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Mihai IR, Rezus C, Burlui MA, Cardoneanu A, Macovei LA, Richter P, Bratoiu I, Rezus E. Autoimmune Liver Diseases and Rheumatoid Arthritis-Is There an Etiopathogenic Link? Int J Mol Sci 2024; 25:3848. [PMID: 38612658 PMCID: PMC11011907 DOI: 10.3390/ijms25073848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 02/28/2024] [Accepted: 03/23/2024] [Indexed: 04/14/2024] Open
Abstract
Rheumatoid arthritis (RA) is a systemic immune-mediated disease that, in addition to the articular involvement, can have extra-articular manifestations. Even though liver damage in RA is not very common, associated autoimmune liver diseases (AILDs) may occur. The most common AILD associated with RA is primary biliary cirrhosis (PBC), followed by autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). There are common underlying mechanisms that play a role in the emergence of autoimmunity and inflammation in both rheumatic and autoimmune liver diseases. Genetic studies have revealed the existence of several common disease-associated genes shared between RA and AILDs, and infectious triggers, particularly those associated with recurrent or complicated urinary tract infections, are also speculated to be potential triggers for these conditions. Moreover, these diseases share common serologic patterns characterized by the presence of specific autoantibodies and hyper-gammaglobulinemia. In this study, we focus on reviewing the association between RA and AILDs regarding the prevalence and possible etiopathogenic link.
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Affiliation(s)
- Ioana Ruxandra Mihai
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Ciprian Rezus
- Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- “Sfantul Spiridon” Emergency Hospital, 700111 Iasi, Romania
| | - Maria Alexandra Burlui
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Anca Cardoneanu
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Luana Andreea Macovei
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Patricia Richter
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Ioana Bratoiu
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Elena Rezus
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
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Faisal MS, Gonzalez HC, Gordon SC. Primary Biliary Cholangitis: Epidemiology, Diagnosis, and Presentation. Clin Liver Dis 2024; 28:63-77. [PMID: 37945163 DOI: 10.1016/j.cld.2023.06.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
Using ursodeoxycholic acid as a standard treatment and for its ability to test for antimitochondrial antibody to accelerate diagnosis, survival of primary biliary cholangitis patients has approached that of the general population, leading to a change in nomenclature from primary biliary cirrhosis to primary biliary cholangitis to more accurately describe the disease.
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Affiliation(s)
- Muhammad Salman Faisal
- Department of Gastroenterology and Hepatology, Henry Ford Health, 2799 West Grand Boulevard, Detroit, MI 48202, USA
| | - Humberto C Gonzalez
- Department of Gastroenterology and Hepatology, Henry Ford Health, 2799 West Grand Boulevard, Detroit, MI 48202, USA; Wayne State University School of Medicine, 540 East Canfield Street, Detroit, MI 48201, USA
| | - Stuart C Gordon
- Department of Gastroenterology and Hepatology, Henry Ford Health, 2799 West Grand Boulevard, Detroit, MI 48202, USA; Wayne State University School of Medicine, 540 East Canfield Street, Detroit, MI 48201, USA.
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Chen S, Li MQ, Duan WJ, Li BE, Li SX, Lv TT, Ma L, Jia JD. Concomitant extrahepatic autoimmune diseases do not compromise the long-term outcomes of primary biliary cholangitis. Hepatobiliary Pancreat Dis Int 2022; 21:577-582. [PMID: 35668014 DOI: 10.1016/j.hbpd.2022.05.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 05/19/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Primary biliary cholangitis (PBC) patients often have concomitant extrahepatic autoimmune (EHA) diseases including Sjögren's syndrome (SS), systemic sclerosis (SSc), rheumatoid arthritis (RA), and autoimmune thyroid disease. The present study aimed to describe the prevalence of EHA diseases in PBC and explore the impact of EHA diseases on the long-term outcomes of PBC in Chinese patients. METHODS Medical records of PBC patients diagnosed in our institute were retrospectively reviewed. Patients were followed up by a standardized telephone interview. The endpoints were defined as liver-related death and/or liver transplantation. RESULTS Totally 247 of the 985 (25.1%) PBC patients enrolled in the study had at least one concomitant EHA disease. Sjögren's syndrome (n = 140, 14.2%) was the most frequent one, followed by rheumatoid arthritis (RA) (n = 56, 5.7%) and Hashimoto's thyroiditis (n = 45, 4.6%). Patients with EHA diseases were more common in females (P < 0.001) and in those with a family history of autoimmune disease (P = 0.017). Overall, no differences were found between PBC patients with and without EHA diseases in terms of biochemical response rates to ursodeoxycholic acid, the incidence of hepatic events, or transplant-free survival. RA and EHA ≥ 2 were protective factors for hepatic events in univariate Cox analysis, but the results became insignificant in multivariate analysis. CONCLUSIONS Concomitant EHA diseases were common in PBC patients but did not compromise the long-term outcomes of PBC.
