0004 0470 5454Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun–gu, Seoul, 03722 South Korea ,grid.15444.300000 0004 0470 5454Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Korea
| |
Collapse
|
|
5
|
Ru Z, Zhang H, Huang X, Lou J, Liao J, Chen Z, Yang X. A new pattern of citrullinated peptides improves the sensitivity for diagnosing rheumatoid arthritis. Clin Biochem 2022; 105-106:87-93. [DOI: 10.1016/j.clinbiochem.2022.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 03/29/2022] [Accepted: 04/04/2022] [Indexed: 11/03/2022]
|
|
6
|
Riccardi A, Martinroche G, Contin-Bordes C, Avouac J, Gobeaux C, Cauvet A, Guerini H, Truchetet ME, Allanore Y. Erosive arthritis autoantibodies in systemic sclerosis. Semin Arthritis Rheum 2021; 52:151947. [PMID: 35000789 DOI: 10.1016/j.semarthrit.2021.11.013] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 11/03/2021] [Accepted: 11/22/2021] [Indexed: 01/23/2023]
Abstract
OBJECTIVE We aimed to evaluate in two large SSc French cohorts the prevalence and associated factors with the autoantibodies linked to erosive arthritis. METHODS 448 SSc patients were recruited from May 2015 to January 2019. Standardized clinical and laboratory variables were collected in accordance with the EUSTAR database. ELISAs for IgM rheumatoid factor (RF), IgG anti-citrullinated proteins (ACPA) and IgG anti-carbamylated proteins antibodies (anti-CarP) were all determined in a central laboratory. The prevalence and clinical associations of the different antibodies were investigated. RESULTS RF positivity was observed in 113 patients (25%) compared to 39 (9%) for ACPA and 63 (14%) for anti-CarP antibodies. Through multivariate regression analysis, both RF and ACPA positivity resulted to be associated with RA overlap disease (OR 5.7, 95% CI 2.3-13.8 and OR 44.1, 95% CI 15.4-126.3, respectively). Additionally, ACPA was found to be significantly related to synovitis/ tenosynovitis (OR 1.7, 95% CI 1.0-2.6). RF positivity was associated to a "vascular subset" (i.e. any major vascular complication) (OR 2.1, 95% CI 1.3-3.4). Moreover, anti-CarP antibodies were associated with a fibrotic subset and with digital ulcers (OR 2.0, 95% CI 1.1-3.6 and OR 1.9, 95% CI 1.1-3.4). CONCLUSION We corroborated that ACPA could be useful in identifying patients with a more prominent joint disease and RA overlap disease. Of the most interest we found that anti-CarP antibodies could be a relevant biomarker related to fibrotic skin and lung disease.
Collapse
Affiliation(s)
- Antonella Riccardi
- Department of Precision Medicine, Rheumatology Unit, University of Campania "Luigi Vanvitelli", Naples, Italy
| | | | - Cécile Contin-Bordes
- Immunology Department, CHU Bordeaux Hospital, Bordeaux, France; ImmunoConcEpt, CNRS, UMR 5164, University of Bordeaux, France
| | - Jérôme Avouac
- Department of Rheumatology, Descartes University, APHP, Cochin Hospital, Paris, France
| | - Camille Gobeaux
- Department of Biochemistry, Université de Paris, Cochin Hospital, Paris, France
| | - Anne Cauvet
- INSERM U1016, Institut Cochin, Université de Paris, France
| | - Henri Guerini
- Radiology B department, Cochin Hospital, Université de Paris, France
| | - Marie-Elise Truchetet
- ImmunoConcEpt, CNRS, UMR 5164, University of Bordeaux, France; Department of Rheumatology, Descartes University, APHP, Cochin Hospital, Paris, France; Department of Biochemistry, Université de Paris, Cochin Hospital, Paris, France; INSERM U1016, Institut Cochin, Université de Paris, France; Radiology B department, Cochin Hospital, Université de Paris, France; Rheumatology Department, CHU Bordeaux Hospital, Bordeaux, France
| | - Yannick Allanore
- Department of Rheumatology, Descartes University, APHP, Cochin Hospital, Paris, France; Department of Biochemistry, Université de Paris, Cochin Hospital, Paris, France; INSERM U1016, Institut Cochin, Université de Paris, France; Radiology B department, Cochin Hospital, Université de Paris, France; Rheumatology Department, CHU Bordeaux Hospital, Bordeaux, France.
| |
Collapse
|
|
7
|
Alghamdi MF, Redwan EM. Advances in the diagnosis of autoimmune diseases based on citrullinated peptides/proteins. Expert Rev Mol Diagn 2021; 21:685-702. [PMID: 34024239 DOI: 10.1080/14737159.2021.1933946] [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] [Indexed: 12/16/2022]
Abstract
Introduction: Autoimmune diseases are still one of the hard obstacles associated with humanity. There are many exogenous and endogenous etiological factors behind autoimmune diseases, which may be combined or dispersed to stimulate the autoimmune responses. Protein citrullination represents one of these factors. Harnessing specific citrullinated proteins/peptides could early predict and/or diagnose some of the autoimmune diseases. Many generations of diagnostic tools based on citrullinated peptides with comparable specificity/sensitivity are available worldwide.Areas covered: In this review, we discuss the deimination reaction behind the citrullination of most known autoantigens targeted, different generations of diagnostic tools based on citrullinated probes with specificity/sensitivity of each as well as newly developed assays. Furthermore, the most advanced molecular analytical tools to detect the citrullinated residues in the biological fluid and their performance are also evaluated, providing new avenues to early detect autoimmune diseases with high accuracy.Expert opinion: With the current specificity/sensitivity tools available for autoimmune disease detection, emphasis must be placed on developing more advance and effective, early, rapid, and simple diagnostic devices for autoimmune disease monitoring (similar to a portable device for sugar test at home). The molecular analytical devices with dual and/or multiplexe functions should be more simplified and invested in clinical laboratories.
Collapse
Affiliation(s)
- Mohammed F Alghamdi
- Biological Sciences Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.,Laboratory Department, University Medical Services Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Elrashdy M Redwan
- Biological Sciences Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.,Therapeutic and Protective Proteins Laboratory, Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City for Scientific Research and Technology Applications, New Borg EL-Arab, Alexandria, Egypt
| |
Collapse
|
|
8
|
Volkov M, van Schie KA, van der Woude D. Autoantibodies and B Cells: The ABC of rheumatoid arthritis pathophysiology. Immunol Rev 2019; 294:148-163. [PMID: 31845355 PMCID: PMC7065213 DOI: 10.1111/imr.12829] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 11/07/2019] [Indexed: 12/16/2022]
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation. In the last few decades, new insights into RA‐specific autoantibodies and B cells have greatly expanded our understanding of the disease. The best‐known autoantibodies in RA—rheumatoid factor (RF) and anti‐citrullinated protein antibodies (ACPA)—are present long before disease onset, and both responses show signs of maturation around the time of the first manifestation of arthritis. A very intriguing characteristic of ACPA is their remarkably high abundance of variable domain glycans. Since these glycans may convey an important selection advantage of citrulline‐reactive B cells, they may be the key to understanding the evolution of the autoimmune response. Recently discovered autoantibodies targeting other posttranslational modifications, such as anti‐carbamylated and anti‐acetylated protein antibodies, appear to be closely related to ACPA, which makes it possible to unite them under the term of anti‐modified protein antibodies (AMPA). Despite the many insights gained about these autoantibodies, it is unclear whether they are pathogenic or play a causal role in disease development. Autoreactive B cells from which the autoantibodies originate have also received attention as perhaps more likely disease culprits. The development of autoreactive B cells in RA largely depends on the interaction with T cells in which HLA “shared epitope” and HLA DERAA may play an important role. Recent technological advances made it possible to identify and characterize citrulline‐reactive B cells and acquire ACPA monoclonal antibodies, which are providing valuable insights and help to understand the nature of the autoimmune response underlying RA. In this review, we summarize what is currently known about the role of autoantibodies and autoreactive B cells in RA and we discuss the most prominent hypotheses aiming to explain the origins and the evolution of autoimmunity in RA.
Collapse
Affiliation(s)
- Mikhail Volkov
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Karin Anna van Schie
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Diane van der Woude
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
| |
Collapse
|
|
9
|
Trier NH, Holm BE, Hansen PR, Slot O, Locht H, Houen G. Specificity of Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis. Antibodies (Basel) 2019; 8:antib8020037. [PMID: 31544843 PMCID: PMC6640722 DOI: 10.3390/antib8020037] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 05/28/2019] [Accepted: 06/06/2019] [Indexed: 11/16/2022] Open
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. The majority of individuals with RA are positive for the disease-specific anti-citrullinated protein antibodies (ACPAs). These antibodies are primarily of cross-reactive nature, hence, the true autoantigen to ACPA remains unidentified. In this study, we analyzed the reactivity of RA sera to several post-translationally modified epitopes, in order to further characterize the specific nature of ACPAs by immunoassays. Substituting citrulline with other amino acids, e.g., D-citrulline, homo-citrulline and methyl-arginine illustrated that ACPAs are utmost specific for citrullinated targets. Collectively, these findings support that ACPAs and citrullinated targets are specific for RA, making citrulline-containing peptide targets the most effective assays for detection of ACPAs.
