Genetic Polymorphism and Intravenous Immunoglobulin Resistance Relationship in Kawasaki Disease

Abstract

Background Kawasaki disease (CD) is an acute febrile systemic vasculitis that is the most common cause of coronary artery aneurysm (CAA) in children. Resistance to IVIG, which is used to reduce the risk of developing CAA, is an important risk factor, and risk scoring systems used to predict the development of this resistance gave different results in different breeds. We planned our study to investigate the effect of genetic factors on the development of IVIG resistance. Methods Patients diagnosed with CD by whole exome gene analysis were analyzed retrospectively. Blood samples were obtained from a randomized subgroup (n:97). Previously reported IVIG resistance-associated exonic SNPs at five different gene loci (IL16,TNFSF14, NFATC2,DERL3,SAMD9L) were evaluated by whole-exome sequencing(WES). Results 259 patients (male/female: 1.67) with CD were included in the study. The rates of CAA and IVIG resistance in our patients were 11.6% and 21.6%, respectively. The risk of developing CAA was significantly increased in patients with IVIG resistance (p < 0.001). As a result, IVIG resistance frequency increased in the presence of three SNPs (the IL16,TNFSF14, NFATC2 genes, respectively). Conclusion The development of resistance at different rates in different races against IVIG, which is used in the treatment of CD, has led to genetic studies. In our study, we found mutations in three genes (IL16, TNFSF14, NFATC) that play a role in T lymphocyte activation in patients with IVIG resistance. We think that the role of genetic factors in the resistance mechanism will become clear with the increase in genetic studies to be done.