HLA polymorphisms potentially associated with susceptibility to chronic post-chikungunya inflammatory joint disease:...

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.

To explore associations between HLA alleles and progression to pCHIKV-CIJD in a Brazilian cohort.

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.

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.

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.