Collapse
Affiliation(s)
- Nicole H Trier
- Department of Biomarkers and Autoimmunity, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark.
| | - Bettina E Holm
- Department of Clinical Immunology, Rigshospitalet, Ole Maaløes vej 26, 2200 Copenhagen N, Denmark.
| | - Paul R Hansen
- Department of Drug Design and Pharmacology, Universitetsparken 2, 2100 Copenhagen Ø, Denmark.
| | - Ole Slot
- Department of Rheumatology, Rigshospitalet Glostrup, Nordre Ringvej 57, 2600 Glostrup, Denmark.
| | - Henning Locht
- Department of Rheumatology, Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Frederiksberg, Denmark.
| | - Gunnar Houen
- Department of Biomarkers and Autoimmunity, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark.
| |
Collapse
|
|
10
|
Use of a Citrullinated Peptide Panel for Detection of Anti-Citrullinated Protein Antibodies by Enzyme-Linked Immunosorbent Assay. Methods Mol Biol 2019; 1901:243-253. [PMID: 30539584 DOI: 10.1007/978-1-4939-8949-2_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/10/2023]
Abstract
Anti-citrullinated protein antibodies (ACPA)s are a hallmark of rheumatoid arthritis (RA) and are essential for serological diagnosis of RA.ACPAs are not specific for a single citrullinated target; in fact, several citrullinated ACPA target proteins have been described. As a consequence, ACPAs are primarily detected by enzyme-linked immunosorbent assays, where several citrullinated peptides are used as target antigens.This chapter focuses on the detection of ACPAs using a recently developed peptide panel in enzyme-linked immunosorbent assays.
Collapse
|
|
11
|
Comparative study of the diagnostic and prognostic value of antibodies against chimeric citrullinated synthetic peptides and CCP3/CCP3.1 assays. Clin Chem Lab Med 2019; 56:285-293. [PMID: 28850543 DOI: 10.1515/cclm-2017-0264] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Accepted: 07/20/2017] [Indexed: 11/15/2022]
Abstract
BACKGROUND The objective of the study was to compare the diagnostic yield of home-made ELISA tests based on synthetic chimeric fibrin/filaggrin citrullinated peptides (CFFCPs) with CCP3 and CCP3.1 commercial tests to detect anti-citrullinated protein/peptide antibodies (ACPAs) in rheumatoid arthritis (RA) patients. The prognostic value is also studied in a cohort of patients with early RA. Moreover, we transfer immunological assays from microtiter plates to microarray formats to allow the simultaneous analysis of several peptide sequences and reduce the volume of serum from patients. METHODS The diagnostic study includes: 100 RA patients who fulfilled the 1987 ACR criteria; 100 healthy blood donors; 35 patients with SLE according ACR criteria; 35 patients with PsA fulfilling the Wright and Moll criteria and 30 patients with HCV infection. The prognostic value study includes 50 patients with early RA with follow-up data available. All samples are from outpatients attending the Rheumatology Department of the Hospital Clinic of Barcelona. RESULTS Similar sensitivity, specificity and predictive values for the diagnosis of RA of CCFCPs compared to CCP3/CCP3.1 were obtained. Although a high concordance is observed between anti-CFFCPs and anti-CCP3/CCP3.1 in the early patients that rendered Larsen radiographic progression, CFFCPs could be a better marker of radiographic outcome. Strong correlations between the microarray and ELISA results were found for individual CFFCPs peptides. CONCLUSIONS The development of multiplexing techniques combining a different spectrum of markers in a single analysis, including CFFCP peptides, could allow a more detailed analysis of the autoantibodies reactivity found in the sera of patients suffering of this heterogeneous disease.
Collapse
|
|
12
|
Darawshe S, Watad A, Bragazzi NL, Gertel S, Amital H. The role of synthetic manufactured peptides containing common citrullinated epitopes in rheumatoid arthritis diagnosis. Clin Immunol 2019; 199:7-11. [DOI: 10.1016/j.clim.2018.12.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
|
|
13
|
Ji M, Hur M, Moon HW, Park M, Yun YM, Lee SH. Comparison of second- and third-generation immunoassays for detection of anti-cyclic citrullinated peptide antibodies. Scandinavian Journal of Clinical and Laboratory Investigation 2018; 78:477-482. [PMID: 30073867 DOI: 10.1080/00365513.2018.1499957] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Anti-cyclic citrullinated peptide antibodies (anti-CCPs) are important diagnostic markers for rheumatoid arthritis (RA). We evaluated the analytical and clinical performance of the QUANTA Flash CCP3 (INOVA Diagnostics, USA), a fully automated third-generation anti-CCP assay, in comparison with three second-generation anti-CCP (CCP2) assays. A total of 300 sera (67 from RA patients, 64 from other rheumatic diseases, 43 from osteoarthritis [OA], and 126 from other conditions) were tested with QUANTA Flash CCP3, Kallestad Anti-CCP II (Bio-Rad, USA), Elecsys Anti-CCP (Roche Diagnostics GmbH, Germany), and ARCHITECT Anti-CCP (Abbott Diagnostics, USA). Within-run and total imprecision (% coefficient of variation) of the QUANTA Flash CCP3 were <6%, and its linearity was acceptable over the claimed range (4.0-2,749.7 chemiluminescent units). The frequency of anti-CCP was similar between QUANTA Flash CCP3 and the other CCP2 assays in the RA (67.2% vs. 62.7-70.1%), other rheumatic diseases (7.8% vs. 6.3%), and OA (2.3% vs. 0-2.3%) groups. The concordance rate between QUANTA Flash CCP3 and the other assays ranged from 96.3% to 97.7% (kappa from 0.87 to 0.92). For the diagnosis of RA, the sensitivity/specificity was 67.2%/95.7%, 62.7%/98.3%, 70.2%/96.6%, and 67.2%/97.9%, and the areas under the receiver operating characteristic curves were 0.851, 0.791, 0.853, and 0.867 for QUANTA Flash CCP3, Kallestad, Elecsys, and ARCHITECT assays, respectively. The performance of the QUANTA Flash CCP3 was satisfactory and comparable to that of the three CCP2 assays. This fully automated assay would be a practical and reasonable option in clinical laboratories.
Collapse
Affiliation(s)
- Misuk Ji
- a Department of Laboratory Medicine , Veterans Health Service (VHS) Medical Center , Seoul , Korea
| | - Mina Hur
- b Department of Laboratory Medicine , Konkuk University School of Medicine , Seoul , Korea
| | - Hee-Won Moon
- b Department of Laboratory Medicine , Konkuk University School of Medicine , Seoul , Korea
| | - Mikyoung Park
- b Department of Laboratory Medicine , Konkuk University School of Medicine , Seoul , Korea
| | - Yeo-Min Yun
- b Department of Laboratory Medicine , Konkuk University School of Medicine , Seoul , Korea
| | - Sang-Heon Lee
- c Department of Internal Medicine , Konkuk University School of Medicine , Seoul , Korea
| |
Collapse
|
|
14
|
Kamalaksha S, White DHN, Solanki KK. Significance of combined anti-CCP antibodies and rheumatoid factor in a New Zealand cohort of patients with systemic sclerosis. Int J Rheum Dis 2018; 21:1430-1435. [DOI: 10.1111/1756-185x.13330] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
| | - Douglas H. N. White
- Rheumatology Department; Waikato Hospital; Hamilton New Zealand
- Waikato Clinical School; University of Auckland; Hamilton New Zealand
| | - Kamal K. Solanki
- Rheumatology Department; Waikato Hospital; Hamilton New Zealand
- Waikato Clinical School; University of Auckland; Hamilton New Zealand
| |
Collapse
|
|
15
|
Trier NH, Holm BE, Heiden J, Slot O, Locht H, Jensen B, Lindegaard H, Svendsen A, Nielsen CT, Jacobsen S, Theander E, Houen G. The use of synthetic peptides for detection of anti-citrullinated protein antibodies in rheumatoid arthritis. J Immunol Methods 2018; 454:6-14. [DOI: 10.1016/j.jim.2017.11.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 09/28/2017] [Accepted: 11/06/2017] [Indexed: 11/29/2022]
|
|
16
|
Trier NH, Holm BE, Heiden J, Slot O, Locht H, Lindegaard H, Svendsen A, Nielsen CT, Jacobsen S, Theander E, Houen G. Antibodies to a strain-specific citrullinated Epstein-Barr virus peptide diagnoses rheumatoid arthritis. Sci Rep 2018; 8:3684. [PMID: 29487382 PMCID: PMC5829227 DOI: 10.1038/s41598-018-22058-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Accepted: 02/09/2018] [Indexed: 12/13/2022] Open
Abstract
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Anti-citrullinated protein antibodies (ACPA) are crucial for the serological diagnosis of RA, where Epstein-Barr virus (EBV) has been suggested to be an environmental agent in triggering the onset of the disease. This study aimed to analyse antibody reactivity to citrullinated EBV nuclear antigen-2 (EBNA-2) peptides from three different EBV strains (B95-8, GD1 and AG876) using streptavidin capture enzyme-linked immunosorbent assay. One peptide, only found in a single strain (AG876), obtained a sensitivity and specificity of 77% and 95%, respectively and showed high sequence similarity to the filaggrin peptide originally used for ACPA detection. Comparison of antibody reactivity to commercial assays found that the citrullinated peptide was as effective in detecting ACPA as highly sensitive and specific commercial assays. The data presented demonstrate that the citrullinated EBNA-2 peptide indeed is recognised specifically by RA sera and that the single peptide is able to compete with assays containing multiple peptides. Furthermore, it could be hypothesized that RA may be caused by (a) specific strain(s) of EBV.
