Background Interstitial lung disease (ILD) is associated with a significant morbidity and mortality in systemic sclerosis (SSc). Many studies have reported the association between human leukocyte antigen (HLA) alleles and increased risk of SSc, but the associated between ILD in SSc and HLA alleles remains unclear.
Objectives The aim of this study was to investigate the association of HLA class I and HLA class II with ILD in Korean SSc cohort.
Methods A total of 170 SSc patient (105 SSc patients with ILD and 65 SSc patients without ILD) were enrolled at Seoul National University Hospital from 1988 to 2014. Two hundred one healthy participants from Korean Marrow Donor Program (KMDP) were recruited as controls. Demographic information, clinical skin subset (limited vs. diffuse), SSc-specific autoantibodies (anti-topoisomerase I (ATA), anti-centromere (ACA), anti-ribonucleoprotein (RNP)), and internal organ involvement (ILD, pulmonary arterial hypertension, gastrointestinal, renal involvement) of the enrolled patients were characterized. ILD were diagnosed based on the findings of the chest computed tomography. HLA-A, -B, -C,-DQB1,-DRB1, and -DPB1 typing were performed PCR amplification with directly sequencing from extracted genomic DNA.
Results HLA-B*52:01, C*12:02, DRB1*15:02, DPB1*09:01, and DPB1*13:01 alleles were more frequent in SSc patients with ILD than healthy controls. However, the frequencies of these genes did not differ between SSc patients with and without ILD (Table). ATA positive SSc was associated with HLA-B*52:01, C*12:02, DRB1*15:02, DPB1*09:01, and DPB1*13:01 alleles compared to ATA negative SSc and DPB1*09:01 showed the highest odds ratio for ATA (OR =23.08).
Conclusions SSc patients with ILD have several specific HLA genes compared with healthy controls and the frequencies of these HLA genes were significantly higher in ATA-positive SSc as well. Therefore, ATA positivity and ILD are associated with ceratin HLA class I and II in SSc patients.
Zhou X, Lee JE, Arnett FC, Xiong M, Park MY, Yoo YK, et al. HLA-DPB1 and DPB2 are genetic loci for systemic sclerosis: a genome-wide association study in Koreans with replication in North Americans. Arthritis Rheum 2009;60:3807–14.
Disclosure of Interest None declared