Frontiers in Immunology (Sep 2023)

Human leukocyte antigen association in systemic sclerosis patients: our experience at a tertiary care center in North India

  • Sanghamitra Machhua,
  • Shefali Khanna Sharma,
  • Yashwant Kumar,
  • Surjit Singh,
  • Ritu Aggarwal,
  • Shashi Anand,
  • Manoj Kumar,
  • Heera Singh,
  • Ranjana Walker Minz

DOI
https://doi.org/10.3389/fimmu.2023.1179514
Journal volume & issue
Vol. 14

Abstract

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IntroductionSystemic sclerosis (SSc) is a chronic multisystem autoimmune rheumatic disease of unknown etiology. Several studies have established that SSc is triggered by a dynamic interplay between genetic factors and environmental stimuli. In the present study, we aimed to study the association of human leukocyte antigen (HLA) with familial and non-familial SSc patients [limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc)] from North India.MethodsThe HLA-A, B, DRB1, and DQB1 genotyping of 150 (70 lcSSc and 80 dcSSc) adult-onset SSc patients and 150 age-gender-matched healthy controls were performed with sequence-specific oligonucleotide (SSO) typing kits using the luminex platform. HLA typing for HLA class I (A, B, and C) and II (DRB1, DQB1, and DPB1) in five North Indian families consisting of parent–child/sibling pairs affected with SSc or overlap syndrome was performed by Next Generation Sequencing (NGS) with Illumina MiniSeq.RseultsAmong the non-familial SSc patients, HLA- DRB1*11 (P = 0.001, OR: 2.38, Pc = 0.01) was identified as a risk allele, and DRB1*12 (P = .0001, OR: 0.00, Pc = 0.001) as a protective allele. There was no statistical association found with HLA-DQB1*. Also, no significant association was observed between HLA antigens and different clinical subsets (lcSSc and dcSSc) of SSc. Two cases of familial SSc patients had the DRB1*11 allele. The DRB1*12 allele was absent in all the familial SSc patients. DiscussionHLA DRB1*11 (risk allele) and DRB1*12 (protective allele) were found to be strongly associated with non-familial SSc patients and partially explain the disease’s familial clustering, supporting the susceptible genetic background theory for SSc development. The study also indicates the HLA allele as a common genetic risk factor in distinct autoimmune diseases contributing to overlap syndrome or polyautoimmunity.

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