Collapse
Affiliation(s)
- Nicole Hartwig Trier
- Department of Autoimmunology and Biomarkers, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark.
| | - Bettina Eide Holm
- Department of Autoimmunology and Biomarkers, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark
| | - Julie Heiden
- Department of Autoimmunology and Biomarkers, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark
| | - Ole Slot
- Department of Rheumatology, Glostrup Hospital, Nordre Ringvej 57, 2600, Glostrup, Denmark
| | - Henning Locht
- Department of Rheumatology, Frederiksberg Hospital, Nordre Fasanvej 57, 2000, Frederiksberg, Denmark
| | - Hanne Lindegaard
- Department of Rheumatology, Odense University Hospital, Søndre Boulevard 29, 5000, Odense C, Denmark
| | - Anders Svendsen
- Epidemiology, Biostatistics and Bio-demography, Institute of Public Health, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark
| | - Christoffer Tandrup Nielsen
- Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark
| | - Søren Jacobsen
- Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark
| | - Elke Theander
- Department of Rheumatology, Skåne University Hospital, Lund University, 20502, Malmö, Sweden
| | - Gunnar Houen
- Department of Autoimmunology and Biomarkers, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark.
| |
Collapse
|
|
17
|
Laustriat G, Ruyssen-Witrand A, Constantin A, Barnetche T, Adoue D, Cantagrel A, Degboé Y. Anti-citrullinated peptides antibodies in systemic sclerosis: Meta-analysis of frequency and meaning. Joint Bone Spine 2017; 85:147-153. [PMID: 29183860 DOI: 10.1016/j.jbspin.2017.11.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 11/05/2017] [Indexed: 01/14/2023]
Abstract
OBJECTIVES Diagnosis of systemic sclerosis (SSc) is partially determined by the presence of specific autoantibodies often associated with specific clinical features. Recent studies report the presence of ACPA in SSc. We aimed to evaluate the prevalence of ACPA in SSc and to assess their influence on clinical presentation of SSc. METHODS A systematic literature search was performed using PubMed and Cochrane databases' publications between 1999 and March 2017. Search terms were: "systemic sclerosis [MeSH] AND (ACPA OR anti-CCP OR rheumatoid factor OR cohort OR value diagnostic)". In a first step, we selected cohorts with >50 SSc patients with ACPA identification, for ACPA frequency determination. In a second step, we included studies that analysed clinical profiles according to ACPA status. Meta-analyses were performed when at least two studies were available. RESULTS First, we identified 13 observational studies with a total of 1231 SSc patients. The mean prevalence of ACPA in SSc was 9.2%. Secondly, we identified nine studies reporting clinical aspects according to ACPA status. Our meta-analyses showed a significant association between ACPA positivity and the presence of arthritis (odds ratio (OR)=22.48 [10.71-47.21]), joint erosions seen on X-rays (OR=14.79 [6.38-34.28]), pulmonary fibrosis (OR=2.75 [1.21-6.24]), oesophagus involvement (OR=2.72 [1.05-7.07]), and diffuse skin involvement (OR=2.21 [1.21-4.03]). CONCLUSIONS The prevalence of ACPA in scleroderma is 9.2%. Our meta-analysis shows an increased risk for erosive arthritis, pulmonary fibrosis, oesophagus involvement and diffuse skin involvement, in patients with ACPA-positive SSc. ACPA should be systematically included in SSc assessment.
Collapse
Affiliation(s)
- Guillaume Laustriat
- Centre de rhumatologie, hôpital Pierre-Paul-Riquet, CHU de Toulouse, place du Dr-Baylac, TSA 40 031, 31059 Toulouse cedex 9, France
| | - Adeline Ruyssen-Witrand
- Centre de rhumatologie, hôpital Pierre-Paul-Riquet, CHU de Toulouse, place du Dr-Baylac, TSA 40 031, 31059 Toulouse cedex 9, France; Pharmaco-épidémiologie, évaluation de l'utilisation et du risque médicamenteux, Inserm UMR 1027, faculté de médecine, 37, allées Jules-Guesde, 31000 Toulouse, France
| | - Arnaud Constantin
- Centre de rhumatologie, hôpital Pierre-Paul-Riquet, CHU de Toulouse, place du Dr-Baylac, TSA 40 031, 31059 Toulouse cedex 9, France; CPTP, Inserm UMR 1043, CHU Purpan, BP 3028, 31024 Toulouse cedex 3, France
| | - Thomas Barnetche
- Service de rhumatologie, FHU Acronim, CHU Pellegrin, place Amélie-Raba-Léon, 33000 Bordeaux, France
| | - Daniel Adoue
- Centre de rhumatologie, hôpital Pierre-Paul-Riquet, CHU de Toulouse, place du Dr-Baylac, TSA 40 031, 31059 Toulouse cedex 9, France; Service d'immunologie clinique, IUCT, oncopole, CHU de Toulouse, 1, avenue Irène-Joliot-Curie, 31059 Toulouse cedex 9, France
| | - Alain Cantagrel
- Centre de rhumatologie, hôpital Pierre-Paul-Riquet, CHU de Toulouse, place du Dr-Baylac, TSA 40 031, 31059 Toulouse cedex 9, France; CPTP, Inserm UMR 1043, CHU Purpan, BP 3028, 31024 Toulouse cedex 3, France
| | - Yannick Degboé
- Centre de rhumatologie, hôpital Pierre-Paul-Riquet, CHU de Toulouse, place du Dr-Baylac, TSA 40 031, 31059 Toulouse cedex 9, France; CPTP, Inserm UMR 1043, CHU Purpan, BP 3028, 31024 Toulouse cedex 3, France.
| |
Collapse
|
|
18
|
Vos I, Van Mol C, Trouw LA, Mahler M, Bakker JA, Van Offel J, De Clerck L, Huizinga TW. Anti-citrullinated protein antibodies in the diagnosis of rheumatoid arthritis (RA): diagnostic performance of automated anti-CCP-2 and anti-CCP-3 antibodies assays. Clin Rheumatol 2017; 36:1487-1492. [PMID: 28578492 PMCID: PMC5486477 DOI: 10.1007/s10067-017-3684-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 05/09/2017] [Accepted: 05/15/2017] [Indexed: 11/26/2022]
Abstract
This study compares the diagnostic performance of a second generation anti-cyclic citrullinated peptide antibody (CCP2) with a third generation anti-CCP antibodies assay (CCP3), as well as the combination of both tests. Serum samples of 127 patients were analyzed. IgG anti-CCP 2 and IgM rheumatoid factor were determined by EliA™ technique on a Phadia 250 instrument (Thermo Fisher Scientific), anti-CCP3 by the Quanta Flash™ anti-CCP3 IgG kit, BIO-FLASH Rapid Response Chemiluminscence Analyzer (INOVA Diagnostics). Diagnostic performance was compared using ROC-curves, sensitivity, specificity, likelihood ratios, and predictive values. Logistic regressions were used to investigate whether using both tests (anti-CCP2 and anti-CCP3) gives a better prediction of rheumatoid arthritis. At the manufacturer’s cut-offs sensitivity and specificity were 79.4 and 61.0% for CCP3 and 80.9 and 69.5% for CCP2. No significant differences could be observed regarding the areas under the curve (AUC) of both ROC-curves. The optimal cut-off point for CCP2 was 10.5 U/ml (sensitivity of 75.0% and specificity of 80.0%) and 5.6 U/ml for CCP3 (sensitivity of 86.9% and specificity of 61.0%). Binary logistic regressions indicated that the likelihood of having rheumatoid arthritis (RA) is significantly higher when testing positive on both CCP2 and CCP3 compared to CCP2 or CCP3 alone. In our cohort, comparable performance was found between the two CCP assays. Positivity for both CCP2 and CCP3 resulted in the most specific identification of RA patients. In patients with joint complaints suspected of having RA and with a weakly positive CCP 2 (≥7 and ≤16 U/ml) CCP3 testing could be of additive value for diagnosing RA.
Collapse
Affiliation(s)
- Ine Vos
- Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.
