HLA − C*03:02:02 and DPA1*01:03:01 protect against discoid rash in Thai Systemic Lupus Erythematosus patients

This study aims to characterized high-resolution HLA alleles in Thai SLE patients and investigate their clinical correlations.The 6 digits HLA allele imputation was conducted using previously published Thai genotyping array data (SLE = 892, healthy controls = 1,638), utilizing population-matched HLA sequencing data as reference (n = 381). The HLA genes (HLA-A, HLA-C, HLA-B, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1, HLA-DPB1) was imputed independently using HIBAG R package. Case–control analysis, haplotype analyses, and clinical correlations were performed using the BIGDAWG R package. Our imputation replicates previously reported associations in Thai SLE patients and further refines the implicated alleles to 6 digits, including DRB1*15:02:01, DRB1*12:02:01, DQB1*05:01:24 and DQB1*03:01:01. Two novel HLA class II alleles were identified, including DQA1*01:01:01 (Pc = 3.74E-09, OR = 1.83 [1.51–2.22]) and DPA1*02:01:01 (Pc = 1.77E-04, OR = 1.40 [1.19–1.66]). Haplotype analysis revealed that DQA1*01:01:01 ~ DQB1*05:01:24 conferred an increased risk for SLE (Pc = 5.64E-11, OR = 1.98 [1.62–2.42]). Clinical correlation showed haplotype B*58:01:01 ~ C*03:02:02 were protective against discoid rash (Pc < 0.05, OR = 0.47 [0.25–0.83]). This study highlights the utility of microarray data in generating high-resolution HLA alleles and conducting association analyses, which may facilitate the prognosis marker for SLE-related skin manifestations.