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Affiliation(s)
- Sha Chen
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, 95 Yong'an Road, Beijing 100050, China
| | - Meng-Qi Li
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, 95 Yong'an Road, Beijing 100050, China
| | - Wei-Jia Duan
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, 95 Yong'an Road, Beijing 100050, China
| | - Bu-Er Li
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, 95 Yong'an Road, Beijing 100050, China
| | - Shu-Xiang Li
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, 95 Yong'an Road, Beijing 100050, China
| | - Ting-Ting Lv
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, 95 Yong'an Road, Beijing 100050, China
| | - Lin Ma
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, 95 Yong'an Road, Beijing 100050, China
| | - Ji-Dong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, 95 Yong'an Road, Beijing 100050, China.
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Wang CR, Tsai HW. Autoimmune liver diseases in systemic rheumatic diseases. World J Gastroenterol 2022; 28:2527-2545. [PMID: 35949355 PMCID: PMC9254143 DOI: 10.3748/wjg.v28.i23.2527] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 03/11/2022] [Accepted: 05/14/2022] [Indexed: 02/06/2023] Open
Abstract
Systemic rheumatic diseases (SRDs) are chronic, inflammatory, autoimmune disorders with the presence of autoantibodies that may affect any organ or system. Liver dysfunction in SRDs can be associated with prescribed drugs, viral hepatitis, alternative hepatic comorbidities and coexisting autoimmune liver diseases (AILDs), requiring an exclusion of secondary conditions before considering liver involvement. The patterns of overlap diseases depend predominantly on genetic determinants with common susceptible loci widely distributing in both disorders. In AILDs, it is important to identify the overlapping SRDs at an early stage since such a coexistence may influence the disease course and prognosis. Commonly co-occurring SRDs in AILDs are Sjögren syndrome (SS), rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) in autoimmune hepatitis (AIH), and SS, RA or systemic sclerosis in primary biliary cholangitis. Owing to different disease complications and therapies, it is imperative to differentiate between SLE liver involvement and SLE-AIH overlap disease. Therapeutic options can be personalized to control coexisting conditions of liver autoimmunity and rheumatic manifestations in AILD-SRD overlap diseases. The collaboration between hepatologists and rheumatologists can lead to significant advances in managing such a complex scenario. In this review, we provide a comprehensive overview on coexisting AILDs in different SRDs and the therapeutic approach in managing these overlap diseases.
