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Rigopoulou EI, Lygoura V, Gabeta S, Gatselis N, Giannoulis G, Dalekos GN. Increased IgG Levels at Diagnosis Are Associated With Worse Prognosis of Patients With Primary Biliary Cholangitis. Liver Int 2025; 45:e70074. [PMID: 40125888 DOI: 10.1111/liv.70074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 02/09/2025] [Accepted: 03/17/2025] [Indexed: 03/25/2025]
Abstract
BACKGROUND AND AIM A proportion of patients with primary biliary cholangitis (PBC) have increased IgG (I-IgG) levels at baseline, though not fulfilling the criteria of autoimmune hepatitis/PBC variant. Our aim was to evaluate whether I-IgG has prognostic significance in non-cirrhotic PBC patients. METHODS Retrospective analysis of prospectively collected data from 675 PBC patients (592 non-cirrhotic) with available IgG levels at first evaluation was performed. RESULTS Among non-cirrhotic patients, 97 with I-IgG were more frequently females (p < 0.05), having a higher frequency of concurrent autoimmune diseases (p = 0.01) and a higher frequency of PBC-specific ANA (p < 0.001), sp100 (p < 0.001) and gp210 (p = 0.029) compared to 495 with normal IgG (N-IgG). Patients with I-IgG were older (p < 0.001) and had lower albumin (p < 0.001) and higher AST (p < 0.001), ALT (p = 0.005), ALP (p = 0.006), γGT (p = 0.038) and IgM (p < 0.001) compared to those with N-IgG. I-IgG patients had a higher probability of cirrhosis development (Breslow p < 0.001; log-rank p = 0.05) and liver-related death (Breslow p = 0.034; log-rank p < 0.05) compared to N-IgG patients. IgG > 1.5xULN was the highest risk factor for cirrhosis development (HR = 9.507, 95% CI: 1.221-74.038, p = 0.032) and liver-related death (HR = 27.140, 95% CI: 3.111-236.783; p = 0.003); IgG normalisation after 1 year of UDCA treatment had a favourable effect on disease outcome. Ν-IgG was associated with a higher probability of liver stiffness regression (p = 0.025). CONCLUSIONS This long-term study demonstrates that I-IgG levels characterise a subgroup of non-cirrhotic PBC patients with faster disease progression and increased probability of liver-related death. Normalisation of IgG levels during UDCA treatment seems to improve prognosis and therefore, these patients could benefit from stricter follow-up and earlier add-on second-line treatments.
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Affiliation(s)
- Eirini I Rigopoulou
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece
| | - Vassiliki Lygoura
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece
| | - Stella Gabeta
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece
| | - Nikolaos Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece
| | - George Giannoulis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece
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I. Rigopoulou E, Bakarozi M, Dimas I, Galanis K, Lygoura V, K. Gatselis N, Koulentaki M, N. Dalekos G. Total and individual PBC-40 scores are reliable for the assessment of health-related quality of life in Greek patients with primary biliary cholangitis. J Transl Int Med 2023; 11:246-254. [PMID: 37818155 PMCID: PMC10561069 DOI: 10.2478/jtim-2023-0098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/12/2023] Open
Abstract
Background Primary biliary cholangitis (PBC) has been long associated with impairment of various aspects of health-related quality of life (HRQoL) with substantial differences among populations. This study evaluated for the first-time the HRQoL in Greek PBC patients in conjunction with clinical and laboratory parameters of patients. Methods We analyzed prospectively collected data regarding the HRQoL by using the PBC-40 and SF-36 questionnaires in 374 Greek PBC patients and 131 age- and sex-matched non-PBC controls. Results The PBC-40 questionnaire is a reliable tool for HRQoL assessment in Greek PBC patients (Cronbach's α > 0.7 for all domains). Implementation of PBC-40 and SF-36 demonstrated significant impairment of HRQoL in Greek PBC patients compared to controls (P < 0.001 for all comparisons). Emotional dysfunction, social impairment, and fatigue (100%, 80.5% and 78%, respectively) were amongst those with the highest, while cognitive dysfunction (32%) with the least impact on quality of life. Fatigue was associated with female sex (P = 0.02), longer disease duration (P = 0.01), presence of cirrhosis (P = 0.02) and positivity for PBC-specific ANA (P < 0.05), while social dysfunction with increased age (P < 0.001), longer disease duration (P < 0.001) and presence of cirrhosis (P = 0.004). Living in urban areas was linked to impaired social function (P = 0.04), cognition (P = 0.02), fatigue (P = 0.04) and increased total PBC-40 score (P = 0.01). Conclusions Implementation of PBC-40 and SF-36 revealed impaired HRQoL in Greek PBC patients with fatigue, social and emotional dysfunction exerting the highest impact. However, total, and individual PBC-40 scores were lower than that reported in studies from Northern/Central Europe and Canada. Deranged HRQoL was associated with severity of liver disease and presence of PBC-specific ANA.