- Department of Rheumatology, University Hospital of Antwerp, Edegem, Belgium.
| | - Christof Van Mol
- Netherlands Interdisciplinary Demographic Institute/KNAW/UG, The Hague, the Netherlands
| | - Leendert A Trouw
- Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands
| | | | - Jaap A Bakker
- Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands
| | - Jan Van Offel
- Department of Rheumatology, University Hospital of Antwerp, Edegem, Belgium
| | - Luc De Clerck
- Department of Rheumatology, University Hospital of Antwerp, Edegem, Belgium
| | - Tom W Huizinga
- Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands
| |
Collapse
|
|
19
|
Epitope Specificity of Anti-Citrullinated Protein Antibodies. Antibodies (Basel) 2017; 6:antib6010005. [PMID: 31548521 PMCID: PMC6698845 DOI: 10.3390/antib6010005] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Revised: 02/06/2017] [Accepted: 02/22/2017] [Indexed: 01/21/2023] Open
Abstract
Anti-citrullinated protein antibodies are primarily associated with a progressive course in the autoimmune disease rheumatoid arthritis, a disease with a chronic and inflammatory nature. These antibodies do not appear to have any strict dependency for reactivity except from the presence of the non-genetically encoded amino acid citrulline, which is the result of a posttranslational modification, catalyzed by calcium-dependent peptidylarginine deiminase enzymes. Nevertheless, several amino acids surrounding the citrulline residue notably influence antibody reactivity, especially with a central-Cit-Gly-motif being essential for antibody reactivity. Most importantly, these antibodies have been proposed to be divided into two groups, based on their ability to recognize multiple citrullinated peptides. Thus, an "overlapping" antibody group, which appears to recognize several citrullinated peptides, and a "non-overlapping" antibody group, which only recognizes a limited number of citrullinated peptides, have been proposed. Based on these findings, we suggest that antibodies recognizing several citrullinated targets, also referred to as cross-reactive antibodies, primarily are backbone-dependent, whereas less cross-reactive antibodies primarily depend on the side chains of the amino acids comprising the epitopes for stable antibody-antigen interactions, which reduces the degree of cross-reactivity significantly. Clarifying the reactivity pattern of anti-citrullinated protein antibodies may contribute to determining their true nature of origin.
Collapse
|
|
20
|
Abdessemed A, Khaldoun N, Tahiat A, Djidjik R, Mellal Y, Allam I, Slimani S, Haddouche A, Brahimi N, Ghaffor M, Rezig AL. Erosive arthritis and anti-cyclic citrullinated peptide antibodies in systemic sclerosis. INDIAN JOURNAL OF RHEUMATOLOGY 2017. [DOI: 10.4103/injr.injr_46_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
|
|
21
|
Karthikeyan K, Barker K, Tang Y, Kahn P, Wiktor P, Brunner A, Knabben V, Takulapalli B, Buckner J, Nepom G, LaBaer J, Qiu J. A Contra Capture Protein Array Platform for Studying Post-translationally Modified (PTM) Auto-antigenomes. Mol Cell Proteomics 2016; 15:2324-37. [PMID: 27141097 PMCID: PMC4937507 DOI: 10.1074/mcp.m115.057661] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2015] [Revised: 04/19/2016] [Indexed: 11/06/2022] Open
Abstract
Aberrant modifications of proteins occur during disease development and elicit disease-specific antibody responses. We have developed a protein array platform that enables the modification of many proteins in parallel and assesses their immunogenicity without the need to express, purify, and modify proteins individually. We used anticitrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) as a model modification and profiled antibody responses to ∼190 citrullinated proteins in 20 RA patients. We observed unique antibody reactivity patterns in both clinical anticyclic citrullinated peptide assay positive (CCP+) and CCP- RA patients. At individual antigen levels, we detected antibodies against known citrullinated autoantigens and discovered and validated five novel antibodies against specific citrullinated antigens (osteopontin (SPP1), flap endonuclease (FEN1), insulin like growth factor binding protein 6 (IGFBP6), insulin like growth factor I (IGF1) and stanniocalcin-2 (STC2)) in RA patients. We also demonstrated the utility of our innovative array platform in the identification of immune-dominant epitope(s) for citrullinated antigens. We believe our platform will promote the study of post-translationally modified antigens at a breadth that has not been achieved before, by both identifying novel autoantigens and investigating their roles in disease development. The developed platforms can potentially be used to study many autoimmune disease-relevant modifications and their immunogenicity.
Collapse
Affiliation(s)
- Kailash Karthikeyan
- From the ‡Biodesign Institute, Center for Personalized Diagnostics, Arizona State University, Tempe, Arizona 85287
| | - Kristi Barker
- From the ‡Biodesign Institute, Center for Personalized Diagnostics, Arizona State University, Tempe, Arizona 85287
| | - Yanyang Tang
- From the ‡Biodesign Institute, Center for Personalized Diagnostics, Arizona State University, Tempe, Arizona 85287
| | - Peter Kahn
- §Engineering Arts LLC, Phoenix, Arizona 85076
| | - Peter Wiktor
- From the ‡Biodesign Institute, Center for Personalized Diagnostics, Arizona State University, Tempe, Arizona 85287; §Engineering Arts LLC, Phoenix, Arizona 85076
| | - Al Brunner
- §Engineering Arts LLC, Phoenix, Arizona 85076
| | - Vinicius Knabben
- From the ‡Biodesign Institute, Center for Personalized Diagnostics, Arizona State University, Tempe, Arizona 85287
| | - Bharath Takulapalli
- From the ‡Biodesign Institute, Center for Personalized Diagnostics, Arizona State University, Tempe, Arizona 85287
| | - Jane Buckner
- ¶Benaroya Research Institute, Seattle, Washington 98101
| | - Gerald Nepom
- ¶Benaroya Research Institute, Seattle, Washington 98101
| | - Joshua LaBaer
- From the ‡Biodesign Institute, Center for Personalized Diagnostics, Arizona State University, Tempe, Arizona 85287
| | - Ji Qiu
- From the ‡Biodesign Institute, Center for Personalized Diagnostics, Arizona State University, Tempe, Arizona 85287;
| |
Collapse
|
|
22
|
Abstract
BACKGROUND Anti-citrullinated protein antibodies (ACPAs) are important for the detection of rheumatoid arthritis (RA). There are many laboratories to detect it in their routine work, but their performance is not displayed in China. To examine the performance of ACPA assays from all laboratories, it is necessary to organize a laboratory proficiency test (PT). METHODS A panel of 5 samples, including 4 positive and 1 negative, was produced by the National Center for Clinical Laboratories, using serum derived from patients, then distributed to 271 clinical laboratories. Quantitative and qualitative results reported by the participating laboratories were compared. RESULTS Overall, 80.97% (200/247) of the laboratories had eligible PT scores. Of the kits used, most ELISA and chemiluminescence kits had a high sensitivity and specificity. Regarding intra-assay discrepancy, the Roche and Abbott kit had a better variable coefficient. The ratios of the quantitative results to the kit-specific cut-off values were similar. CONCLUSION Performance varied between laboratories. Reagents and methods are the most important factors. Other factors may affect the intra-assay discrepancy. The similar mean of ratios of the quantitative results to the kit-assigned cut-offs suggests that a national criterion is requisite. It is necessary to organize a PT to identify performances of different laboratories.
Collapse
|
|
23
|
Dionello CF, Rosa Utiyama SR, Radominski SC, Stahlke E, Stinghen ST, de Messias-Reason IJ. Evaluation of rheumatoid factor and anti-citrullinated peptide antibodies in relation to rheumatological manifestations in patients with leprosy from Southern Brazil. Int J Rheum Dis 2015; 19:1024-1031. [PMID: 26250118 DOI: 10.1111/1756-185x.12668] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Leprosy patients may present several osteoarticular complaints, which require further evaluation of inflammatory diseases, such as rheumatoid arthritis (RA). Therefore, an adequate clinical assessment in addition to testing for rheumatoid factors (RF) and anticyclic citrullinated peptide antibodies (anti-CCP), can be useful in order to establish the correct diagnosis. METHOD In this study, the relation of RF and anti-CCP with rheumatological manifestations was evaluated in 97 leprosy patients from Southern Brazil. The results were compared to RA patients and healthy controls from the same geographical area and ethnic background. RESULTS Neuropathy was observed in 71.1% and arthritis in 35.1% of the leprosy patients. A high frequency of RF positivity was observed among the leprosy patients (41.2%, 40/97), with RF immunoglobulin A (IgA) significantly associated with arthritis (OR = 7.9, 95% CI = 1.5-40.6 P = 0.008). Anti-CCP was observed in 9.3% (9/97) of the patients, with anti-CCP2 being the most frequent subtype. Only 4.1% (4/97) of the patients were RF and anti-CCP concomitantly positive. RF IgM showed a significant association with leprosy when compared to healthy controls (P < 0.0001) whereas for anti-CCP2 no significant results were observed (P = 0.0585). However, both biomarkers showed a strong association with RA when compared to leprosy in patients from the same geographical area and ethnic background (anti-CCP2 OR = 38.6; 95% CI = 16.49-90.26; P < 0.0001 and RF IgM OR = 4.51; 95% CI = 2.62-7.77; P < 0.0001). CONCLUSION Due to the similarity of some rheumatological manifestations in leprosy with other inflammatory diseases, such as RA, clinical and laboratorial evaluation of affected patients must be carefully assessed in order to achieve proper diagnosis and treatment.
