The amino acid variants in HLA II molecules explain the major association with adult-onset Still's disease in the Han Chinese population.

Abstract Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease with systemic involvement, and its pathophysiology remains unclear. Genome-wide association studies (GWAS) in the Chinese population have revealed an association between AOSD and the major histocompatibility complex (MHC) locus; however, causal variants in the MHC remain undetermined. In the present study, we identified independent amino-acid polymorphisms in human leukocyte antigen (HLA) molecules that are associated with Han Chinese patients with AOSD by fine-mapping the MHC locus. Through conditional analyses, we identified position 34 in HLA-DQα1 (p = 1.44 × 10−14) and Asn in HLA-DRβ1 position 37 (p = 5.12 × 10−11) as the major determinants for AOSD. Moreover, we identified the associations for three main HLA class II alleles: HLA-DQB1*06:02 (OR = 2.70, p = 3.02 × 10−14), HLA-DRB1*15:01 (OR = 2.44, p = 3.66 × 10−13), and HLA-DQA1*01:02 (OR = 1.97, p = 1.09 × 10−9). This study reveals the relationship between functional variations in the class II HLA region and AOSD, implicating the MHC locus in the pathogenesis of AOSD.