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Affiliation(s)
- Eirini I. Rigopoulou
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa41110, Greece
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa41110, Greece
| | - Marianna Bakarozi
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa41110, Greece
| | - Ioannis Dimas
- Hepatology Outpatient Clinic, Gastroenterology Department, University Hospital Heraklion, Heraklion, Crete 70013, Greece
| | - Konstantinos Galanis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa41110, Greece
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa41110, Greece
| | - Vasiliki Lygoura
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa41110, Greece
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa41110, Greece
| | - Nikolaos K. Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa41110, Greece
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa41110, Greece
| | - Mairi Koulentaki
- Hepatology Outpatient Clinic, Gastroenterology Department, University Hospital Heraklion, Heraklion, Crete 70013, Greece
| | - George N. Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa41110, Greece
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa41110, Greece
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Rigopoulou EI, Bogdanos DP. Role of autoantibodies in the clinical management of primary biliary cholangitis. World J Gastroenterol 2023; 29:1795-1810. [PMID: 37032725 PMCID: PMC10080701 DOI: 10.3748/wjg.v29.i12.1795] [Citation(s) in RCA: 8] [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: 12/05/2022] [Revised: 01/04/2023] [Accepted: 03/14/2023] [Indexed: 03/28/2023] Open
Abstract
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by immune-driven destruction of small intrahepatic bile ducts leading a proportion of patients to hepatic failure over the years. Diagnosis at early stages in concert with ursodeoxycholic acid treatment has been linked with prevention of disease progression in the majority of cases. Diagnosis of PBC in a patient with cholestasis relies on the detection of disease-specific autoantibodies, including anti-mitochondrial antibodies, and disease-specific anti-nuclear antibodies targeting sp100 and gp210. These autoantibodies assist the diagnosis of the disease, and are amongst few autoantibodies the presence of which is included in the diagnostic criteria of the disease. They have also become important tools evaluating disease prognosis. Herein, we summarize existing data on detection of PBC-related autoantibodies and their clinical significance. Moreover, we provide insight on novel autoantibodies and their possible prognostic role in PBC patients.
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Affiliation(s)
- Eirini I Rigopoulou
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa 41110, Greece
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa 41110, Greece
| | - Dimitrios P Bogdanos
- Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa 41110, Greece
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Gaiani F, Minerba R, Picanza A, Russo A, Melegari A, De Santis E, Trenti T, Belloni L, Peveri S, Aloe R, Ferrari C, Laghi L, de’Angelis GL, Bonaguri C. Optimization of Laboratory Diagnostics of Primary Biliary Cholangitis: When Solid-Phase Assays and Immunofluorescence Combine. J Clin Med 2022; 11:5238. [PMID: 36079166 PMCID: PMC9457280 DOI: 10.3390/jcm11175238] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 08/31/2022] [Accepted: 09/02/2022] [Indexed: 11/23/2022] Open
Abstract
The laboratory diagnostics of primary biliary cholangitis (PBC) have substantially improved, thanks to innovative analytical opportunities, such as enzyme-linked immunosorbent assays (ELISA) and multiple immunodot liver profile tests, based on recombinant or purified antigens. This study aimed to identify the best diagnostic test combination to optimize PBC diagnosis. Between January 2014 and March 2017, 164 PBC patients were recruited at the hospitals of Parma, Modena, Reggio-Emilia, and Piacenza. Antinuclear antibodies (ANA) and anti-mitochondrial antibodies (AMA) were assayed by indirect immunofluorescence (IIF), ELISA, and immunodot assays (PBC Screen, MIT3, M2, gp210, and sp100). AMA-IIF resulted in 89.6% positive cases. Using multiple immunodot liver profiles, AMA-M2 sensitivity was 94.5%, while anti-gp210 and anti-sp100 antibodies were positive in 16.5% and 17.7% of patients, respectively. PBC screening yielded positive results in 94.5% of cases; MIT3, sp100, and gp210 were detected by individual ELISA test in 89.0%, 17.1%, and 18.9% of patients, respectively. The association of PBC screening with IIF-AMA improved the diagnostic sensitivity from 89.6% to 98.2% (p < 0.01). When multiple immunodot liver profile testing was integrated with AMA-IIF, the diagnostic sensitivity increased from 89.1% to 98.8% (p < 0.01). The combination of IIF with solid-phase methods significantly improved diagnostic efficacy in PBC patients.
