Exomic and transcriptomic analyses of Juvenile Dermatomyositis (JDM) and children Systemic Lupus Erythematosus (cSLE) by Whole Exome Sequencing (WES) and microarray 4510

Abstract Description Autoimmune disease in human is caused by breakdown of tolerance such that the immune system attacks self cells and tissues, leading to damage and injuries. We aim to compare genomic risk factors among patients with JDM and childhood onset cSLE. Genomic DNA from 51 JDM and 43 cSLE patients recruited at our study site were subjected to WES, using sequences in GnomAD for comparison. Analyses of WES data were performed by 2 × 2 Fisher’s exact test. We also compared patient’s clinical and microarray gene expression data. Top deleterious sequence variants identified among patients with JDM and cSLE were present in the complement, coagulation and platelet activation pathways. JDM patients have more mutations among genes related to platelet activation and complement regulation. Compared with healthy controls, patients with JDM have higher platelet counts (p = 3x10-12) but less platelet activation. cSLE have more variants engaged in activations of complement, coagulation and platelets. The Ser192Tyr of tyrosinase TYR was prevalent among JDM (patients: 41% vs controls: 25%). Arg402Gln is another variant of TYR that is prevalent among cSLE (patients: 32.6% vs controls: 17.6%). Both TYR variants are related to UV damage on the skin. For gene expression, both diseases are induced by IFN-α, although more severe in SLE. Among down-regulated genes, patients with cSLE feature genes engaged in gene expression, while patients with JDM have dysregulated genes in chemokine receptors and T cells. Funding Sources Supported by grants from the CureJM Foundation and NIAMS-NIH grant R01AR073311. Topic Categories Immune Mechanisms of Human Disease (HUM)