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Affiliation(s)
- Chrong-Reen Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan
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Xu J, Zhang H, Wang C, Jiang P, Han C, Dai Y, Qiu F, Gong Y, Jiang Y, Xu P, Zhang M, Zhang L, Shi X, Chen S, Tian Y, Seldin MF, Gershwin ME, Liu X, Li L. Increased sensitivity of gp210 autoantibody detection using a newly designed gp210 antigen. J Immunol Methods 2021; 501:113211. [PMID: 34971632 DOI: 10.1016/j.jim.2021.113211] [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: 07/23/2021] [Revised: 12/09/2021] [Accepted: 12/23/2021] [Indexed: 10/19/2022]
Abstract
OBJECTIVES The detection of autoantibody to glycoprotein 210 (gp210 Ab) against a 15 amino-acid peptide epitope by enzyme-linked immunosorbent assay (ELISA) has been widely used in the diagnosis of primary biliary cholangitis (PBC). However, this small peptide antigen presents spatial limitations for antibody access, which reduces the sensitivity of autoantibody detection. A recombinant gp210 antigen was constructed for increased sensitivity in antibody detection is described here. METHODS The gp210 C terminal 18 amino acid coding sequence was ligated to the modified C-terminal 108 amino acid coding sequence of human serum albumin (mHSA108) and produced as a recombinant gp210 antigen mHSA108-gp210-C18. Measurements of gp210 Ab using the gp210 C-terminal 25 amino acid peptide (gp210-C25) and mHSA108-gp210-C18 by in-house ELISA were compared. ELISAs with mHSA108-gp210-C18 and commercial INOVA kit for gp210 Ab detection were also compared in PBC patients and healthy controls. The correlation between the two assays was analyzed and their efficiency in diagnosing was compared. RESULTS Of 86 PBC samples, 35 (40.70%) and 44 (52.33%) positive samples were detected for anti-gp210 Ab using gp210-C25 and mHSA108-gp210-C18, respectively. Of 252 samples from PBC, 114 (45.24%) were positive for mHSA108-gp210-C18 ELISA whereas 94 (37.3%) for commercial ELISA (INOVA). All positive samples detected with commercial ELISA kit were also tested positive in mHSA108-gp210-C18 ELISA. Among 374 patients with other autoimmune diseases, anti-gp210 Ab were detected by mHSA108-gp210-C18 ELISA in 0.95% systemic lupus erythematosus (SLE) patients (2/210), 13.04% rheumatoid arthritis (RA) patients (13/97), and 1.47% of Sjögren's Syndrome (SS) patients (1/67). CONCLUSIONS Compared to the gp210 peptide antigen, the sensitivity of the ELISA system using mHSA108-gp210-C18 antigen was improved. The novel gp210 antigen could be useful for screening patients known to be at increased risk of developing PBC.
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Affiliation(s)
- Jing Xu
- Institute of Life Sciences and Technology, Southeast University, 2 Sipailou Road, Nanjing, Jiangsu 210096, China; Department of Clinical Laboratory, ZhongDa Hospital, Southeast University, Nanjing, Jiangsu 210009, China
| | - Haoyi Zhang
- Institute of Life Sciences and Technology, Southeast University, 2 Sipailou Road, Nanjing, Jiangsu 210096, China
| | - Chan Wang
- Institute of Translational Medicine, Medical College, Yangzhou University, 136 Yangjiang Middle Road, Yangzhou, Jiangsu 225001, China
| | - Peng Jiang
- Institute of Life Sciences and Technology, Southeast University, 2 Sipailou Road, Nanjing, Jiangsu 210096, China
| | - Chongxu Han
- Department of Laboratory Medicine, Subei People's Hospital, Clinical Medical College, Yangzhou University, 98 Nantong West Road, Yangzhou, Jiangsu 225001, China
| | - Yaping Dai
- Department of Laboratory Medicine, The Fifth People's Hospital of Wuxi, 1215 Guangrui Road, Wuxi, Jiangsu 214000, China
| | - Fang Qiu
- Department of Laboratory Medicine, The Forth Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210031, China
| | - Yuhua Gong
- Department of Laboratory Medicine, The Third People's Hospital of Zhenjiang, 300 Daijiamen, Zhenjiang, Jiangsu 212021, China
| | - Yuzhang Jiang
- Department of Laboratory Medicine, Huai'an First People's Hospital, Nanjing Medical University, 1 Huanghe West Road, Huai'an, Jiangsu 223300, China
| | - Ping Xu
- Department of Laboratory Medicine, The Fifth People's Hospital of Suzhou, Soochow University, 10 Guangqian Road, Suzhou, Jiangsu 215131, China
| | - Mingming Zhang
- Institute of Life Sciences and Technology, Southeast University, 2 Sipailou Road, Nanjing, Jiangsu 210096, China
| | - Luyao Zhang
- Institute of Life Sciences and Technology, Southeast University, 2 Sipailou Road, Nanjing, Jiangsu 210096, China
| | - Xingjuan Shi
- Institute of Life Sciences and Technology, Southeast University, 2 Sipailou Road, Nanjing, Jiangsu 210096, China
| | - Sufang Chen
- Department of Laboratory Medicine, The Fifth People's Hospital of Suzhou, Soochow University, 10 Guangqian Road, Suzhou, Jiangsu 215131, China
| | - Ye Tian
- Department of Radiology, The Second Affiliated Hospital of Soochow University，1055 Sanxiang Road, Suzhou, Jiangsu 215004, China
| | - Michael F Seldin
- Department of Biochemistry and Molecular Medicine, University of California at Davis School of Medicine, 4453 Tupper Hall, Davis, CA 95616, USA; Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, School of Medicine, Genome and Biomedical Sciences Facility Building, 451 Health Sciences Drive, Suite 6510, Davis, CA 95616, USA
| | - M Eric Gershwin
- Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, School of Medicine, Genome and Biomedical Sciences Facility Building, 451 Health Sciences Drive, Suite 6510, Davis, CA 95616, USA
| | - Xiangdong Liu
- Institute of Life Sciences and Technology, Southeast University, 2 Sipailou Road, Nanjing, Jiangsu 210096, China.
