Genetic Polymorphism and Intravenous Immunoglobulin Resistance Relationship in Kawasaki Disease

Abstract Objective Kawasaki disease (KD) is an acute febrile systemic vasculitis and the most common cause of coronary artery aneurysm (CAA) in children. Intravenous immunoglobulin (IVIG) therapy is used to prevent fever and systemic inflammation. However, IVIG resistance is the most important risk factor of morbidity and mortality. It has been identified several single nucleotide polymorphisms (SNPs) related to IVIG resistance and this research aims to analyze these polymorphisms in our study population. Methods Patients diagnosed with KD (n:259) were analyzed retrospectively. Blood samples were taken from a randomized subgroup (n:97). Previously reported IVIG resistance related exonic SNPs at five different gene loci (IL16, TNFSF14, NFATC2, DERL3, SAMD9L) were evaluated by whole exome sequencing (WES). Results Between 2010–2019, 259 patients (male/female: 1,67) with KD were submitted to our clinic. CAA and IVIG resistance rates 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. These are "rs11556218"(p.Asn1147Lys), "rs344560"(p.Lys214Glu), "rs12479626"(p.His446Arg), and are located in IL16, TNFSF14, NFATC2 genes, respectively. Conclusions Until now, KD-related genetic data mostly obtained from studies involving large cohorts from Northeast Asian countries. In the analysis of this largest Turkish cohort in the literature, we found that, similar with previous studies, the IL16 gene may be plays important role in the IVIG resistance mechanism.