Collapse
Affiliation(s)
- Carla Fontoura Dionello
- Laboratório de Imunopatologia, Departamento de Patologia Médica, Clinical Hospital of Federal University of Parana, Curitiba, Brazil
| | - Shirley Ramos Rosa Utiyama
- Laboratório de Imunopatologia, Departamento de Patologia Médica, Clinical Hospital of Federal University of Parana, Curitiba, Brazil
| | | | - Ewalda Stahlke
- Setor de Dermatologia, Centro Regional de Especialidades Metropolitano de Curitiba, Curitiba, Brazil
| | - Servio Tulio Stinghen
- Laboratório de Imunopatologia, Departamento de Patologia Médica, Clinical Hospital of Federal University of Parana, Curitiba, Brazil
| | - Iara Jose de Messias-Reason
- Laboratório de Imunopatologia, Departamento de Patologia Médica, Clinical Hospital of Federal University of Parana, Curitiba, Brazil.
| |
Collapse
|
|
24
|
Immunodiagnostic significance of anti-RA33 autoantibodies in Saudi patients with rheumatoid arthritis. J Immunol Res 2015; 2015:604305. [PMID: 25883991 PMCID: PMC4389979 DOI: 10.1155/2015/604305] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2014] [Revised: 03/09/2015] [Accepted: 03/15/2015] [Indexed: 11/17/2022] Open
Abstract
The primary objective of this study was to evaluate and compare the immunodiagnostic significance and utility of anti-RA33 with anti-CCP, RF, and CRP in Saudi patients with rheumatoid arthritis. Methods. This was a prospective controlled clinical study conducted at King Abdul Aziz University Tertiary Medical Centre. The sera of 41 RA patients, 31 non-RA patients, and 29 healthy controls were collected. Anti-RA33 and anti-CCP were measured using commercially available ELISA principle kits. RF and CRP were measured using nephelometry. Results. Anti-RA33 antibodies had the lowest positive and negative predictive values and showed a sensitivity of 7.32% with 95.12% specificity. Of the other three markers (including anti-CCP antibodies, CRP, and RF), only anti-CCP showed specificity of 90.46% with sensitivity of 63.41% compared to non-RA patients + healthy control. There was a significant correlation with rheumatoid factor positivity with anti-CCP. With respect to CRP, a notable correlation was seen only with anti-RA33. Conclusion. Compared to rheumatoid factor, anti-CCP antibodies, and C-reactive proteins, the anti-RA33 autoantibodies seem to be not representing as an important additional immunodiagnostic marker in Saudi patients with established RA. RA33 may have more interest in early RA or less severe RA and other systemic connective tissue disorders.
Collapse
|
|
25
|
Senécal JL, Isabelle C, Fritzler MJ, Targoff IN, Goldstein R, Gagné M, Raynauld JP, Joyal F, Troyanov Y, Dabauvalle MC. An autoimmune myositis-overlap syndrome associated with autoantibodies to nuclear pore complexes: description and long-term follow-up of the anti-Nup syndrome. Medicine (Baltimore) 2014; 93:383-394. [PMID: 25500708 PMCID: PMC4602431 DOI: 10.1097/md.0000000000000223] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss. The myositis was typically chronic, relapsing, and refractory to corticosteroids alone, but remitted with the addition of a second immunomodulating drug. There was no clinical or laboratory evidence for liver disease. The prognosis was good with 100% long-term survival (mean follow-up 19.5 yr).By indirect immunofluorescence on HEp-2 cells, sera from all 4 patients displayed a high titer of antinuclear autoantibodies (ANA) with a distinct punctate peripheral (rim) fluorescent pattern of the nuclear envelope characteristic of nuclear pore complexes. Reactivity with nuclear pore complexes was confirmed by immunoelectron microscopy. In a cohort of 100 French Canadian patients with autoimmune myositis, the nuclear pore complex fluorescent ANA pattern was restricted to these 4 patients (4%). It was not observed in sera from 393 adult patients with systemic sclerosis (n = 112), mixed connective tissue disease (n = 35), systemic lupus (n = 94), rheumatoid arthritis (n = 45), or other rheumatic diseases (n = 107), nor was it observed in 62 normal adults.Autoantibodies to nuclear pore complexes were predominantly of IgG isotype. No other IgG autoantibody markers for defined connective tissue diseases or overlap syndromes were present, indicating a selective and highly focused immune response. In 3 patients, anti-nuclear pore complex autoantibody titers varied in parallel with myositis activity, suggesting a pathogenic link to pathophysiology. The nuclear pore complex proteins, that is, nucleoporins (nup), recognized by these sera were heterogeneous and included Nup358/RanBP2 (n = 2 patients), Nup90 (n = 1), Nup62 (n = 1), and gp210 (n = 1). Taken together the data suggest that nup autoantigens themselves drive the anti-nup autoimmune response. Immunogenetically, the 4 patients shared the DQA1*0501 allele associated with an increased risk for autoimmune myositis.In conclusion, we report an apparent novel subset of autoimmune myositis in our population of French Canadian patients with connective tissue diseases. This syndrome is recognized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes that react with nups, consistent with an "anti-nup syndrome."
Collapse
Affiliation(s)
- Jean-Luc Senécal
- From the Department of Medicine, Divisions of Rheumatology (JLS, CI, JPR, YT) and Internal Medicine (FJ), and Laboratory for Research in Autoimmunity, Research Center of the Centre Hospitalier de l'Université de Montréal, University of Montreal Faculty of Medicine, Montreal, Quebec, Canada; Mitogen Advanced Diagnostics Laboratory (MJF), Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; Veterans Affairs Medical Center (INT), University of Oklahoma Health Sciences Center, and Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States; McGill University (RG), Montreal, Quebec, Canada; Polyclinique Saint-Eustache (MG), Saint-Eustache, Quebec, Canada; Biocenter (MCD), Division of Electron Microscopy, University of Würzburg, Am Hubland, Würzburg, Germany
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
26
|
Webb T, Lakos G, Swart A, Gürtler I, Favalli EG, Schioppo T, Mahler M. Clinical evaluation of a novel chemiluminescent immunoassay for the detection of anti-citrullinated peptide antibodies. Clin Chim Acta 2014; 437:161-7. [DOI: 10.1016/j.cca.2014.07.032] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2014] [Revised: 07/23/2014] [Accepted: 07/23/2014] [Indexed: 11/29/2022]
|
|
27
|
Payet J, Goulvestre C, Bialé L, Avouac J, Wipff J, Job-Deslandre C, Batteux F, Dougados M, Kahan A, Allanore Y. Anticyclic Citrullinated Peptide Antibodies in Rheumatoid and Nonrheumatoid Rheumatic Disorders: Experience with 1162 Patients. J Rheumatol 2014; 41:2395-402. [DOI: 10.3899/jrheum.131375] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Objective.Anticyclic citrullinated peptide antibodies (anti-CCP) are considered specific markers of rheumatoid arthritis (RA) and have been included in the revised classification criteria for RA diagnosis. However, these antibodies have also been detected in patients with other types of chronic inflammatory rheumatism. Our objectives were to identify the prevalence of positive anti-CCP patients in non-RA diseases, to determine the diagnostic value of anti-CCP for the diagnosis of RA, to specify the clinical characteristics of non-RA patients positive for anti-CCP, and to determine the discriminatory value of the levels of anti-CCP in patients among the various diseases.Methods.We carried out an observational and descriptive study. All the determinations of anti-CCP requested by the 2 rheumatology departments at Cochin Hospital over a period of 18 months were analyzed. Such determinations were requested for 1162 patients in total. Anti-CCP levels were determined with the Euro Diagnostica ELISA kit, with values ≥ 25 U for this test being considered positive. The diagnosis of rheumatic conditions was the responsibility of the treating physician.Results.Anti-CCP antibodies were detected in 357 (30.7%) of the 1162 patients. The prevalence of anti-CCP was 292/417 (70.0%) in RA, 13/122 (10.6%) in patients with psoriatic arthritis, 13/62 (20.9%) in patients with unclassified rheumatism, 11/33 (33.3%) in patients with primary Sjögren syndrome, 5/30 (16.6%) in patients with systemic lupus erythematosus, 3/28 (10.7%) in patients with mixed connective tissue disorder, 3/36 (8.3%) in patients with systemic sclerosis, 7/44 (15.9%) in patients with juvenile arthritis, and 6/220 (2.7%) in patients with noninflammatory diseases. In the population of patients positive for anti-CCP, mean anti-CCP levels were 869.4 (± 978.4) U/ml, with no significant difference between RA [854.8 (± 959.8) U/ml] and any of the non-RA conditions [922.7 (± 1070.0) U/ml].Conclusion.Anti-CCP are a hallmark of RA, but may be observed in other inflammatory, systemic, or mechanical diseases. In this large cohort of patients, the presence of second-generation anti-CCP (anti-CCP2) antibodies is useful in diagnosing RA (70% sensitivity, 91.3% specificity), but examining the levels of these antibodies does not appear to offer further discriminatory power among patients who are anti-CCP2-positive.
Collapse
|
|
28
|
Yamagiwa S, Kamimura H, Takamura M, Aoyagi Y. Autoantibodies in primary biliary cirrhosis: recent progress in research on the pathogenetic and clinical significance. World J Gastroenterol 2014; 20:2606-2612. [PMID: 24627596 PMCID: PMC3949269 DOI: 10.3748/wjg.v20.i10.2606] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2013] [Revised: 11/22/2013] [Accepted: 01/08/2014] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic liver disease characterized by immune-mediated destruction of the small- and medium-sized intrahepatic bile ducts and the presence of antimitochondrial antibodies (AMA) in the serum. AMA are detected in over 90% of patients with PBC, whereas their prevalence in the general population is extremely low, varying from 0.16% to 1%. Previous studies have shown that the unique characteristics of biliary epithelial cells undergoing apoptosis may result in a highly direct and very specific immune response to mitochondrial autoantigens. Moreover, recent studies have demonstrated that serum from AMA-positive PBC patients is reactive with a number of xenobiotic modified E2 subunits of the pyruvate dehydrogenase complex, which is not observed in the serum of normal individuals. These findings indicate that chemicals originating from the environment may be associated with a breakdown in the tolerance to mitochondrial autoantigens. While it is currently generally accepted that AMA are the most specific serological markers of PBC, more than 60 autoantibodies have been investigated in patients with PBC, and some have previously been considered specific to other autoimmune diseases. This review covers the recent progress in research on the pathogenetic and clinical significance of important autoantibodies in PBC. Determining the pathogenic role of those autoantibodies in PBC remains a priority of basic and clinical research.
