Scientists who analyzed the genes involved in 10 autoimmune diseases that begin in childhood have discovered 22 genome-wide signals shared by 2 or more diseases. These shared gene sites may reveal potential new targets for treating many of these diseases, in some cases with existing drugs already available for non-autoimmune disorders. Autoimmune diseases, eg Type 1 diabetes, Crohn’s disease, and juvenile idiopathic arthritis, collectively affect 7 to 10% of the Western Hemisphere.
Meta-analysis was performed, incl a case-control study of 6,035 subjects with automimmune disease and 10,700 controls, all of European ancestry. Yun (Rose) Li, M.D./Ph.D. applied highly innovative and integrative approaches in supporting the study of pathogenic roles of the genes uncovered across multiple diseases. 10 clinically distinct autoimmune diseases with onset during childhood were studied: type 1 diabetes, celiac disease, juvenile idiopathic arthritis, common variable immunodeficiency disease, SLE, Crohn’s disease, ulcerative colitis, psoriasis, autoimmune thyroiditis and ankylosing spondylitis.
Previous genome-wide studies identified hundreds of susceptibility genes among autoimmune diseases, largely affecting adults. This study team found 27 genome-wide loci, including 5 novel loci. Of those 27 signals, 22 were shared by at least 2 of the autoimmune diseases, and 19 of them were shared by at least 3 of them.
Many of the gene signals the investigators discovered were on biological pathways functionally linked to cell activation, cell proliferation and signaling systems important in immune processes. 1 of the 5 novel signals, near the CD40LG gene, was especially compelling, said Hakonarson, who added, “That gene encodes the ligand for the CD40 receptor, which is associated with Crohn’s disease, ulcerative colitis and celiac disease. This ligand may represent another promising drug target in treating these diseases.”
“Rather than looking at overall gene expression in all cells, we focused on how these genes upregulated gene expression in specific cell types and tissues, and found patterns that were directly relevant to specific diseases. For instance, among several of the diseases, we saw genes with stronger expression in B cells. Looking at diseases such as lupus or juvenile idiopathic arthritis, which feature dysfunctions in B cells, we can start to design therapies to dial down over-expression in those cells.”
Level of granularity the study team uncovered offers opportunities … to better target gene networks and pathways in specific autoimmune diseases, and perhaps to fine tune and expedite drug development by repurposing existing drugs. http://www.chop.edu/news/genetic-overlapping-multiple-autoimmune-diseases-may-suggest-common-therapies
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