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Affiliation(s)
- Federica Gaiani
- Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy
- Gastroenterology and Endoscopy Unit, University Hospital of Parma, Via Gramsci 14, 43126 Parma, Italy
| | - Roberta Minerba
- Laboratory of Clinical Chemistry and Hematology, University Hospital of Parma, Via Gramsci 14, 43126 Parma, Italy
| | - Alessandra Picanza
- Laboratory of Clinical Chemistry and Hematology, University Hospital of Parma, Via Gramsci 14, 43126 Parma, Italy
| | - Annalisa Russo
- Laboratory of Clinical Chemistry and Hematology, University Hospital of Parma, Via Gramsci 14, 43126 Parma, Italy
| | - Alessandra Melegari
- Autoimmunity Unit, Department of Laboratory Medicine and Pathology, S. Agostino Estense Hospital, Via Giardini 1355, 41126 Baggiovara, Italy
| | - Elena De Santis
- Autoimmunity Unit, Department of Laboratory Medicine and Pathology, S. Agostino Estense Hospital, Via Giardini 1355, 41126 Baggiovara, Italy
| | - Tommaso Trenti
- Department of Laboratory Medicine and Pathology, S. Agostino Estense Hospital, Via Giardini 1355, 41126 Baggiovara, Italy
| | - Lucia Belloni
- Unit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria Locale—IRCCS of Reggio-Emilia, Viale Risorgimento 80, 42123 Reggio-Emilia, Italy
| | - Silvia Peveri
- Allergology Unit, Guglielmo da Saliceto Hospital, Via Giuseppe Taverna 49, 29121 Piacenza, Italy
| | - Rosalia Aloe
- Laboratory of Clinical Chemistry and Hematology, University Hospital of Parma, Via Gramsci 14, 43126 Parma, Italy
| | - Carlo Ferrari
- Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy
- Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, University Hospital of Parma, Via Gramsci 14, 43126 Parma, Italy
| | - Luigi Laghi
- Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy
- Gastroenterology and Endoscopy Unit, University Hospital of Parma, Via Gramsci 14, 43126 Parma, Italy
| | - Gian Luigi de’Angelis
- Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy
- Gastroenterology and Endoscopy Unit, University Hospital of Parma, Via Gramsci 14, 43126 Parma, Italy
| | - Chiara Bonaguri
- Laboratory of Clinical Chemistry and Hematology, University Hospital of Parma, Via Gramsci 14, 43126 Parma, Italy
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Bonaguri C, Melegari A, Picanza A, Russo A, De Santis E, Trenti T, Parmeggiani M, Belloni L, Savi E, de'Angelis GL, Gaiani F, Ferrari C, Lippi G. Association of solid-phase assays to the indirect immunofluorescence in primary biliary cholangitis diagnosis: Results of an Italian multicenter study. Autoimmun Rev 2019; 18:102389. [PMID: 31520799 DOI: 10.1016/j.autrev.2019.102389] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 06/09/2019] [Indexed: 12/11/2022]
Affiliation(s)
- Chiara Bonaguri
- Laboratory of Clinical Chemistry and Hematology, University Hospital of Parma, Parma, Italy.
| | - Alessandra Melegari
- Department of Laboratory Medicine and Pathology, S.Agostino Estense Hospital, Modena, Italy
| | - Alessandra Picanza
- Laboratory of Clinical Chemistry and Hematology, University Hospital of Parma, Parma, Italy
| | - Annalisa Russo
- Laboratory of Clinical Chemistry and Hematology, University Hospital of Parma, Parma, Italy
| | - Elena De Santis
- Department of Laboratory Medicine and Pathology, S.Agostino Estense Hospital, Modena, Italy
| | - Tommaso Trenti
- Department of Laboratory Medicine and Pathology, S.Agostino Estense Hospital, Modena, Italy
| | - Maria Parmeggiani
- Unit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria, Locale, IRCCS of Reggio-Emilia, Reggio-Emilia, Italy
| | - Lucia Belloni
- Unit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria, Locale, IRCCS of Reggio-Emilia, Reggio-Emilia, Italy
| | - Eleonora Savi
- Allergy Unit, Guglielmo da Saliceto Hospital, Piacenza, Italy
| | | | - Federica Gaiani
- Gastroenterology and Endoscopy Unit, University Hospital of Parma, Parma, Italy
| | - Carlo Ferrari
- Unit of Infectious Diseases and Hepatology, University Hospital of Parma, Parma, Italy
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, University of Verona, Verona, Italy
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Dalekos GN, Gatselis NK. Variant and Specific Forms of Autoimmune Cholestatic Liver Diseases. Arch Immunol Ther Exp (Warsz) 2019; 67:197-211. [PMID: 31165900 DOI: 10.1007/s00005-019-00550-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Accepted: 05/31/2019] [Indexed: 12/12/2022]
Abstract
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the main autoimmune cholestatic liver diseases. IgG4-associated sclerosing cholangitis is another distinct immune-mediated cholestatic disorder of unknown aetiology that is frequently associated with autoimmune pancreatitis or other IgG4-related diseases. Although the majority of PBC and PSC patients have a typical presentation, there are common and uncommon important variants or specific subgroups that observed in everyday routine clinical practice. In this updated review, we summarize the published data giving also our own experience on the variants and specific groups of autoimmune cholestatic liver diseases. Actually, we give in detail the underlining difficulties and the rising dilemmas concerning the diagnosis and management of these special conditions in the clinical spectrum of autoimmune cholestatic liver diseases including the IgG4-associated sclerosing cholangitis highlighting also the uncertainties and the potential new eras of the research agenda.
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Affiliation(s)
- George N Dalekos
- Institute of Internal Medicine and Hepatology, Larissa, Greece.
- Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, 41110, Larissa, Greece.
| | - Nikolaos K Gatselis
- Institute of Internal Medicine and Hepatology, Larissa, Greece
- Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, 41110, Larissa, Greece
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Polychronopoulou E, Lygoura V, Gatselis NK, Dalekos GN. Increased cholestatic enzymes in two patients with long-term history of ulcerative colitis: consider primary biliary cholangitis not always primary sclerosing cholangitis. BMJ Case Rep 2017; 2017:bcr-2017-220824. [PMID: 28951510 DOI: 10.1136/bcr-2017-220824] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Several hepatobiliary disorders have been reported in ulcerative colitis (UC) patients with primary sclerosing cholangitis (PSC) being the most specific. Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, rarely occurs in UC. We present two PBC cases of 67 and 71 years who suffered from long-standing UC. Both patients were asymptomatic but they had increased cholestatic enzymes and high titres of antimitochondrial antibodies (AMA)-the laboratory hallmark of PBC. After careful exclusion of other causes of cholestasis by MRI/magnetic resonance cholangiopancreatography (MRCP), virological and microbiological investigations, a diagnosis of PBC associated with UC was established. The patients started ursodeoxycholic acid (13 mg/kg/day) with complete response. During follow-up, both patients remained asymptomatic with normal blood biochemistry. Although PSC is the most common hepatobiliary manifestation among patients with UC, physicians must keep also PBC in mind in those with unexplained cholestasis and repeatedly normal MRCP. In these cases, a reliable AMA testing can help for an accurate diagnosis.
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Affiliation(s)
- Erietta Polychronopoulou
- Department of Medicine and Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece
| | - Vasiliki Lygoura
- Department of Medicine and Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece
| | - Nikolaos K Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece
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8
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Gatselis NK, Dalekos GN. Molecular diagnostic testing for primary biliary cholangitis. Expert Rev Mol Diagn 2016; 16:1001-10. [DOI: 10.1080/14737159.2016.1217159] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Nikolaos K. Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece
| | - George N. Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece
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Lyberopoulou A, Chachami G, Gatselis NK, Kyratzopoulou E, Saitis A, Gabeta S, Eliades P, Paraskeva E, Zachou K, Koukoulis GK, Mamalaki A, Dalekos GN, Simos G. Low Serum Hepcidin in Patients with Autoimmune Liver Diseases. PLoS One 2015; 10:e0135486. [PMID: 26270641 PMCID: PMC4535884 DOI: 10.1371/journal.pone.0135486] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2015] [Accepted: 07/22/2015] [Indexed: 12/15/2022] Open
Abstract
Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21), HBV (n = 23), autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34), autoimmune hepatitis (AIH; n = 16) and non-alcoholic fatty liver disease (NAFLD; n = 32). Sera sampled on the biopsy day from the same patients were investigated for serum hepcidin levels. Hepatic hepcidin mRNA levels correlated positively with ferritin and negatively with serum γ-GT levels. However, no correlation was found between serum hepcidin and either ferritin or liver hepcidin mRNA. Both serum hepcidin and the serum hepcidin/ferritin ratio were significantly lower in AIH and PBC/PSC patients’ sera compared to HBV, HCV or NAFLD (P<0.001 for each comparison) and correlated negatively with serum ALP levels. PBC/PSC and AIH patients maintained low serum hepcidin during the course of their two-year long treatment. In summary, parallel determination of liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases shows that circulating hepcidin and its respective ratio to ferritin are significantly diminished in patients with autoimmune liver diseases. These novel findings, once confirmed by follow-up studies involving bigger size and better-matched disease subgroups, should be taken into consideration during diagnosis and treatment of autoimmune liver diseases.
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MESH Headings
- Adult
- Aged
- Cholangitis, Sclerosing/blood
- Cholangitis, Sclerosing/genetics
- Cholangitis, Sclerosing/pathology
- Diagnosis, Differential
- Down-Regulation
- Female
- Ferritins/blood
- Hepatitis B/blood
- Hepatitis B/genetics
- Hepatitis B/pathology
- Hepatitis C/blood
- Hepatitis C/genetics
- Hepatitis C/pathology
- Hepatitis, Autoimmune/blood
- Hepatitis, Autoimmune/genetics
- Hepatitis, Autoimmune/pathology
- Hepcidins/blood
- Hepcidins/genetics
- Humans
- Liver/metabolism
- Liver/pathology
- Liver Cirrhosis, Biliary/blood
- Liver Cirrhosis, Biliary/genetics
- Liver Cirrhosis, Biliary/pathology
- Male
- Middle Aged
- Non-alcoholic Fatty Liver Disease/blood
- Non-alcoholic Fatty Liver Disease/genetics
- Non-alcoholic Fatty Liver Disease/pathology
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Affiliation(s)
- Aggeliki Lyberopoulou
- Laboratory of Biochemistry, Faculty of Medicine, University of Thessaly, Larissa, Greece
- Institute for Research & Technology—Thessaly (IRETETH), Larissa, Greece
| | - Georgia Chachami
- Laboratory of Biochemistry, Faculty of Medicine, University of Thessaly, Larissa, Greece
- Institute for Research & Technology—Thessaly (IRETETH), Larissa, Greece
| | - Nikolaos K. Gatselis
- Department of Medicine & Research Laboratory of Internal Medicine, Faculty of Medicine, University of Thessaly, Larissa, Greece
| | - Eleni Kyratzopoulou
- Laboratory of Molecular Biology and Immunobiotechnology, Hellenic Pasteur Institute, Athens, Greece
| | - Asterios Saitis
- Department of Medicine & Research Laboratory of Internal Medicine, Faculty of Medicine, University of Thessaly, Larissa, Greece
| | - Stella Gabeta
- Department of Medicine & Research Laboratory of Internal Medicine, Faculty of Medicine, University of Thessaly, Larissa, Greece
| | - Petros Eliades
- Laboratory of Molecular Biology and Immunobiotechnology, Hellenic Pasteur Institute, Athens, Greece