Collapse
|
|
29
|
Terao C, Ohmura K, Kawaguchi Y, Nishimoto T, Kawasaki A, Takehara K, Furukawa H, Kochi Y, Ota Y, Ikari K, Sato S, Tohma S, Yamada R, Yamamoto K, Kubo M, Yamanaka H, Kuwana M, Tsuchiya N, Matsuda F, Mimori T. PLD4 as a novel susceptibility gene for systemic sclerosis in a Japanese population. ACTA ACUST UNITED AC 2013; 65:472-80. [PMID: 23124809 DOI: 10.1002/art.37777] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2012] [Accepted: 10/23/2012] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Systemic sclerosis (SSc) is an autoimmune disease for which multiple susceptibility genes have been reported. Genome-wide association studies have shown that large numbers of susceptibility genes are shared among autoimmune diseases. Recently, our group identified 9 novel susceptibility genes associated with rheumatoid arthritis (RA) in a Japanese population. The aim of this study was to elucidate whether the 18 genes that displayed associations or suggestive associations for RA in our previous study are associated with SSc in Japanese. METHODS We performed an association study that included 415 patients with SSc and 16,891 control subjects, followed by a replication study that included 315 patients and 21,054 control subjects. The 18 markers reported to display association with RA were analyzed for their associations with SSc in the first study, and 5 markers were further analyzed in the replication study. The inverse variance method was used to evaluate the associations of these markers with SSc in a combined study. RESULTS In the phospholipase D4 gene (PLD4), rs2841277 displayed a significant association with SSc in Japanese patients (P = 0.00017). We observed that rs2841280 in exon 2 of PLD4 was in strong linkage disequilibrium with rs2841277 and introduced an amino acid alteration. We also observed associations between SSc and rs6932056 in TNFAIP3 and rs2280381 in IRF8 (P = 0.0000095 and P = 0.0030, respectively), both of which displayed associations with SSc in a European population. CONCLUSION We determined that PLD4 is a novel susceptibility gene for SSc in Japanese, thus confirming the involvement of PLD4 in autoimmunity. Associations between SSc and TNFAIP3 or IRF8 were also detected in our Japanese population. SSc and RA appear to share relatively large proportions of their genetic backgrounds.
Collapse
|
|
30
|
The antibodies cyclic citrullinated peptides (anti-CCP) positivity could be a promising marker in brucellosis patients presented with peripheric arthritis. Mod Rheumatol 2013. [DOI: 10.1007/s10165-013-0857-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
|
|
31
|
|
|
32
|
Abdel-Magied RA, Lotfi A, AbdelGawad EA. Magnetic resonance imaging versus musculoskeletal ultrasonography in detecting inflammatory arthropathy in systemic sclerosis patients with hand arthralgia. Rheumatol Int 2013; 33:1961-6. [PMID: 23354165 PMCID: PMC3719002 DOI: 10.1007/s00296-013-2665-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2012] [Accepted: 01/04/2013] [Indexed: 11/30/2022]
Abstract
The aim of the study was the detection of inflammatory arthropathy in patients with systemic sclerosis (SSc) with arthralgia using musculoskeletal ultrasonography (MSUS) and magnetic resonance imaging (MRI) and to compare between MRI versus MSUS detecting musculoskeletal abnormalities and find out its relation with other clinical and laboratory parameters. Sixteen SSc patients with hand arthralgia had a baseline MSUS for their hands. Six months later, patients had a second MSUS and MRI with gadolinium of their most symptomatic hand. Of the 16 patients examined by MSUS, it was found that on baseline and second examination, tenosynovitis was seen in 8 (50 %) and 7 (43.7 %) patients and synovitis was seen in 4 (25 %) and 5 (31 %) patients, respectively, indicating persistence synovial inflammation, and erosion was seen in only 1 (6.3 %) patient on baseline and second examination. Regarding MRI, 81.3 % (13) patients had tenosynovitis, 87.5 % (14) patients had synovitis, and 62.5 % (10) patients had erosions. Applying the RAMRIS system (a semiquantitative MRI scoring system used in RA), the mean values for synovitis, bone marrow edema, and erosions fell within the range seen in RA. Systemic sclerosis patients with arthralgia that have no obvious clinical inflammatory arthritis were found to have persistent inflammatory erosive arthropathy in their hands and wrists using MSUS and MRI. While both MRI and MSUS are useful in characterizing synovial inflammation in SSc, MRI is clearly more sensitive than MSUS in this setting. Further studies on larger number of SSc patients with arthralgia and a control group consisting of SSc patients without arthralgia to better establish the clinical and radiological findings in SSc.
Collapse
|
|
33
|
Lima I, Oliveira RC, Atta A, Marchi S, Barbosa L, Reis E, Reis MG, Santiago MB. Antibodies to citrullinated peptides in tuberculosis. Clin Rheumatol 2013; 32:685-7. [DOI: 10.1007/s10067-013-2173-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2012] [Revised: 12/13/2012] [Accepted: 01/11/2013] [Indexed: 12/01/2022]
|
|
34
|
Mehra S, Walker J, Patterson K, Fritzler MJ. Autoantibodies in systemic sclerosis. Autoimmun Rev 2013; 12:340-54. [DOI: 10.1016/j.autrev.2012.05.011] [Citation(s) in RCA: 160] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2012] [Accepted: 05/15/2012] [Indexed: 01/06/2023]
|
|
35
|
Trouw LA, Mahler M. Closing the serological gap: promising novel biomarkers for the early diagnosis of rheumatoid arthritis. Autoimmun Rev 2012; 12:318-22. [DOI: 10.1016/j.autrev.2012.05.007] [Citation(s) in RCA: 107] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Accepted: 05/27/2012] [Indexed: 12/12/2022]
|
|
36
|
Abstract
Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic autoimmune liver disease characterized by the destruction of small intrahepatic bile ducts and the presence of highly specific serum antimitochondrial antibodies (AMAs). The human leukocyte antigen (HLA) gene has been proved to have strongest association with PBC susceptibility, and non-HLA genes, including IL12A, IL12RB2, STAT4, IRF5-TNPO3, ORMDL3/IKZF3, MMEL1, SPIB, CTLA-4, FCRL3 and A2BP1, are also closely associated with PBC susceptibility. Four AMAs including anti-M2, anti-M4, anti-M8 and anti-M9, and antinuclear antibodies (ANAs), such as antinuclear dot antibodies (SP100, PML, NDP52, SP140), antinuclear pore antibodies (gp210, p62), antinuclear envelope antibodies (Lamin and Lamin B receptor), and anti-centromere antibodies, may also be involved in the pathogenesis of PBC. The imbalance between Th17 cells and regulatory T lymphocytes (Treg) may also play an important role in the pathogenesis of PBC. In addition, senescence, autophagy, apoptosis of biliary epithelial cells (BECs), and environmental factors, such as Epstein-Barr virus (EBV) infection and smoking, may also contribute to the pathogenesis of PBC. Understanding of the mechanisms responsible for the pathogenesis of PBC has important implications for the treatment of PBC.
Collapse
|
|
37
|
Swart A, Burlingame RW, Gürtler I, Mahler M. Third generation anti-citrullinated peptide antibody assay is a sensitive marker in rheumatoid factor negative rheumatoid arthritis. Clin Chim Acta 2012; 414:266-72. [PMID: 23022338 DOI: 10.1016/j.cca.2012.09.015] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2012] [Revised: 08/27/2012] [Accepted: 09/14/2012] [Indexed: 11/30/2022]
Abstract
INTRODUCTION We compared 2 anti-citrullinated protein antibody (ACPA) assays using a routine patient cohort. METHODS Two-hundred ninety-five sera were collected from patients for whom ACPA was ordered and tested for ACPA by QUANTA Lite® CCP 3 (INOVA Diagnostics, Inc., San Diego) and EliA® CCP (CCP, Phadia, Germany). Rheumatoid factor (RF) was determined using Quantex RF(II) (Biokit, Spain). RESULTS Acceptable qualitative (96.6%, kappa=0.93) and quantitative agreements (Spearman rho=0.77; p<0.0001) were observed between the two ACPA assays. Nine samples were CCP3+/CCP2- and one sample was CCP2+/CCP3-. Of the 9 CCP3+/CCP2- patients, 6 (66.7%) had RA, one patient had ankylosing spondylitis, one osteoarthritis and one psoriatic arthritis. The CCP3-/CCP2+ patient had juvenile RA. At the manufacturer's cut-offs, the sensitivities and specificities were 77.3%/98.1% (CCP2), 81.6%/96.8% (CCP3) and 65.2%/89.6% (RF), respectively. At 98.7% specificity level, the sensitivities in the total cohort were 59.6% (CCP2) and 69.5% (CCP3) while the sensitivities in the RF-negative group were 49.0% (CCP2) and 57.1% (CCP3). In the RF-negative group, sensitivities for patients with a disease duration of ≤ 5years were 38.7% (CCP2) and 51.6% (CCP3). CONCLUSION Discrimination between RA and non-RA patients was better using CCP3, most pronounced in RF-negative RA.
