Abstract Details

Title CD11c+ B cells Are Fundamentally Altered in Muscle-Specific Tyrosine Kinase Antibody Positive Myasthenia Gravis

Topic Autoimmune Neurology

Presentation(s) S5 - Autoimmune Neurology: NMOSD and MG, a Focus on Treatment Trials (2:48 PM-3:00 PM)

Poster/Presentation
Number 010

Objective

We hypothesized CD11c+ B cells influence the development of distinct IgG-producing B cells in AChR-MG and MuSK-MG.

Background Myasthenia gravis (MG) is a B cell-mediated autoimmune disease caused by antibodies that disrupt muscle-nerve communication resulting in muscle weakness. The majority of MG patients have mostly IgG1 and IgG3 antibodies against acetylcholine receptor (AChR-MG) and 5-8% have IgG4 antibodies against muscle-specific tyrosine kinase (MuSK-MG), resulting in variations in muscle weakness and treatment response. CD11c+ B cells are increased in autoimmune diseases and thought to be the precursors of antibody secreting cells. Understanding of this population of B cells may offer clues to the production of specific IgG subclasses.

Design/Methods

CD11c+ B cells were analyzed from AChR-MG (n=18), MuSK-MG (n=7), and control (n=12) subjects by flow cytometry. Gene expression analysis of ~800 immune-related genes was performed on CD11c+ and CD11c- B cells from 4 subjects per group.

Results CD11c+ B cells from all groups showed gene signatures associated with antibody-secreting cell development and activation of innate immune and T-cell signaling pathways, compared to CD11c^- B cells. AChR-MG and control CD11c+ B cells shared phenotypic and molecular characteristics but were distinct from MuSK-MG. MuSK-MG subjects had lower frequencies of CD11c+ B cells with reduced expression of CD11c+ B cell markers T-bet, CD95, and FCRL5. Gene expression analysis showed more than 100 genes, including genes in pathways associated with IgG1 class switching, cytosolic DNA sensing, cytoxicity, and T cell differentiation were significantly downregulated in MuSK-MG CD11c+ B cells compared to AChR-MG.

Conclusions The reduced population of CD11c+ B cell population in MuSK-MG patients along with the downregulation of genes associated with IgG1 class switching indicate an altered immune pathway is involved in the development of autoantibody producing cells. The mechanisms underlying the development of IgG1 in AChR-MG and IgG4 in MuSK-MG demonstrate these are two distinct diseases.

Authors/Disclosures
Patricia Sikorski, PhD (George Washington University) PRESENTER	Dr. Sikorski has nothing to disclose.
Henry J. Kaminski, MD, FAAN (George Washington University)	Dr. Kaminski has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Kaminski has received personal compensation in the range of $0-$499 for serving as a Consultant for Cabaletta Bio. The institution of Dr. Kaminski has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Kaminski has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Canopy Immunotherapeutics. Dr. Kaminski has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Curie.bio. Dr. Kaminski has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Samsung. Dr. Kaminski has received personal compensation in the range of $0-$499 for serving as a Consultant for Care Constitution. Dr. Kaminski has stock in mimivax. The institution of Dr. Kaminski has received research support from National Institutes of Health. Dr. Kaminski has received publishing royalties from a publication relating to health care.
	No disclosure on file

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