| | - Li Li
- Institute of Life Sciences and Technology, Southeast University, 2 Sipailou Road, Nanjing, Jiangsu 210096, China; Department of Clinical Laboratory, ZhongDa Hospital, Southeast University, Nanjing, Jiangsu 210009, China.
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Ahmed A, Kahlam A, Pai S, Ahlawat S. Clinical outcomes and resource utilization analysis in patients with rheumatoid arthritis undergoing endoscopic retrograde cholangiopancreatography. JGH Open 2021; 5:396-400. [PMID: 33732888 PMCID: PMC7936620 DOI: 10.1002/jgh3.12510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 02/03/2021] [Accepted: 02/08/2021] [Indexed: 11/19/2022]
Abstract
BACKGROUND AND AIM The literature is lacking on associations of endoscopic retrograde cholangiopancreatography (ERCP) related outcomes in rheumatoid arthritis (RA) patients. The aim of this study is to evaluate the effects of RA on clinical outcomes and hospital resource utilization in patients undergoing ERCP. METHODS The National Inpatient Sample database was used to identify hospitalized patients who had underwent an ERCP study from 2012 to 2014 using International Classification of Diseases-Ninth Edition (ICD-9) codes. Primary outcomes were mortality, hospital charges, and length of stay. Secondary outcomes were ERCP-related complications. Chi-squared tests for categorical data and independent t-test for continuous data were utilized. Multivariate analysis was performed to assess the primary outcomes. RESULTS There was 83 890 ERCP procedures performed, of which 970 patients had RA. In patients with RA, 74.2% were female, and the average age was 65.7 years. RA primary outcomes of mortality rate and hospital cost were lower and statistically significant. There was no statistically significant difference in secondary outcomes except for lower cholecystectomy rates in RA patients. CONCLUSION With a high inflammatory state, it was hypothesized that RA would be associated with worse outcomes after ERCP. Yet, the primary outcomes of mortality and hospital cost were found to be lower than controls, with no difference in secondary outcomes. We posit that immunosuppressants used to treat RA provides a protective effect to overall complications with ERCP.
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Affiliation(s)
- Ahmed Ahmed
- Department of MedicineRutgers New Jersey Medical SchoolNewarkNew JerseyUSA
| | - Aaron Kahlam
- Department of MedicineRutgers New Jersey Medical SchoolNewarkNew JerseyUSA
| | - Suraj Pai
- Department of MedicineRutgers New Jersey Medical SchoolNewarkNew JerseyUSA
| | - Sushil Ahlawat
- Department of Gastroenterology and HepatologyRutgers New Jersey Medical SchoolNewarkNew JerseyUSA
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Clinical connection between rheumatoid arthritis and liver damage. Rheumatol Int 2018; 38:715-724. [PMID: 29627896 DOI: 10.1007/s00296-018-4021-5] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2018] [Accepted: 03/26/2018] [Indexed: 12/15/2022]
Abstract
When liver damage is present in rheumatoid arthritis (RA) patients, it is sometimes difficult to determine whether it is a hepatic manifestation of RA, associated primary liver disease or hepatotoxic liver disease which developed during the treatment of RA. Liver damage during RA is most common in the form of asymptomatic abnormal liver tests. Occasionally, liver damage may progress to cirrhosis. Patients with RA are more susceptible to an associated autoimmune liver disease. Medications used in rheumatology are often hepatotoxic and it is difficult to differentiate between hepatic manifestations of the primary disease and potential hepatotoxicity of the administered medications. The significance of the paper is in the fact that it includes the most relevant and the latest information on this commonly present problem in clinical practice. The aim of the author is to provide comprehensive but at the same time concise data which will be useful to the doctors who come into contact with RA patients with symptomatic or asymptomatic liver disease. Timely diagnosis and treatment of liver disease in RA patients can significantly influence the course and outcome of rheumatoid arthritis.