| | - Efrosini Paraskeva
- Laboratory of Physiology, Faculty of Medicine, University of Thessaly, Larissa, Greece
| | - Kalliopi Zachou
- Department of Medicine & Research Laboratory of Internal Medicine, Faculty of Medicine, University of Thessaly, Larissa, Greece
| | - George K. Koukoulis
- Department of Pathology, Faculty of Medicine, University of Thessaly, Larissa, Greece
| | - Avgi Mamalaki
- Laboratory of Molecular Biology and Immunobiotechnology, Hellenic Pasteur Institute, Athens, Greece
| | - George N. Dalekos
- Department of Medicine & Research Laboratory of Internal Medicine, Faculty of Medicine, University of Thessaly, Larissa, Greece
- * E-mail: (GS); (GND)
| | - George Simos
- Laboratory of Biochemistry, Faculty of Medicine, University of Thessaly, Larissa, Greece
- Institute for Research & Technology—Thessaly (IRETETH), Larissa, Greece
- * E-mail: (GS); (GND)
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Norman GL, Yang CY, Ostendorff HP, Shums Z, Lim MJ, Wang J, Awad A, Hirschfield GM, Milkiewicz P, Bloch DB, Rothschild KJ, Bowlus CL, Adamopoulos IE, Leung PS, Janssen HJ, Cheung AC, Coltescu C, Gershwin ME. Anti-kelch-like 12 and anti-hexokinase 1: novel autoantibodies in primary biliary cirrhosis. Liver Int 2015; 35:642-51. [PMID: 25243383 PMCID: PMC4305042 DOI: 10.1111/liv.12690] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2014] [Accepted: 09/15/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Using high-density human recombinant protein microarrays, we identified two potential biomarkers, kelch-like 12 (KLHL12) and hexokinase-1 (HK1), in primary biliary cirrhosis (PBC). The objective of this study was to determine the diagnostic value of anti-KLHL12/HK1 autoantibodies in PBC. Initial discovery used sera from 22 patients with PBC and 62 non-PBC controls. KLHL12 and HK1 proteins were then analysed for immunoglobulin reactivity by immunoblot and enzyme-linked immunosorbent assay (ELISA) in two independent cohorts of PBC and disease/healthy control patients. METHODS Serum samples from 100 patients with PBC and 165 non-PBC disease controls were analysed by immunoblot and samples from 366 patients with PBC, 174 disease controls, and 80 healthy donors were tested by ELISA. RESULTS Anti-KLHL12 and anti-HK1 antibodies were each detected more frequently in PBC compared with non-PBC disease controls (P < 0.001). Not only are both markers highly specific for PBC (≥95%) but they also yielded higher sensitivity than anti-gp210 and anti-sp100 antibodies. Combining anti-HK1 and anti-KLHL12 with available markers (MIT3, gp210 and sp100), increased the diagnostic sensitivity for PBC. Most importantly, anti-KLHL12 and anti-HK1 antibodies were present in 10-35% of anti-mitochondrial antibody (AMA)-negative PBC patients and adding these two biomarkers to conventional PBC assays dramatically improved the serological sensitivity in AMA-negative PBC from 55% to 75% in immunoblot and 48.3% to 68.5% in ELISA. CONCLUSIONS The addition of tests for highly specific anti-KLHL12 and anti-HK1 antibodies to AMA and ANA serological assays significantly improves efficacy in the clinical detection and diagnosis of PBC, especially for AMA-negative subjects.
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Affiliation(s)
| | - Chen-Yen Yang
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA
| | | | | | | | - Jinjun Wang
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA
| | | | - Gideon M. Hirschfield
- Centre for Liver Research, Institute of Biomedical Research, University of Birmingham, UK
| | - Piotr Milkiewicz
- Department of General, Transplant and Liver Surgery, Warsaw Medical University, Poland
| | - Donald B. Bloch
- The Center for Immunology and Inflammatory Diseases and the Division of Rheumatology, Allergy and Immunology of the General Medical Services and the Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Harvard, MA, USA
| | | | - Christopher L. Bowlus
- Division of Gastroenterology and Hepatology, University of California, Davis, CA, USA
| | - Iannis E. Adamopoulos
- Institute of Pediatric and Regenerative Medicine, Shriners Hospital for Northern California, Sacramento, CA, USA
| | - Patrick S.C. Leung
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA
| | - Harry J. Janssen
- Division of Gastroenterology, University of Toronto, Ontario, Canada,Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Netherlands
| | - Angela C. Cheung
- Division of Gastroenterology, University of Toronto, Ontario, Canada
| | - Catalina Coltescu
- Toronto Center for Liver Diseases, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
| | - M. Eric Gershwin
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA
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Gatselis NK, Zachou K, Koukoulis GK, Dalekos GN. Autoimmune hepatitis, one disease with many faces: Etiopathogenetic, clinico-laboratory and histological characteristics. World J Gastroenterol 2015; 21:60-83. [PMID: 25574080 PMCID: PMC4284362 DOI: 10.3748/wjg.v21.i1.60] [Citation(s) in RCA: 128] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Revised: 10/30/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
Autoimmune hepatitis (AIH) is an unresolving progressive liver disease of unknown etiology characterized by hypergammaglobulinemia, autoantibodies detection and interface hepatitis. Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical, laboratory and histological features, AIH diagnosis may be potentially difficult. Therefore, in this in-depth review we summarize the substantial progress on etiopathogenesis, clinical, serological and histological phenotypes of AIH. AIH has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis. Hypergammaglobulinemia with selective elevation of IgG is found in most cases. Autoimmune attack is perpetuated, possibly via molecular mimicry, and favored by the impaired control of T-regulatory cells. Histology (interface hepatitis, emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic, are still the hallmark for a timely diagnosis. AIH remains a major diagnostic challenge. AIH should be considered in every case in the absence of viral, metabolic, genetic and toxic etiology of chronic or acute hepatitis. Laboratory personnel, hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient.