Collapse
|
|
38
|
Overlap connective tissue disease syndromes. Autoimmun Rev 2012; 12:363-73. [PMID: 22743033 DOI: 10.1016/j.autrev.2012.06.004] [Citation(s) in RCA: 115] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2012] [Accepted: 06/12/2012] [Indexed: 02/06/2023]
Abstract
Overlap Syndromes (OSs) have been defined as entities satisfying classification criteria of at least two connective tissue diseases (CTDs) occurring at the same or at different times in the same patient. CTDs include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), polymyositis/dermatomyositis (PDM), and Sjögren syndrome (SS). Every combination between these disorders has been reported. In some OS a specific autoantibody has been indentified, supporting the hypothesis that these syndromes are not a mere association of two or more CTD in the same patient, but a well defined clinical entity with specific clinical characteristics. As an example, anti-t-RNA synthetase syndrome is characterized by the presence of anti-t-RNA synthetase antibodies. Notably, clinical manifestations observed in OS may be different from those observed in the single CTD. The treatment of OS is mainly based on the use of corticosteroids and immunosuppressants. Biologic drugs, i.e. anti-TNFα or anti-CD20 monoclonal antibodies, have been recently introduced as alternative treatments in refractory cases. Moreover, there are some concerns with the use of anti-TNF agents in patients with systemic autoimmune diseases due to the risk of triggering disease exacerbations. In this paper the most frequent OS are described with a special focus on the specific immunologic and clinical aspects. Furthermore, some personal data on anti-t-RNA synthetase syndrome and rhupus syndrome are reported.
Collapse
|
|
39
|
Gilliam BE, Moore TL. The role of anti-cyclic citrullinated peptide (CCP) antibodies in early detection of rheumatoid arthritis: an overview of the INOVA Diagnostics, Inc. QUANTA Lite CCP assays. ACTA ACUST UNITED AC 2012; 6:359-69. [PMID: 23480744 DOI: 10.1517/17530059.2012.694423] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
INTRODUCTION Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and the presence of self-reactive autoantibodies. Since the discovery of anti-cyclic citrullinated peptide (anti-CCP) antibodies, several assays have been developed to measure these autoantibodies in RA patients. The first-generation kit offered high specificity, but sensitivity was low. The second-generation IgG anti-CCP antibody assay (CCP2) offered the same high specificity, with greatly improved sensitivity for RA. INOVA Diagnostics, Inc. offers, in addition to CCP2, a third-generation assay with higher sensitivity compared with CCP2 and also a combined IgG/IgA anti-CCP antibody assay. AREAS COVERED The review covers the use of INOVA Diagnostics, Inc. multiple anti-CCP antibody assays in early detection of RA, while also comparing these assays with other commercially available methods of measuring anti-CCP antibodies. While most of the review focuses on the significance of these autoantibodies in adult RA patients, their role in juvenile idiopathic arthritis is also discussed. EXPERT OPINION Detection of anti-CCP antibodies has emerged as one of the most important disease markers in RA patients. Several methods are available to measure anti-CCP antibodies, and isotyping and identification of citrullination targets are now the next step in further characterizing these autoantibodies.
Collapse
Affiliation(s)
- Brooke E Gilliam
- Saint Louis University School of Medicine, Division of Adult and Pediatric Rheumatology , 1402 South Grand Blvd, Saint Louis, MI 63104 , USA
| | | |
Collapse
|
|
40
|
Newkirk MM, Mitchell S, Procino M, Li Z, Cosio M, Mazur W, Kinnula VL, Hudson M, Baron M, Fritzler MJ, El-Gabalawy HS. Chronic smoke exposure induces rheumatoid factor and anti-heat shock protein 70 autoantibodies in susceptible mice and humans with lung disease. Eur J Immunol 2012; 42:1051-61. [PMID: 22531929 DOI: 10.1002/eji.201141856] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
The impact of cigarette smoke (CS), a risk factor for rheumatoid arthritis (RA), on sauto-antibody production was studied in humans and mice with and without chronic lung disease (LD). Rheumatoid factor (RF), anti-cyclic citrullinated peptides (CCPs), and anti-HSP70 autoantibodies were measured in several mouse strains and in cohorts of smokers and nonsmokers with and without autoimmune disease. Chronic smoking-induced RFs in AKR/J mice, which are most susceptible to LD. RFs were identified in human smokers, preferentially in those with LD. Anti-HSP70 auto-antibodies were identified in CS-exposed AKR/J mice but not in ambient air exposed AKR/J controls. Whereas inflammation could induce anti-HSP70 IgM, smoke exposure promoted the switch to anti-HSP70 IgG autoantibodies. Elevated anti-CCP autoantibodies were not detected in CS-exposed mice or smokers. AKR/J splenocytes stimulated in vitro by immune complexes (ICs) of HSP70/anti-HSP70 antibodies produced RFs. The CD91 scavenger pathway was required as anti-CD91 blocked the HSP70-IC-induced RF response. Blocking Toll-like receptors did not influence the HSP70-IC-induced RFs. These studies identify both anti-HSP70 and RFs as serological markers of smoke-related LD in humans and mice. Identification of these autoantibodies could suggest a common environmental insult, namely CS, in a number of different disease settings.
Collapse
Affiliation(s)
- Marianna M Newkirk
- Department of Medicine, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
41
|
Bizzaro N, Covini G, Rosina F, Muratori P, Tonutti E, Villalta D, Pesente F, Alessio MG, Tampoia M, Antico A, Platzgummer S, Porcelli B, Terzuoli L, Liguori M, Bassetti D, Brusca I, Almasio PL, Tarantino G, Bonaguri C, Agostinis P, Bredi E, Tozzoli R, Invernizzi P, Selmi C. Overcoming a "probable" diagnosis in antimitochondrial antibody negative primary biliary cirrhosis: study of 100 sera and review of the literature. Clin Rev Allergy Immunol 2012; 42:288-297. [PMID: 21188646 DOI: 10.1007/s12016-010-8234-y] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Serum anti-mitochondrial antibodies (AMA) are the serological hallmark of primary biliary cirrhosis (PBC), yet up to 15% of PBC sera are AMA negative at routine indirect immunofluorescence (IIF) while being referred to as "probable" cases. The diagnostic role of PBC-specific antinuclear antibodies (ANA) remains to be determined. We will report herein data on the accuracy of new laboratory tools for AMA and PBC-specific ANA in a large series of PBC sera that were AMA-negative at IIF. We will also provide a discussion of the history and current status of AMA detection methods. We included IIF AMA-negative PBC sera (n=100) and sera from patients with other chronic liver diseases (n=104) that had been independently tested for IIF AMA and ANA; sera were blindly tested with an ELISA PBC screening test including two ANA (gp210, sp100) and a triple (pMIT3) AMA recombinant antigens. Among IIF AMA-negative sera, 43/100 (43%) manifested reactivity using the PBC screening test. The same test was positive for 6/104 (5.8%) control sera. IIF AMA-negative/PBC screen-positive sera reacted against pMIT3 (11/43), gp210 (8/43), Sp100 (17/43), both pMIT3 and gp210 (1/43), or both pMIT3 and Sp100 (6/43). Concordance rates between the ANA pattern on HEp-2 cells and specific Sp100 and gp210 ELISA results in AMA-negative subjects were 92% for nuclear dots and Sp100 and 99% for nuclear rim and gp210. Our data confirm the hypothesis that a substantial part of IIF AMA-negative (formerly coined "probable") PBC cases manifest disease-specific autoantibodies when tested using newly available tools and thus overcome the previously suggested diagnostic classification. As suggested by the recent literature, we are convinced that the proportion of AMA-negative PBC cases will be significantly minimized by the use of new laboratory methods and recombinant antigens.
Collapse
Affiliation(s)
- Nicola Bizzaro
- Laboratorio di Patologia Clinica, Ospedale Civile, Tolmezzo, Italy.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
42
|
Avouac J, Clements PJ, Khanna D, Furst DE, Allanore Y. Articular involvement in systemic sclerosis. Rheumatology (Oxford) 2012; 51:1347-56. [DOI: 10.1093/rheumatology/kes041] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
|
|
43
|
Anti-cyclic citrullinated peptide antibodies in scleroderma patients. Clin Rheumatol 2012; 31:877-80. [DOI: 10.1007/s10067-011-1930-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2011] [Revised: 10/18/2011] [Accepted: 12/22/2011] [Indexed: 02/02/2023]
|
|
44
|
Demoruelle MK, Deane K. Antibodies to citrullinated protein antigens (ACPAs): clinical and pathophysiologic significance. Curr Rheumatol Rep 2012; 13:421-30. [PMID: 21713412 DOI: 10.1007/s11926-011-0193-7] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Antibodies to citrullinated protein antigens (ACPAs) are highly specific for rheumatoid arthritis (RA) and are useful in the diagnosis of RA as well as the prediction of the course and outcomes of disease. Multiple methodologies exist for measuring ACPAs, including the widely available tests for anticyclic citrullinated peptide antibodies and for antibodies to mutated/modified citrullinated vimentin. These methodologies overall have similar diagnostic accuracies for RA, although there is some variability. The discovery of ACPAs and the biology of citrullination have also led to important advances in the understanding of the pathophysiology and development of RA, especially regarding the relationship between potential genetic and environmental risk factors for RA. Going forward, research into autoimmunity to citrullinated proteins may help identify the specific etiology of RA and provide approaches for the prediction of future risk of disease, and ultimately prevention of RA.