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Ali AH, Carey EJ, Lindor KD. The management of autoimmunity in patients with cholestatic liver diseases. Expert Rev Gastroenterol Hepatol 2016; 10:73-91. [PMID: 26523975 DOI: 10.1586/17474124.2016.1095088] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Cholestatic liver diseases are rare diseases that often lead to cirrhosis and its consequent complications. In addition to liver-related morbidity, patients with cholestatic liver diseases often suffer from autoimmune diseases that affect several organs and tissues. The robust and efficient data collection and collaboration between hepatologists and rheumatologists have led to significant advancements in understanding the relationship between the cholestatic liver diseases and associated autoimmune diseases. In this paper, we discuss the cholestatic liver diseases (primary biliary cirrhosis, primary sclerosing cholangitis and immunoglobulin G4 associated cholangitis) and associated autoimmune diseases.
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Affiliation(s)
- Ahmad H Ali
- a 1 Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA
| | - Elizabeth J Carey
- a 1 Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA
| | - Keith D Lindor
- a 1 Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA.,b 2 Arizona State University, College of Health Solutions, Phoenix, AZ, USA
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Bekki N, Bae SK, Yoshizawa S, Shiota A, Gushima T, Motoshita J, Shimoda S, Aiba Y, Komori A, Nakamura M, Takahashi K. A case of primary biliary cirrhosis in a patient with rheumatoid arthritis. Clin Case Rep 2016; 4:90-4. [PMID: 26783445 PMCID: PMC4706410 DOI: 10.1002/ccr3.449] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 09/09/2015] [Accepted: 10/25/2015] [Indexed: 01/26/2023] Open
Abstract
The true prevalence of PBC in RA is not well known. Herein, we report an unusual case of a patient with PBC and RA, and discuss the association between these two diseases. PBC should be ruled out in the differential diagnosis of patients with RA having abnormal liver function tests.
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Affiliation(s)
- Norifumi Bekki
- The center for liver disease Hamanomachi Hospital 3-3-1 Nagahama Chuo-ku Fukuoka 810-8539 Japan
| | - Sung Kwan Bae
- The center for liver disease Hamanomachi Hospital 3-3-1 Nagahama Chuo-ku Fukuoka 810-8539 Japan
| | - Seiji Yoshizawa
- Department of Rheumatology Hamanomachi Hospital Fukuoka Japan
| | - Ayaka Shiota
- The center for liver disease Hamanomachi Hospital 3-3-1 Nagahama Chuo-ku Fukuoka 810-8539 Japan
| | - Toshifumi Gushima
- The center for liver disease Hamanomachi Hospital 3-3-1 Nagahama Chuo-ku Fukuoka 810-8539 Japan
| | | | - Shinji Shimoda
- Medicine and Biosystemic Science Kyushu University Fukuoka Japan
| | - Yoshihiro Aiba
- Clinical Research Center National Hospital Organization (NHO) Nagasaki Medical Center Nagasaki Japan
| | - Atsumasa Komori
- Clinical Research Center National Hospital Organization (NHO) Nagasaki Medical Center Nagasaki Japan
| | - Minoru Nakamura
- Clinical Research Center National Hospital Organization (NHO) Nagasaki Medical Center Nagasaki Japan
| | - Kazuhiro Takahashi
- The center for liver disease Hamanomachi Hospital 3-3-1 Nagahama Chuo-ku Fukuoka 810-8539 Japan
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Infliximab as a treatment option for patients with rheumatoid arthritis and primary biliary cirrhosis. Rheumatol Int 2015; 35:1913-6. [PMID: 26411882 DOI: 10.1007/s00296-015-3366-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Accepted: 09/17/2015] [Indexed: 12/19/2022]
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease which commonly requires treatment with biologic agents targeting various inflammatory pathways. Tumor necrosis factor alpha is a proinflammatory cytokine which plays a pivotal role not only in the pathogenesis of RA but also in other autoimmune diseases such as primary biliary cirrhosis. The co-existence of more than one autoimmune disorder in the same individual is very challenging in the daily practice as therapy strategies applicable to one disease setting may cause clinical and/or biochemical relapse of the other clinical entity. As a result, treatment options able to control different diseases are highly desirable among rheumatologists and other specialties. In that respect, we present a case of a 61-year-old female patient with RA and concomitant primary biliary cirrhosis with poor clinical response to conventional disease-modifying drugs for RA. The introduction of tumor necrosis factor alpha antagonist infliximab led to significant clinical improvement of RA and to stabilization of liver function. In this case review study, we discuss aspects of pathophysiology of primary biliary cirrhosis associated with tumor necrosis alpha and we review the available data of similar published cases.
