No Evidence for Association Between ICOS (a T-Cell Co-Stimulatory Molecule) Gene Polymorphisms and Anti-MSP-1₁₉ IgG Response in Venezuelan Endemic Plasmodium vivax Malaria

The blood-stage merozoite surface protein 1 (PvMSP₁₉) of Plasmodium vivax is a key target of naturally acquired antibodies. Effective humoral responses depend on T-cell co-stimulation, notably via the inducible co-stimulator (ICOS) molecule. Polymorphisms in the ICOS gene may influence antibody production, yet this relationship remains unexplored in naturally infected populations. We analysed 91 individuals with uncomplicated P. vivax infection in Venezuela. Total IgG antibodies against recombinant PvMSP₁₉ were measured by ELISA. A two-step cluster analysis based on antibody reactivity indices (RI) was employed to categorize participants as low, medium, or high responders. Genotyping of ICOS polymorphisms (rs4404254, rs4675379 and rs10183087) was performed using PCR-based methods. Haplotype frequencies (inferred via the Expectation-Maximization algorithm), linkage disequilibrium (LD) and associations under various genetic inheritance models were assessed using Haplo.stats (R environment) and SNPStats. PvMSP₁₉-specific IgG was detected in 70.3% of participants. The optimal three-cluster solution (silhouette coefficient = 0.7) revealed significant differences in median RI across low (0.408), medium (0.862) and high responders (1.267; p < 0.001). ICOS genotypes and haplotypes showed no significant associations with antibody levels across any inheritance models, although strong LD was observed among the three loci (p < 0.05). Notably, antibody responses positively correlated with the number of prior malarial episodes (r = 0.803, p < 0.0001). Our results indicate that the studied ICOS polymorphisms do not significantly affect IgG responses against PvMSP₁₉ in this population, suggesting that variability in other costimulatory molecules may more strongly influence humoral immunity to P. vivax. These findings highlight the complexity of T-cell-mediated regulation of antibody responses and provide insights for optimizing vaccine strategies targeting blood-stage malaria antigens.