Relations between human leukocyte antigens and autoimmune hepatitis in Turkish children

Gulec, Seda Geylani; Urgancı, Nafiye; Polat, Tuğçin Bora; Demirel, Emirzad; Yılmaz, Erkan

doi:10.4318/tjg.2011.0155

Cited by 5 publications

(2 citation statements)

References 38 publications

(35 reference statements)

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“…However, this is not entirely surprising as the ancestry of the current Turkish population has roots mainly in central Asia. Yet, two Turkish studies investigated the HLA-DRB1 allele frequency in children or adult AIH patients ( 36 , 37 ). In adults, they found that 58% of patients had DR4 with the DR3 frequency being similar to our population 29%.…”

Section: Discussionmentioning

confidence: 99%

Standard immunosuppressive treatment reduces regulatory B cells in children with autoimmune liver disease

et al. 2023

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IntroductionAutoimmune hepatitis (AIH) is a chronic liver disease caused by a perturbed immune system. The scarcity of short- and long-term immune monitoring of AIH hampered us to comprehend the interaction between immunosuppressive medication and immune homeostasis.Methods and patientsWe recruited children with AIH at the time of diagnosis and at the 1st, 3rd, 6th, 12th, 18th, and 24th months of immunosuppression (IS). We also enrolled children with AIH being on IS for >2 years. Children with drug-induced liver injury (DILI), and those receiving tacrolimus after liver transplantation (LT), were enrolled as disease/IS control subjects. Healthy children (HC) were also recruited. Peripheral blood mononuclear cells (PBMCs) were isolated from all participants. Healthy liver tissue from adult donors and from livers without inflammation were obtained from children with hepatoblastoma. By using flow cytometry, we performed multi-parametric immune profiling of PBMCs and intrahepatic lymphocytes. Additionally, after IS with prednisolone, tacrolimus, rapamycin, or 6-mercaptopurine, we carried out an in vitro cytokine stimulation assay. Finally, a Lifecodes SSO typing kit was used to type HLA-DRB1 and Luminex was used to analyze the results.ResultsUntreated AIH patients had lower total CD8 T-cell frequencies than HC, but these cells were more naïve. While the percentage of naïve regulatory T cells (Tregs) (CD4+FOXP3lowCD45RA+) and regulatory B cells (Bregs, CD20+CD24+CD38+) was similar, AIH patients had fewer activated Tregs (CD4+FOXP3highCD45RA-) compared to HC. Mucosal-associated-invariant-T-cells (MAIT) were also lower in these patients. Following the initiation of IS, the immune profiles demonstrated fluctuations. Bregs frequency decreased substantially at 1 month and did not recover anymore. Additionally, the frequency of intrahepatic Bregs in treated AIH patients was lower, compared to control livers, DILI, and LT patients. Following in vitro IS drugs incubation, only the frequency of IL-10-producing total B-cells increased with tacrolimus and 6MP. Lastly, 70% of AIH patients possessed HLA-DR11, whereas HLA-DR03/DR07/DR13 was present in only some patients.ConclusionHLA-DR11 was prominent in our AIH cohort. Activated Tregs and MAIT cell frequencies were lower before IS. Importantly, we discovered a previously unrecognized and long-lasting Bregs scarcity in AIH patients after IS. Tacrolimus and 6MP increased IL-10+ B-cells in vitro.

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Section: Discussionmentioning

confidence: 99%

Standard immunosuppressive treatment reduces regulatory B cells in children with autoimmune liver disease

et al. 2023

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“…Similarly, the same loci have been implicated in other immune-mediated diseases. [19–21] Within the DQ loci, HLA-DQA1∗01 was associated with lower risk for NASH. Interestingly, DQA1∗01 has been linked to protection against HBV associated cirrhosis.…”

Section: Discussionmentioning

confidence: 99%

Analysis of human leukocyte antigen allele polymorphism in patients with non alcoholic fatty liver disease

et al. 2019

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The human leukocyte antigen (HLA) genes may play a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH). The aim of this study was to assess the association of HLA class I and II alleles with NASH and its histological features. Deoxyribonucleic acid (DNA) was extracted from 140 subjects (85 biopsy-proven NAFLD and 55 controls) and genotyped for HLA (-A, -B, -C, -DR1, -DR3, -DQ, and -DP). Liver biopsies were assessed for presence of NASH, degree of fibrosis and inflammation. Multivariate analysis was performed to assess associations between HLA genes and different histologic features of NAFLD. Our data for HLA class I showed that HLA-C∗4 was associated with lower risk for histologic NASH and HLA-C∗6 was protective against portal fibrosis. Conversely, HLA-B∗27 was associated with high-grade hepatic steatosis, while HLA-A∗31 was associated with increased risk for advanced fibrosis. Among HLA class II alleles, HLA-DQA1∗01 was associated with lower risk for NASH while HLA-DRB1∗03 was associated with increased risk for NASH. Our findings indicate that HLA class I and II gene polymorphism may be associated with susceptibility to NASH, fibrosis and other pathologic features and may be involved in the pathogenesis of NAFLD.

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Antibodies to soluble liver antigen in patients with various liver diseases: A multicentre study

Efe

Özaslan

Wåhlin

et al. 2013

Liver International

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Relations between human leukocyte antigens and autoimmune hepatitis in Turkish children

Cited by 5 publications

References 38 publications

Standard immunosuppressive treatment reduces regulatory B cells in children with autoimmune liver disease

Standard immunosuppressive treatment reduces regulatory B cells in children with autoimmune liver disease

Analysis of human leukocyte antigen allele polymorphism in patients with non alcoholic fatty liver disease

Antibodies to soluble liver antigen in patients with various liver diseases: A multicentre study

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