HLA polymorphisms potentially associated with susceptibility to chronic post-chikungunya inflammatory joint disease: an exploratory study

BACKGROUND: A substantial proportion of Chikungunya virus (CHIKV)-infected patients progress to post-Chikungunya chronic inflammatory joint disease (pCHIKV-CIJD), yet host genetic determinants of this outcome remain poorly understood. HLA polymorphisms are established risk factors for inflammatory arthropathies, but their role in CHIKV chronification has not been investigated. OBJECTIVES: To explore associations between HLA alleles and progression to pCHIKV-CIJD in a Brazilian cohort. STUDY DESIGN: We performed in silico HLA typing from whole-blood RNA-seq data of 59 CHIKV-infected patients (32 pCHIKV-CIJD and 27 non-pCHIKV-CIJD) using HLAminer. We compared allelic frequencies at two-digit resolution using Fisher's exact test with Bonferroni correction. Additional analyses included supertype classification, heterozygosity scoring, KIR ligand grouping, and logistic regression adjusted for sex, age, and race. RESULTS: HLA-A02 was enriched among pCHIKV-CIJD patients (35.9% vs. 14.8%; OR = 3.19, 95% CI: 1.21-9.21, p = 0.012), remaining nominally significant after covariate adjustment (adjusted OR = 3.57, 95% CI: 1.09-11.73, p = 0.036). The B62 supertype was also more frequent in the chronic group (15.6% vs. 3.7%; OR = 4.76, 95% CI: 0.95-46.73, p = 0.037). Chronic patients showed lower HLA heterozygosity (p = 0.043). However, no association survived the Bonferroni correction. CONCLUSIONS: Our data support a potential association between HLA-A02 carriage and an increased risk of pCHIKV-CIJD. These findings are hypothesis-generating and require validation in larger, independent cohorts.