Association of the HLA-DRB1 with Scleroderma in Chinese Population

Abstract

Multiple alleles of the Human leukocyte antigen (HLA) DRB1 have been strongly associated with systemic sclerosis (SSc) and its clinical or serological subsets. However, the associations vary in different ethnic populations. To define SSc-risk and/or -protective alleles of HLA-DRB1 in Chinese population, we studied a Han Chinese cohort containing 585 patients with SSc and 458 gender-matched, unrelated controls. The HLA-DRB1 genotyping was performed with sequence-based typing method. Exact p-values were obtained (Fisher’s test) from 2×2 tables of allele frequency and disease status. The major SSc-risk allele subtypes of HLA-DRB1 are the DRB1*15∶02 and *16∶02 in this Chinese cohort. Particularly, DRB1*15∶02 was most significantly associated with anti-centromere autoantibodies (ACA) positive, and DRB1*16∶02 with anti-topoisomerase I autoantibodies (ATA) positive patients. On the other hand, DRB1*01∶01 and *04∶06 were strong SSc-protective alleles in Chinese, especially in patients who were ACA positive and had diffuse cutaneous SSc (dcSSc), respectively. In addition, DRB1*11 and *07∶01 also showed significant association with SSc as a risk for and protection from SSc, respectively, and which is consistent with the studies of Spanish, US Caucasian and Hispanic populations. DRB1*15 was associated with ATA positive Chinese SSc that is consistent with Black South African and Korean SSc. These findings of HLA-DRB1 alleles in association with Chinese SSc provide the growing knowledge of genetics of SSc, and indicate that the genetic heterogeneity among ethnicities may significantly impact the complex trait of SSc.

Brief Report: HLA–DRB1, DQA1, and DQB1 in Juvenile‐Onset Systemic Sclerosis

“…To our knowledge this is the first description of an association of DRB1*10 with disease in an SSc population overall, as well as in a Caucasian population. It is noteworthy that in a study of a Chinese population, the frequency of DRB1*10 was increased in a secondary analysis restricted to ACA‐positive patients .…”

HLA class II alleleDRB1*16:02is associated with anti-NMDAR encephalitis

“…Our results demonstrate for the first time that the HLA class II allele DRB1*16:02 is associated with disease susceptibility and therapeutic response of patients with anti-NMDAR encephalitis. The DRB1*16:02 allele has previously been shown to be associated with an increased risk of multiple autoimmune diseases, including Graves’ disease,23 anti-topoisomerase I autoantibody-positive systemic sclerosis,24 anti-aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder,25 relapsing polychondritis26 and primary Sjögren’s syndrome 27. Interestingly, all of these autoimmune diseases associated with the DRB1*16:02 are predominantly mediated by autoantibodies, suggesting that the DRB1*16:02 as an HLA class II molecule is involved in the autoantibody production.…”

HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications

“…In dermatomyositis, carriage of anti-Mi-2 (a nuclear antigen) antibodies is associated with HLA-DRB1*07:01, whereas carriage of anti-TIF1- (transcription intermediary factor 1) antibodies is associated with HLA-DQB1*02 199 . In systemic sclerosis, the two main serological patient subsets, defined by carriage of anti-centromere antibodies (anti-CA) or antitopoisomerase antibodies (anti-Topo I), also are distinguished by genetic differences at HLA class II loci 35,200 : for example, DRB1*15:02 (anti-CA) and DRB1*16:02 (anti-Topo I) in the Han Chinese population 200 .…”