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12
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Gatselis NK, Zachou K, Norman GL, Gabeta S, Papamichalis P, Koukoulis GK, Dalekos GN. Clinical significance of the fluctuation of primary biliary cirrhosis-related autoantibodies during the course of the disease. Autoimmunity 2013; 46:471-479. [PMID: 23777462 DOI: 10.3109/08916934.2013.801461] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Primary biliary cirrhosis (PBC) is a chronic cholestatic disease characterized by the presence of antimitochondrial antibodies (AMA). PBC-specific antinuclear antibodies (ANA) have been characterized and associated with disease progression and outcome. We evaluated the clinical significance of the presence and serial changes in titers of AMA, PBC-specific ANA (anti-gp210, anti-sp100) and anti-chromatin antibodies. Over a median (IQR) period of 35 (36) months, 512 specimens were collected from 110 patients. Autoantibodies were detected by commercial ELISAs (INOVA Diagnostics). Biochemical, clinical, and histological status were included at initial presentation and during follow-up visits. The Mayo risk score was calculated as a prognostic index at each time point. Liver biopsy findings were classified according to Ludwig's classification and biochemical response to ursodeoxycholic acid was evaluated according to Pares. At baseline, AMA IgG and IgA, anti-gp210 IgG, anti-sp100 IgG and anti-chromatin IgG were detected in 92/110 (83.6%), 57/110 (51.8%), 5/110 (4.5%), 14/110 (12.7%), and 0/110 (0%) patients, respectively. Positivity for all autoantibodies apart from anti-chromatin, at baseline visit (n = 110 patients), in all tested sera (n = 512) as well as increased autoantibodies titers during follow-up were associated with biochemically and/or histologically advanced disease. A decrease of anti-sp100 titers but not of anti-gp210 titers during follow-up was associated with improvement of Mayo risk score (p = 0.025) and response to ursodeoxycholic acid (p = 0.016). These results suggest that detection of AMA and PBC-specific ANA was correlated with disease severity. Serial changes of anti-sp100 titers and not of anti-gp210 titers might prove useful for monitoring the disease course and treatment outcome.
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Affiliation(s)
- Nikolaos K Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, Medical School, University of Thessaly , Larissa , Greece
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13
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Rigopoulou EI, Zachou K, Gatselis NK, Papadamou G, Koukoulis GK, Dalekos GN. Primary biliary cirrhosis in HBV and HCV patients: Clinical characteristics and outcome. World J Hepatol 2013; 5:577-583. [PMID: 24179617 PMCID: PMC3812460 DOI: 10.4254/wjh.v5.i10.577] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2013] [Revised: 09/03/2013] [Accepted: 10/16/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To present the characteristics, management and outcome of patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infections concurrent with primary biliary cirrhosis (PBC).
METHODS: Since January 2001 to September 2009, we retrospectively evaluated the medical records of all HBV (n = 1493) and HCV patients (n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC (8 HCV and PBC; follow-up: 61 ± 37 mo and 9 HBV and PBC; follow-up: 57 ± 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of PBC.
RESULTS: HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients, while one third (5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV (56.1 ± 11.2 vs 68.5 ± 10.3, respectively, P < 0.05). At initial clinical and histological assessment the majority of patients were cirrhotics (10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency (87.5% vs 33.3% in PBC and HBV; P < 0.05). The patients with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during follow-up.
CONCLUSION: PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC.
