Abstract Details

Title Proteomic Analysis Reveals a Distinct Immunological Signature for Late-onset Myasthenia Gravis

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S15 - Autoimmune Neuromuscular Diseases: New Observations and Therapeutic Approaches (1:24 PM-1:36 PM)

Poster/Presentation
Number 003

Objective This exploratory in-depth proteomics analysis examined the differences in the immunopathogenesis of acetylcholine receptor (AChR) autoantibody-positive early onset (symptom onset < 50 years of age) and late-onset myasthenia gravis (EOMG and LOMG) utilizing the well-characterized BeatMG study (B-Cell Targeted Treatment in MG; NCT02110706) cohort.

Background MG is a heterogeneous autoimmune disease with autoantibodies against postsynaptic antigens at the neuromuscular junction. About 80% of patients with MG have autoantibodies against AChR, and their clinical features and treatment response may vary based on clinical characteristics. This investigation aimed to assess whether there was a unique signature based on symptom onset.

Design/Methods We used the Proximity Extension Assay (PEA) from the Olink platform to examine 768 inflammatory proteins in the baseline serum samples collected for the BeatMG study. After identifying the differentially expressed proteins, we performed enrichment analysis to assess the pathways involved with those proteins.

Results Baseline samples from 47 patients [age: 54.9 ± 17.7, 22 women (47%)] out of 52 patients from the BeatMG study with all necessary data points were included. Twenty patients were categorized as EOMG [38.4 ± 12.4, 15 women (75%)], and 27 were in the LOMG [67.1 ± 8.7, 7 women (25.9%)] category. The EOMG group had a higher percentage of thymectomy patients (55% vs. 0%, p-value <0.001). Principal component analysis showed separation of the EOMG and LOMG groups, and several proteins were highly expressed in the LOMG group, including CXCL17, JCHAIN, CD83, and TNFRSF11A. These proteins are involved in regulating leucocyte differentiation, interleukin-10 production, and myeloid leukocyte differentiation and migration pathways. TNFRSF11A SNP has been previously reported to be associated with LOMG.

Conclusions LOMG is potentially mediated by a distinct immunopathogenic mechanism. Further validation of these findings and an effort to identify tools to tailor therapeutic approaches for LOMG are warranted.

Authors/Disclosures
Bhaskar Roy, MD, FAAN (Yale University) PRESENTER	Dr. Roy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Roy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda Pharmaceuticals. Dr. Roy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for argenx. Dr. Roy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for argenx. Dr. Roy has stock in Cabaletta bio. . The institution of Dr. Roy has received research support from Martin Shubik Fund for IBM at Yale University. The institution of Dr. Roy has received research support from Abcuro Pharmaceuticals. The institution of Dr. Roy has received research support from Immunovant.
Fatemeh Khani Habiabadi	No disclosure on file
Kevin O'Connor (Yale University School of Medicine)	Kevin O'Connor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Kevin O'Connor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Kevin O'Connor has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Viela Bio. Kevin O'Connor has stock in Cabaletta.
Richard J. Nowak, MD (Yale University School of Medicine)	Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for argenx. Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Nowak has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Immunovant . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cabaletta Bio . Dr. Nowak has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cour Pharma. Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janseen . The institution of Dr. Nowak has received research support from UCB. The institution of Dr. Nowak has received research support from Alexion . The institution of Dr. Nowak has received research support from Janseen. The institution of Dr. Nowak has received research support from Immunovant . The institution of Dr. Nowak has received research support from argenx. The institution of Dr. Nowak has received research support from Amgen. Dr. Nowak has a non-compensated relationship as a Member of the Board of Directors with Myasthenia Gravis Foundation of America (MGFA) that is relevant to AAN interests or activities.
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.

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