Tormin JPAS, Nascimento BR, Sable CA, et al. - This study was attempted to explore cytokine gene functional polymorphisms and phenotypic expression as predictors of evolution from latent to clinical rheumatic heart disease. Researchers enrolled a total of 212 individuals, 77 with latent, 100 with clinical rheumatic heart disease (RHD), and 35 healthy controls. They assessed circulating levels of 27 soluble factors applying Bio-Plex ProTM Human Cytokine Standard 27-plex assay. They conducted gene polymorphism analyses applying RT-PCR for the following genes: IL2, IL4, IL6, IL10, IL17A, TNF, and IL23. The data showed that IL-4, IL-8, and IL-1RA were the best predictors of clinical disease, despite higher levels of all cytokines in clinical RHD patients. They found an association of polymorphisms in IL2, IL4, IL6, and IL10 genes and clinical RHD. The findings revealed that the gene polymorphism and phenotypic expression of IL-4 accurately discriminate latent vs clinical RHD, potentially instructing clinical management.