Acute Immunological Biomarkers for Predicting Chronic Rheumatism After Chikungunya Virus Infection

Early biomarkers are needed to predict the long-term persistence of rheumatic symptoms in patients infected with chikungunya virus (CHIKV). This nested case-control study aimed to assess immunological factors during the early phases of CHIKV infection to pre-dict the risk of post-CHIK chronic rheumatism (pCHIK-CR) in adult patients of two pro-spective cohorts. We evaluated 46 febrile patients (median age: 33.5 years, IQR:19 years; women: 50.0%) with CHIKV infection confirmed during the 2014-2015 outbreak in San-tander, Colombia. Participants were classified by a rheumatologist as either cases (pCHIK-CR) or controls (WoRM, without rheumatic manifestations). We quantified serum levels of IL-4, IL-6, IL-8/CXCL-8, IL-27, CCL-2, CXCL-9, CXCL-10 and IgG using Luminex and ELISA assays during the acute and subacute phases of infection. Then, we evaluated the association of these immune factors with the case-control status using piecewise lo-gistic regression adjusted for age and sex. There were non-linear associations between IL-8/CXCL-8, CXCL-9 and CXCL-10 with pCHIK-CR. Elevated levels of IL-8/CXCL-8 (< 35.7 pg/mL), CXCL-9 (≥2,000 pg/mL), CXCL-10 (≥36,800 pg/mL), significantly reduced the risk of pCHIK-CR (adjusted ORs: 0.85, 0.96 and 0.94, respectively). These results suggest that higher levels of IL-8/CXCL-8, CXCL-9 and CXCL-10, measured in the early stages of CHIKV infection, may predict chronic disease risk. This suggests that an early and strong immune response may enhance CHIKV control and reduce the risk of persistent joint symptoms. Given their expression patterns and timing, these three immune factors may be considered promising biomarker candidates for assessing the risk of chronic rheuma-tism. These findings should be validated in additional cohort studies.