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Kikuchi T, Hirano K, Genda T, Tsuzura H, Sato S, Kanemitsu Y, Narita Y, Iijima K, Ichida T. A study of the effects of saliva stimulation by nizatidine on dry mouth symptoms of primary biliary cirrhosis. World J Hepatol 2013; 5:90-6. [PMID: 23556039 PMCID: PMC3612578 DOI: 10.4254/wjh.v5.i3.90] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2012] [Revised: 08/15/2012] [Accepted: 11/14/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To elucidate the effect of saliva stimulation by nizatidine on oral symptoms of primary biliary cirrhosis (PBC) by administering it to PBC cases. METHODS From among 73 cases that had been definitively diagnosed as PBC at our hospital by February 2010, we selected 27 cases of PBC, 4 males and 23 females, as subjects. We obtained subjects' consent after giving them a full explanation of the administration of nizatidine. Nizatidine 150 mg was administered internally twice daily, after morning and evening meals. To observe changes in the quantity of saliva secreted, chewing gum tests were carried out four times: before the initial dose, and after 6 mo, 12 mo and 24 mo of administration. For subjective dry mouth symptoms, a visual analog scale (VAS) method was used to assess their feelings of oral dryness and eating difficulty, five times: before the initial dose, and after 1, 6, 12 and 24 mo of administration in 8 cases. The nutritional condition and the hepatic functional reserve were compared between before and after the nizatidine treatment. RESULTS The result of a chewing gum test on the subjects before the administration of nizatidine showed that 50% produced less than 10 mL of saliva, i.e., the standard under which cases are considered to have hyposalivation. The results of these tests showed that the quantity of saliva secreted was 10.5 ± 6.8 mL before administration of nizatidine, 10.9 ± 6.0 mL after 6 mo, 10.6 ± 4.9 mL after 12 mo, and 11.8 ± 6.8 mL after 24 mo administration. Thus, there was a slowly increasing trend in the quantity of saliva in the whole group. The percentage of subjects with saliva production above 10 mL was 45.8% after 6 mo administration of nizatidine, that is, only a slight change from before its administration, but it was 64.3% after 12 mo, that is, a significant increase. The saliva secretion by subject patients was examined before the beginning of administration of nizatidine, 12 mo later, and 24 mo later, and Fisher's combined probability test was used to examine the results for increases in saliva secretion. The analysis yielded P values of 0.51 and 0.53 for 12 mo later and 24 mo later, respectively. Thus, although there was no statistically significant increase, it was confirmed that saliva secretion tended to increase. A VAS method was employed to study the intensities of subjective symptoms of oral dryness and eating difficulty. Almost every case indicated some improvement of subjective oral dryness on the VAS early in the administration, i.e., one month after. We also studied the effects of the administration of nizatidine on nutritional condition, hepatic functional reserve, and long-term prognosis of PBC. No significant improvements in cholinesterase (ChE) level, albumin (Alb) level, or Child-Pugh score were found during the period of observation from the beginning to the end of administration of nizatidine, nor in comparison with the non-administration group. A comparative analysis between before administration and 24 mo later yielded P values of 0.41 for Alb, 0.56 for ChE, and 0.59 for the Child-Pugh scores. CONCLUSION It was confirmed that administering nizatidine to cases of PBC with dry mouth increased the secretion of saliva and improved the symptoms.
