Massively multiplexed serology of inflammatory bowel disease demonstrates association with pentose phosphate shunt autoantibodies 3394

Abstract Description Introduction Recent advances in high-throughput synthetic biology tools enable massively multiplexed serologic antibody profiling. We apply these tools to investigate inflammatory bowel diseases (IBD). Methods To determine antibody repertoires in IBD, we analyzed serum samples from pediatric controls (N = 30), Crohn’s (N = 30), ulcerative colitis (N = 40), severe ulcerative colitis (N = 28), and adult ulcerative colitis (N = 20). All 148 samples were analyzed using human proteome microarrays (HuProt, >21,000 proteins), human proteome PhIP-Seq (HuScan, >700,000 49-mer peptides), and pan-viral PhIP-Seq (VirScan, >480,000 62-mer peptides). Results HuProt microarray analysis revealed IBD patients frequently exhibited autoantibodies to pentose phosphate shunt pathway proteins (GO:0006098, GO:0009052). This was most pronounced in pediatric ulcerative colitis versus controls (BH-corrected p = 5.08E-05), with nearly all patients showing IgG autoantibodies against at least one of RPIA, TALDO1, PGD, or TKT. Similar reactions were observed in other IBD groups. The top IBD-associated viral antibody was against a peptide from Epstein-Barr virus. Conclusion Autoantibodies can permanently alter health through metabolic disruption; colitis treatments like Cyclosporine A are already thought to work via pentose phosphate pathway modulation of neutrophil behavior. These reported autoantibodies may be directly related to the mechanism of some inflammatory bowel conditions. Funding Sources None Topic Categories Basic Autoimmunity (BA)