Executive Summary : | Rheumatic fever (RF) and rheumatic heart disease (RHD) are the autoimmune sequelae caused by group A Streptococcus (GAS). RHD still remains a major concern in the developing countries due to its poor diagnosis, lack of vaccines, and social awareness among populations. In the study, we aimed to identify the plausible early and late stage disease markers associated with RF/RHD. A total of 84 diagnostically confirmed pharyngitis, RF, and RHD patients from north India were included in the comparative analysis of different factors involved in host-pathogen interaction during RF/RHD pathogenesis. This study revealed high titre of serum antistreptolysin O antibody (ASO) in pharyngitis compared to RF and RHD patients, whereas, procollagen type 1C peptide (PICP) level was elevated in RHD, which showed an inverse correlation with serum ASO titre. The significant elevation of serum antiPARF antibody in RF patients can be correlated as a probable stage specific determinant. Additionally, proinflammatory cytokine profile revealed high levels of IL-12/IL-23p40, IL-17A in RF, whereas IL-6 concentration was higher in RHD. In addition to the serum cytokines, the MBL concentration was found to be significantly high in RF and pharyngitis, but, no polymorphisms were identified in the exon3 of the MBL-2 gene. Further, we extrapolated our study with KIR genotyping, which revealed an utmost regulation of NK cells during RF/RHD. The microRNA profiling revealed different up regulated and down regulated microRNAs RHD compared to control. In the forthcoming study, we would like to check the regulation of individual microRNA in RHD. The overall assessment of these factors involved in host-pathogen interaction may be suggestive of plausible disease marker in different groups of patients. Thus, the study might be a step forward in better understanding of RF/RHD pathogenesis. |