Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Front Immunol. 2023 Jan 18;13:984083. doi: 10.3389/fimmu.2022.984083. eCollection 2022.
Autoimmune hepatitis (AIH) is a chronic and progressive disease of the liver. This is a multifactorial autoimmune disease with both environmental factors and genetic factors playing a role in its pathogenesis. Certain environmental agents like viruses, drugs, etc., can trigger the disease in a genetically susceptible individual. The present study was aimed to explore the distribution of human leukocyte antigen (HLA)-DRB1, Protein tyrosine phosphatase non-receptor type 22 (PTPN22) and Cytotoxic T-Lymphocyte-associated protein 4 (CTLA-4) polymorphisms in North Indian adult AIH patients and their associations with clinical and pathological characteristics associated with the disease. A total of 147 subjects with 47 cases and 100 healthy controls were enrolled. Diagnosis of AIH was made by Revised International Autoimmune Hepatitis Group scoring system. HLA-DRB1 Typing was done by Luminex-based reverse Sequence-Specific Oligonucleotide Probing (SSOP). Single nucleotide variant (SNV) genotyping for CTLA-4 and PTPN22 was done by simple probe-based SNP arrays. Results indicated SLA positive AIH patients are poor responders to therapy. A significant predispositional association of HLA-DRB1*03 was observed in AIH patients from the North Indian population (p= 0.0001, OR=4.83 (2.30-10.15). The frequency of the GG genotype of CTLA-4 CT 60 was significantly increased in AIH patients compared to controls. Multinomial analysis showed that CTLA-4 CT 60 is an independent predictor for cases.
自身免疫性肝炎(AIH)是一种慢性进行性肝脏疾病。这是一种多因素自身免疫性疾病,环境因素和遗传因素在其发病机制中都起着作用。某些环境因子,如病毒、药物等,可在遗传易感个体中引发该病。本研究旨在探讨人类白细胞抗原(HLA)-DRB1、蛋白酪氨酸磷酸酶非受体型 22(PTPN22)和细胞毒性 T 淋巴细胞相关蛋白 4(CTLA-4)多态性在北印度成年 AIH 患者中的分布及其与与疾病相关的临床和病理特征的关联。共纳入 147 例受试者,其中 47 例为 AIH 患者,100 例为健康对照。采用修订后的国际自身免疫性肝炎组评分系统诊断 AIH。采用基于 Luminex 的反向序列特异性寡核苷酸探针(SSOP)进行 HLA-DRB1 分型。采用简单探针 SNP 阵列对 CTLA-4 和 PTPN22 的单核苷酸变异(SNV)进行基因分型。结果表明,SLA 阳性的 AIH 患者对治疗反应不佳。在北印度人群中,AIH 患者 HLA-DRB1*03 存在显著的易感性关联(p=0.0001,OR=4.83(2.30-10.15)。与对照组相比,AIH 患者 CTLA-4 CT 60 的 GG 基因型频率显著升高。多项分析表明,CTLA-4 CT 60 是病例的独立预测因子。