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14
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Zachou K, Muratori P, Koukoulis GK, Granito A, Gatselis N, Fabbri A, Dalekos GN, Muratori L. Review article: autoimmune hepatitis -- current management and challenges. Aliment Pharmacol Ther 2013; 38:887-913. [PMID: 24010812 DOI: 10.1111/apt.12470] [Citation(s) in RCA: 113] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2013] [Revised: 03/22/2013] [Accepted: 08/12/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is a disease of unknown aetiology characterised by interface hepatitis, hypergammaglobulinaemia, circulating autoantibodies and a favourable response to immunosuppression. AIM To review recent advancements in understanding aetiopathogenesis, clinical, serological and histological features, diagnostic criteria and treatment strategies of AIH. METHODS Published studies on AIH extracted mainly from PubMed during the last 15 years. RESULTS Autoimmune hepatitis has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations are variable ranging from no symptoms to severe acute hepatitis and only seldom to fulminant hepatic failure. Autoimmune attack is perpetuated, possibly via molecular mimicry mechanisms, and favoured by the impaired control of regulatory T-cells. A typical laboratory finding is hypergammaglobulinaemia with selective elevation of IgG, although in 15-25% of patients - particularly children, elderly and acute cases - IgG levels are normal. Liver histology and autoantibodies, although not pathognomonic, still remain the hallmark for diagnosis. Immunosuppressive treatment is mandatory and life-saving; however, to meet strict response criteria, the conventional therapy with prednisolone with or without azathioprine is far from ideal. CONCLUSIONS Autoimmune hepatitis remains a major diagnostic and therapeutic challenge. The clinician, the hepato-pathologist and the laboratory personnel need to become more familiar with different expressions of the disease, interpretation of liver histology and autoimmune serology. According to the strict definition of treatment response issued by the 2010 AASLD guidelines, many patients are nonresponders to conventional treatment. Newer immunosuppressive agents targeting pathogenetic mechanisms can improve patient management, which needs to be tailored on a case-by-case basis.
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Affiliation(s)
- K Zachou
- Department of Medicine and Research Laboratory of Internal Medicine, Medical School, Thessaly University, Larissa, Greece
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15
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Abstract
Antibodies play an important role in autoimmune liver diseases, such as autoimmune hepatitis (AIH). On the one hand, they are essential diagnostic markers to identify not only the presentation of AIH, but also the AIH subtype characterized by the presence of particular antibodies to target autoantigens in the liver. On the other hand, such autoantibodies might be directly involved in the etiology and/or pathogenesis of AIH. This review will reflect on the evidence of how specific autoantibodies influence AIH and will further provide insight into the necessities for generating therapeutic antibodies to treat AIH in the future.
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Affiliation(s)
- Urs Christen
- Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital Frankfurt, Theodor-Stern Kai 7, 60590 Frankfurt am Main, Germany
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16
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Achenza MIS, Meda F, Brunetta E, Selmi C. Serum autoantibodies for the diagnosis and management of autoimmune liver diseases. Expert Rev Gastroenterol Hepatol 2012; 6:717-29. [PMID: 23237257 DOI: 10.1586/egh.12.58] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The spectrum of autoimmune liver diseases (AILD) includes primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. The immunological mechanisms triggering the initiation and perpetuation of AILD remains unknown, while autoantigens are now recognized in most cases, and are generally nontraditional in their widespread distribution. Sensitive and specific methods for the detection of serum autoantibodies in patients affected by AILD represent a challenge for researchers and clinicians who desire to obtain an early and certain diagnosis as well as markers of disease control. To this regard, the use and interpretation of serum autoantibodies in AILD may be seen as paradigmatic for the large gaps in our knowledge based on the lack of true population-based studies. The present review article will critically discuss the available evidence on the use of autoantibody findings in the diagnosis or management of autoimmune liver disease.
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Affiliation(s)
- Maria I S Achenza
- Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
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17
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Zografos TA, Gatselis N, Zachou K, Liaskos C, Gabeta S, Koukoulis GK, Dalekos GN. Primary biliary cirrhosis-specific autoantibodies in first degree relatives of Greek primary biliary cirrhosis patients. World J Gastroenterol 2012; 18:4721-8. [PMID: 23002341 PMCID: PMC3442210 DOI: 10.3748/wjg.v18.i34.4721] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2012] [Revised: 03/31/2012] [Accepted: 04/09/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the prevalence and significance of primary biliary cirrhosis (PBC)-specific autoantibodies in first-degree relatives (FDRs) of Greek PBC patients.
METHODS: The presence of antimitochondrial antibodies (AMA) and PBC-specific antinuclear antibodies (ANA) were determined using indirect immunofluorescence assays, dot-blot assays, and molecularly based enzyme-linked immunosorbent assays in 101 asymptomatic for liver-related symptoms FDRs of 44 PBC patients. In order to specify our results, the same investigation was performed in 40 healthy controls and in a disease control group consisting of 40 asymptomatic for liver-related symptoms FDRs of patients with other autoimmune liver diseases namely, autoimmune hepatitis-1 or primary sclerosing cholangitis (AIH-1/PSC).
RESULTS: AMA positivity was observed in 19 (only 4 with abnormal liver function tests) FDRs of PBC patients and none of the healthy controls. The prevalence of AMA was significantly higher in FDRs of PBC patients than in AIH-1/PSC FDRs and healthy controls [18.8%, 95% confidence interval (CI): 12%-28.1% vs 2.5%, 95% CI: 0.1%-14.7%, P = 0.01; 18.8%, 95% CI: 12%-28.1% vs 0%, 95% CI: 0%-10.9%, P = 0.003, respectively]. PBC-specific ANA positivity was observed in only one FDR from a PSC patient. Multivariate analysis showed that having a proband with PBC independently associated with AMA positivity (odds ratio: 11.24, 95% CI: 1.27-25.34, P = 0.03) whereas among the investigated comorbidities and risk factors, a positive past history for urinary tract infections (UTI) was also independently associated with AMA detection in FDRs of PBC patients (odds ratio: 3.92, 95% CI: 1.25-12.35, P = 0.02).