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Affiliation(s)
- Tetsu Kikuchi
- Tetsu Kikuchi, Katsuharu Hirano, Takuya Genda, Hironori Tsuzura, Shunsuke Sato, Yoshio Kanemitsu, Yutaka Narita, Katsuyori Iijima, Takafumi Ichida, Department of Gastroenterology and Hepatology, Juntendo University, Shizuoka Hospital, Shizuoka 410-2295, Japan
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Rheumatoid arthritis and primary biliary cirrhosis: cause, consequence, or coincidence? ARTHRITIS 2012; 2012:391567. [PMID: 23150824 PMCID: PMC3488395 DOI: 10.1155/2012/391567] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/28/2012] [Accepted: 09/28/2012] [Indexed: 12/14/2022]
Abstract
Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease characterized serologically by cholestasis and the presence of high-titre antimitochondrial antibodies and histologically by chronic nonsuppurative cholangitis and granulomata. PBC patients often have concomitant autoimmune diseases, including arthropathies. This raises the question as to whether there are shared features in the pathogenesis of those diseases with the pathogenesis of PBC. Epidemiological and large case studies have indicated that although the incidence of rheumatoid arthritis (RA) is not significantly raised in PBC patients, there appears to be a higher rate of RA in PBC patients and their relatives. Genetic studies have demonstrated that several genes implicated in PBC have also been implicated in RA. Epigenetic studies provided a wealth of data regarding RA, but the findings on epigenetic changes in PBC are very limited. As well, certain infectious agents identified in the pathogenesis of PBC may also play a role in the pathogenesis of RA. These data suggest that although RA is not significantly present in PBC, some individuals with certain genetic traits and environmental exposures may develop both conditions. This concept may also apply to other concomitant diseases found in PBC patients.
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TRAF1 gene polymorphism correlates with the titre of Gp210 antibody in patients with primary biliary cirrhosis. Clin Dev Immunol 2012; 2012:487521. [PMID: 23125866 PMCID: PMC3485529 DOI: 10.1155/2012/487521] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2012] [Accepted: 09/22/2012] [Indexed: 12/25/2022]
Abstract
Background. Polymorphisms of TRAF1 (Tumor necrosis factor receptor-associated factor 1) are associated with rheumatoid arthritis (RA). Whether TRAF1 polymorphisms confer increased risk for primary biliary cirrhosis (PBC), an autoimmune liver disease which can co-exist with RA, is unknown.
Aim of the Study. To assess the frequency of the RA-conferring susceptibility TRAF1 polymorphisms rs3761847 and rs2900180 in a cohort of PBC patients. The association of TRAF1 polymorphisms with clinical features and autoantibody markers was also analyzed.
Methods. We studied 179 PBC patients and 300 controls. Samples were genotyped for TRAF1 gene polymorphisms by real-time PCR. Autoantibodies were tested by ELISA.
Results. The frequency of rs3761847 and rs2900180 polymorphisms did not differ between patients and controls. Laboratory or clinical features were not associated with specific polymorphisms. Gp210 autoantibody titres were conspicuously higher among GG homozygotes of rs3761847 as compared with AA homozygotes (P = 0.02). In contrast, antichromatin titers were higher in AA compared to GG rs3761847 homozygotes (P = 0.04). Rheumatoid factor IgG titres were significantly higher in rs2900180 TT homozygotes than CC homozygotes (P = 0.02).
Conclusions. TRAF1 polymorphisms occur with the similar frequency in PBC patients and in the general population, but their presence is probably involved in the regulation of specific PBC-related autoantibodies.
