Defining Immunogenomic Signatures in B Cell-Mediated Autoimmunities

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B605
Abstract ID: 5570

Presenting Author:
Easton E Ford , Graduate Student at Univ. of Louisville Sch. of Med.

Abstract:

A hallmark of B cell-mediated autoimmune disorders is the production of autoreactive antibodies (aAb). We hypothesize that pathogenic mechanisms of these aAbs are associated with unique immunogenomic signatures, reflected by biased variable (V), diversity (D), joining (J), and/or constant (C) allele usage and residue signatures associated with effector functions in the immunoglobulin heavy chain (IGH). Here we define the initial immunogenomic background of three IgG aAb B cell autoimmune diseases: Acetylcholine Receptor Myasthenia Gravis (AChR MG n=7), Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD n=4) and Neuromyelitis Optica Spectrum Disorder (NMOSD n=4) using a suite of immunogenomics tools including IGcapture for ground truth genotyping of the IGH locus and FLAIRR-seq for near full-length IGH repertoire profiling from RNA. From initial profiling of the IGHC region, a total of 15 novel alleles were discovered across IgG subisotypes. Extensive repertoire profiling across disease types revealed numerous discernible trends in the utilization frequency of IgG IGHC and IGHV genes when comparing to those from healthy donors. Additionally, statistically significant differences (p-value=0.05) in IGHV gene usage within IgG subisotypes were evident across each disease-specific group, despite small initial sample numbers. Collectively, with these data we are beginning to define how IGH genomic variation may be associated with B cell autoimmunities.