Predominant HLA class I associations with lupus nephritis susceptibility, histology class and reduced renal function...

To investigate associations between (human leukocyte antigen) HLA alleles and overall lupus nephritis (LN) susceptibility, biopsy-defined histologic classes and reduced renal function in Taiwanese patients with systemic lupus erythematosus (SLE). We conducted a retrospective case-control study using data from the Taiwan Precision Medicine Initiative. The matched cohort included 388 SLE patients with biopsy-confirmed LN and 381 SLE patients without LN. HLA alleles were imputed from single nucleotide polymorphism (SNP) array data using HIBAG. Multivariable logistic regression was employed to evaluate associations of candidate HLA alleles with LN overall, individual LN histologic classes and reduced renal function within LN, adjusting for age, gender, hypertension and diabetes mellitus. The study included 388 biopsy-confirmed LN cases and 381 matched SLE controls without LN. Four alleles were independently associated with overall LN susceptibility, including HLA-B*13:01 (adjusted OR 1.68, 95% CI 1.09-2.59), HLA-B*58:01 (1.69, 1.15-2.49), HLA-C*03:02 (1.75, 1.19-2.58) and HLA-DRB1*03:01 (1.51, 1.01-2.27). Class-specific analyses showed that HLA-B*13:01 was associated with Class I/II LN; HLA-B*58:01 and HLA-C*03:02 with Class III ± V LN; and HLA-B*13:01, HLA-B*58:01, and HLA-C*03:02 with Class IV ± V LN. No allele remained independently associated with Class V LN after full adjustment. Within the LN cohort, HLA-B*13:01 was the only allele associated with reduced renal function (eGFR < 60 mL/min/1.73 m²; adjusted OR 2.24, 95% CI 1.30-3.85). Overall, the strongest associations were observed for HLA class I alleles, particularly HLA-B*13:01 in this study. In Taiwanese patients with SLE, a narrower set of predominantly HLA class I alleles is associated with LN susceptibility and proliferative LN phenotypes. HLA-B*13:01 showed the most consistent association across overall LN susceptibility, histologic severity and reduced renal function.