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Hu CJ, Song G, Huang W, Liu GZ, Deng CW, Zeng HP, Wang L, Zhang FC, Zhang X, Jeong JS, Blackshaw S, Jiang LZ, Zhu H, Wu L, Li YZ. Identification of new autoantigens for primary biliary cirrhosis using human proteome microarrays. Mol Cell Proteomics 2012; 11:669-80. [PMID: 22647870 DOI: 10.1074/mcp.m111.015529] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown etiology and is considered to be an autoimmune disease. Autoantibodies are important tools for accurate diagnosis of PBC. Here, we employed serum profiling analysis using a human proteome microarray composed of about 17,000 full-length unique proteins and identified 23 proteins that correlated with PBC. To validate these results, we fabricated a PBC-focused microarray with 21 of these newly identified candidates and nine additional known PBC antigens. By screening the PBC microarrays with additional cohorts of 191 PBC patients and 321 controls (43 autoimmune hepatitis, 55 hepatitis B virus, 31 hepatitis C virus, 48 rheumatoid arthritis, 45 systematic lupus erythematosus, 49 systemic sclerosis, and 50 healthy), six proteins were confirmed as novel PBC autoantigens with high sensitivities and specificities, including hexokinase-1 (isoforms I and II), Kelch-like protein 7, Kelch-like protein 12, zinc finger and BTB domain-containing protein 2, and eukaryotic translation initiation factor 2C, subunit 1. To facilitate clinical diagnosis, we developed ELISA for Kelch-like protein 12 and zinc finger and BTB domain-containing protein 2 and tested large cohorts (297 PBC and 637 control sera) to confirm the sensitivities and specificities observed in the microarray-based assays. In conclusion, our research showed that a strategy using high content protein microarray combined with a smaller but more focused protein microarray can effectively identify and validate novel PBC-specific autoantigens and has the capacity to be translated to clinical diagnosis by means of an ELISA-based method.
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Affiliation(s)
- Chao-Jun Hu
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100032, China
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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.
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Affiliation(s)
- Joaquim Polido-Pereira
- Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
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Walker EJ, Hirschfield GM, Xu C, Lu Y, Liu X, Lu Y, Coltescu C, Wang K, Newman WG, Bykerk V, Keystone EC, Mosher D, Amos CI, Heathcote EJ, Siminovitch KA. CTLA4/ICOS gene variants and haplotypes are associated with rheumatoid arthritis and primary biliary cirrhosis in the Canadian population. ACTA ACUST UNITED AC 2009; 60:931-7. [PMID: 19333938 DOI: 10.1002/art.24412] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
OBJECTIVE The co-occurrence of different autoimmune diseases in patients and their families suggests the presence of shared genetic risk factors. Two compelling candidate autoimmune disease susceptibility genes are those that encode CTLA4 and inducible costimulator (ICOS), immunoregulatory proteins. Associations of CTLA4 polymorphisms with various autoimmune diseases have been reported, but for rheumatoid arthritis (RA) and primary biliary cirrhosis (PBC), the association data are inconsistent and have largely excluded analysis of polymorphisms in the ICOS gene adjacent to CTLA4. We undertook this study to examine whether CTLA4 and ICOS influence RA and PBC susceptibility by testing CTLA4/ICOS polymorphisms for association with these diseases in Canadian subjects. METHODS Caucasian RA patients (n = 1,140), PBC patients (n = 481), and controls (n = 1,248) were typed for 21 biallelic polymorphisms across the CTLA4/ ICOS genes using a multiplex genotyping array, and the results were analyzed using a false discovery rate method to correct for multiple testing. RESULTS Significant associations of multiple CTLA4 and ICOS gene polymorphisms with RA and PBC were observed, with the strongest association signals for both diseases coming from a CTLA4/ICOS intergenic single-nucleotide polymorphism, rs17268364 (corrected P [P(corr)] = 6.0 x 10(-4) and P(corr) < 1.0 x 10(-4), respectively). Significant associations, which were common to both diseases, were also observed with other alleles and haplotypes across 3 linkage disequilibrium blocks within the CTLA4 gene, the intergenic region, and the ICOS gene. CONCLUSION Our results provide evidence for RA and PBC association with the CTLA4/ICOS locus and suggest that the risk allele(s) within this region may be common to both diseases.
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Affiliation(s)
- Erin J Walker
- University of Toronto, Toronto General Hospital, and Mount Sinai Hospital, Toronto, Ontario, Canada
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