Collapse
Affiliation(s)
- M Kristen Demoruelle
- Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | | |
Collapse
|
|
45
|
Cartilage Oligomeric Matrix Protein (COMP) in systemic sclerosis (SSc): Role in disease severity and subclinical rheumatoid arthritis overlap. Joint Bone Spine 2012; 79:51-6. [DOI: 10.1016/j.jbspin.2011.02.022] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2010] [Accepted: 02/23/2011] [Indexed: 11/20/2022]
|
|
46
|
Clements PJ, Allanore Y, Khanna D, Singh M, Furst DE. Arthritis in systemic sclerosis: systematic review of the literature and suggestions for the performance of future clinical trials in systemic sclerosis arthritis. Semin Arthritis Rheum 2011; 41:801-14. [PMID: 22177105 DOI: 10.1016/j.semarthrit.2011.10.003] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2011] [Revised: 08/22/2011] [Accepted: 10/04/2011] [Indexed: 11/25/2022]
Abstract
OBJECTIVES Musculoskeletal (MSK) pain is a frequent (between 40-80%) complaint of patients with systemic sclerosis (SSc). Unfortunately, there are virtually no systematic studies of the causes or the management of MSK involvement in SSc and with few exceptions there have been no controlled trials to determine what are and should be the best strategies for managing MSK pain and synovitis in patients with SSc. METHODS A literature search was conducted for published reports that have addressed the clinical assessment of "arthritis" and "musculoskeletal" involvement in SSc. The literature search was a prelude to developing recommendations/suggestions for performing clinical trials (preferably randomized) in the future in SSc-related arthritis. RESULTS The search netted a number of articles that reported clinical assessments of arthritis in SSc, but very few reported results of controlled clinical trials. Nevertheless, a prevalence of clinical arthritis and tools used to assess the involvement (clinical examination, functional assessments and assessments of quality of life, and radiographic imaging) was found. CONCLUSIONS Most of the tools used to assess arthritis in SSc patients have not been validated and additional work is needed to develop a "core set" of variables for assessment of arthritis in SSc and its response to treatment. This report furnishes the background information that can help provide the building blocks for the development of a "core set" that can be used to chart the efficacy of new treatments for SSc-related arthritis in the future.
Collapse
Affiliation(s)
- Philip J Clements
- David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1670, USA.
| | | | | | | | | |
Collapse
|
|
47
|
Polido-Pereira J, Rodrigues AM, Canhão H, Saraiva F, da Silva JAP, Fonseca JE. Primary biliary cirrhosis in a rheumatoid arthritis patient treated with rituximab, a case-based review. Clin Rheumatol 2011; 31:385-9. [PMID: 22042492 DOI: 10.1007/s10067-011-1879-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2011] [Revised: 09/26/2011] [Accepted: 10/12/2011] [Indexed: 12/30/2022]
Abstract
Primary biliary cirrhosis (PBC) is an autoimmune disease in which intrahepatic bile ducts are targeted by an immune-mediated injury. This disease tends to progress to fibrosis and cirrhosis with hepatic failure. The authors report a case of a 50-year-old rheumatoid arthritis (RA) patient, with erosions and seropositive for rheumatoid factor and anti-citrullinated peptide antibodies, with 18 years disease duration refractory to prednisolone and several disease-modifying antirheumatic drugs, either conventional or biological (adalimumab and etanercept). In April 2007, she started therapy with rituximab (RTX) with good European League Against Rheumatism response achieved 9 months later. In June 2008, she was admitted with intrahepatic cholestasis, steatorrhea, and spontaneous fractures of various ribs. After excluding cholelitiasis, as well as infectious and neoplastic diseases a liver biopsy was performed that was compatible with the diagnosis of PBC. The antinuclear antibodies (1/160) were positive as well as the antimitochondrial antibodies (1/640). Other antibodies were negative such as anti-SSA and anti-SSB. Afterwards, the patient started ursodesoxycholic acid 15 mg kg(-1) day(-1) with progressive improvement of cholestatic markers. A labial salivary gland biopsy was performed and showed findings compatible with the concomitant diagnosis of Sjögren's syndrome. Based on this clinical report, a detailed review of the clinical aspects of PBC is presented as well as its association with other immune-mediated inflammatory diseases, particularly, with RA.
Collapse
Affiliation(s)
- Joaquim Polido-Pereira
- Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
| | | | | | | | | | | |
Collapse
|
|
48
|
Taylor P, Gartemann J, Hsieh J, Creeden J. A systematic review of serum biomarkers anti-cyclic citrullinated Peptide and rheumatoid factor as tests for rheumatoid arthritis. Autoimmune Dis 2011; 2011:815038. [PMID: 21915375 PMCID: PMC3170888 DOI: 10.4061/2011/815038] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2010] [Revised: 04/19/2011] [Accepted: 05/10/2011] [Indexed: 12/16/2022] Open
Abstract
This systematic review assesses the current status of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) tests in the diagnosis and prognosis of rheumatoid arthritis (RA). We reviewed publications on tests and biomarkers for early diagnosis of RA from English-language MEDLINE-indexed journals and non-MEDLINE-indexed sources. 85 publications were identified and reviewed, including 68 studies from MEDLINE and 17 non-MEDLINE sources. Anti-CCP2 assays provide improved sensitivity over anti-CCP assays and RF, but anti-CCP2 and RF assays in combination demonstrate a positive predictive value (PPV) nearing 100%, greater than the PPV of either of the tests alone. The combination also appears to be able to distinguish between patients whose disease course is expected to be more severe and both tests are incorporated in the 2010 ACR Rheumatoid Arthritis Classification Criteria. While the clinical value of anti-CCP tests has been established, differences in cut-off values, sensitivities and specificities exist between first-, second- and third-generation tests and harmonization efforts are under way. Anti-CCP and RF are clinically valuable biomarkers for the diagnosis and prognosis of RA patients. The combination of the two biomarkers in conjunction with other clinical measures is an important tool for the diagnosis and management of RA patients.
Collapse
Affiliation(s)
- Peter Taylor
- Kennedy Institute of Rheumatology Division, Imperial College, London W6 8LH, UK
| | | | - Jeanie Hsieh
- Roche Diagnostics, Ltd., Forrenstraβe, 6343 Rotkreuz, Switzerland
| | - James Creeden
- Roche Diagnostics, Ltd., Forrenstraβe, 6343 Rotkreuz, Switzerland
| |
Collapse
|
|
49
|
IgG RF and anti-CCP2 antibody can be positive in undifferentiated arthritis due to streptococcal infection, hepatitis B virus, tuberculosis, trauma and hypothyroidism: a preliminary study. Rheumatol Int 2011; 32:2687-90. [PMID: 21789619 DOI: 10.1007/s00296-011-1985-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2010] [Accepted: 07/03/2011] [Indexed: 10/18/2022]
Abstract
Anti-CCP2 antibody and rheumatoid (RF) tests are used for the diagnosis of rheumatoid arthritis (RA). Out of these two, anti-CCP2 antibody is supposed to be more specific for RA. Aim of the study was to present 33 cases of undifferentiated arthritis (UA) in which features of RA were not present, but anti-CCP2 antibody was positive. Out of the 33 cases of UA, 19 had well-known disease like hyperthyroidism, hypothyroidism, tubercular arthritis, traumatic arthritis, pneumonia with arthritis, varicose vein with pain in legs, cervical spondylitis and SSA. The duration of disease was more than one year in 67.86% cases. Majority of the patients were females (63.64%). Knee joint involvement was seen in maximum number (i.e. 20 cases). All 33 cases were positive for anti-CCP2 Ab. Maximum number of cases (78.78%) had involvement of one or two joints. CRP positivity was seen in 23.07% cases. Morning stiffness was present in (36.36%) cases, while swelling of the joint was present in 33.33% cases. In 16 cases, only serum sample was available for further analysis. About 62.5% cases showed IgG RF positivity. Antitubercular IgM and IgG were detected in 18.75% cases; ASO was elevated in 12.5% cases, and HBs Ag was positive in 6.25% cases. None of the controls (30 cases) were positive for these infections, anti-CCP2 antibody or RF. Thus, our study concludes that chronic infections like streptococcus, hepatitis B, tuberculosis and autoimmune thyroid diseases can produce raised levels of anti-CCP2 antibody and IgG RF.
Collapse
|
|
50
|
Abstract
Primary biliary cirrhosis (PBC) is a chronic, progressive, cholestatic, organ-specific autoimmune disease of unknown etiology. It predominantly affects middle-aged women, and is characterized by autoimmune-mediated destruction of small- and medium-size intrahepatic bile ducts, portal inflammation and progressive scarring, which without proper treatment can ultimately lead to fibrosis and hepatic failure. Serum autoantibodies are crucial tools for differential diagnosis of PBC. While it is currently accepted that antimitochondrial antibodies are the most important serological markers of PBC, during the last five decades more than sixty autoantibodies have been explored in these patients, some of which had previously been thought to be specific for other autoimmune diseases.
Collapse
|