CONCLUSION: In FDRs of Greek PBC patients, AMA prevalence is significantly increased and independently associated with past UTI. PBC-specific ANA were not detected in anyone of PBC FDRs.
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Granito A, Muratori P, Quarneti C, Pappas G, Cicola R, Muratori L. Antinuclear antibodies as ancillary markers in primary biliary cirrhosis. Expert Rev Mol Diagn 2012; 12:65-74. [PMID: 22133120 DOI: 10.1586/erm.11.82] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Antimitochondrial antibodies are the serological hallmark of primary biliary cirrhosis (PBC). Besides antimitochondrial antibodies, the autoantibody profile of PBC includes antinuclear antibodies (ANA) which are detectable by indirect immunofluorescence in up to 50% of PBC patients. Two immunofluorescence patterns are considered 'PBC-specific': the multiple nuclear dots and rim-like/membranous patterns. The target antigens of the multiple nuclear dots pattern have been identified as Sp100 and promyelocytic leukemia protein, whereas the rim-like/membranous pattern is given by autoantibodies recognizing multiple proteins such as gp210, nucleoporin p62 and the lamin B receptor. Other ANA, especially those already known in the rheumatological setting, such as anticentromere, anti-SSA/Ro and anti-dsDNA antibodies, can be frequently found in PBC, often coexisting in the same patient. In this article, we will report on recent progress in the antigenic characterization of ANA in PBC, their detection with both traditional assays and Western blot/ELISA with molecularly defined nuclear antigens, and we will discuss their clinical significance.
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Affiliation(s)
- Alessandro Granito
- Department of Clinical Medicine, Alma Mater Studiorum-University of Bologna, S.Orsola-Malpighi Hospital, Italy.
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Koumati E, Palassopoulou M, Matsouka P, Polyzos A, Dalekos GN, Zachou K. Multiple autoimmune propensity and B-non-hodgkin lymphoma: cause or effect? Autoimmune Dis 2011; 2011:841325. [PMID: 21687651 PMCID: PMC3112510 DOI: 10.4061/2011/841325] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2011] [Accepted: 03/01/2011] [Indexed: 11/24/2022] Open
Abstract
We report a case of multiple autoimmunity consisting of the presence of autoimmune haemolytic anaemia (AIHA), antimitochondrial antibodies (AMAs), and antiphospholipid antibodies (APLAbs) as the presenting manifestations of an extrahepatic B-non-Hodgkin lymphoma (B-NHL) in a 63-year-old woman. The patient presented with fatigue attributed to severe AIHA. Due to increased serum IgM and γ-GT levels, an investigation for AMA was performed, which proved positive with anti-M2 specificity. A prolongation of activated partial thromboplastin time (aPTT) led to the determination of APLAbs (lupus anticoagulant and other APLAbs) which were also positive. Bone marrow biopsy in combination with immmunohistochemical studies established the diagnosis of lymphoplasmacytic B-NHL. Ten months later, B-NHL was in remission while AMA and APLAbs were still positive. In conclusion, we documented the coexistence of multiple autoimmune reactions together with B-NHL highlighting the possible common pathogenetic pathways of the two entities.
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Affiliation(s)
- E Koumati
- Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Biopolis, Mezourlo, 41110 Larissa, Greece
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Early primary biliary cirrhosis: a new association with erythema nodosum of unknown origin. Gastroenterol Res Pract 2010; 2010. [PMID: 20706542 PMCID: PMC2913530 DOI: 10.1155/2010/121620] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2010] [Accepted: 06/22/2010] [Indexed: 12/14/2022] Open
Abstract
Primary biliary cirrhosis (PBC) is associated with immune-mediated dermatologic disorders. The association of PBC with erythema nodosum (EN) seems rare. We report two females (42 and 44 years old) with low-grade fever, arthralgias, and elevated cholestatic enzymes in the first and fatigue in the second. Patients were also suffering from typical EN lesions characterized by multiple erythematous, painful nodules over the anterior portions of their lower extremities. Clinical and extensive laboratory work up excluded all known EN causes. PBC diagnosis was established according to the cholestatic biochemical profile, anti-mitochondrial antibodies (AMA) positivity and liver histology (first), and AMA and antinuclear (ANA) PBC-specific antibodies (second). Our report may suggest that PBC could be kept in mind in EN patients of unknown aetiology and particularly, when middle-aged female patients are affected. In such cases a thorough evaluation for AMA and/or ANA PBC-specific antibodies could be helpful to achieve a correct and timely diagnosis.
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Prevalence of gastric parietal cell antibodies and intrinsic factor antibodies in primary biliary cirrhosis. Clin Chim Acta 2010; 411:411-5. [DOI: 10.1016/j.cca.2009.12.012] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2009] [Revised: 12/14/2009] [Accepted: 12/15/2009] [Indexed: 01/04/2023]
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