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Abstract Details

Investigating Autoantibody Profiles in Seronegative Myasthenia Gravis
Autoimmune Neurology
P1 - Poster Session 1 (8:00 AM-9:00 AM)
6-005

MG is characterized by a detrimental humoral response against key proteins on the neuromuscular junction, including the acetylcholine receptor (AChR) and muscle-specific tyrosine kinase (MuSK). In about 10% of MG patients, defined as seronegative, a lack of detectable autoantibodies by radioimmunoassay hampers a prompt diagnosis and restricts eligibility for clinical trials and payers’ reimbursement for certain therapies. In variable proportions of SNMG patients, autoantibodies can be detected by cell-based assays (CBA). However, data on CBA positivity rates in the U.S. are lacking. Moreover, the prevalence of low-density lipoprotein receptor-related protein 4 (LRP4) autoantibodies, and the presence of autoantibodies against yet unidentified muscle autoantigens, remain uncertain in SNMG.

To refine the serological characterization of patients with seronegative myasthenia gravis (SNMG) and explore novel disease-specific autoantibody reactivities.
Serum or plasma samples from SNMG patients in two U.S. academic centers were tested by clustered AChR, MuSK or LRP4 CBA using flow cytometry. A B cell culturing approach that allows for in vitro differentiation of B cells into antibody-secreting cells was employed to identify circulating antigen-specific B cells and generate recombinant monoclonal antibodies. Rapid extracellular antigen profiling (REAP), a high-throughput antibody discovery technique, was leveraged to explore novel autoantibody reactivities in SNMG patients.

Of 99 SNMG samples tested by CBA, 18 (18.2%) were positive for AChR autoantibodies; none were MuSK or LRP4 autoantibody positive. As further evidence of a positive AChR autoantibody status, circulating AChR-specific B cells were identified in a CBA-positive SNMG patient, and their specificity was validated through the isolation of a recombinant monoclonal antibody. REAP revealed potentially novel autoantibody reactivities restricted to SNMG patients.

Findings from a large SNMG cohort support the clinical need to implement clustered AChR CBA testing in the evaluation of SNMG patients. Further ongoing investigations are warranted to confirm the presence of novel autoantibodies in SNMG.
Authors/Disclosures
Gianvito Masi, MD (Yale University)
PRESENTER
Dr. Masi has nothing to disclose.
Minh C. Pham (Yale University) Mr. Pham has nothing to disclose.
No disclosure on file
Yingkai Li, MD, PhD (Duke University) Dr. Li has nothing to disclose.
Tabitha Karatz (Duke University) No disclosure on file
Seneca Oxendine Ms. Oxendine has nothing to disclose.
Vern C. Juel, MD, FAAN (Duke University Medical Center) Dr. Juel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunovant. Dr. Juel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Juel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Accordant Health Services. Dr. Juel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. The institution of Dr. Juel has received research support from argenx. The institution of Dr. Juel has received research support from Alexion. The institution of Dr. Juel has received research support from Janssen. The institution of Dr. Juel has received research support from NIH Rare Diseases Network.
No disclosure on file
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 Momenta . Dr. Nowak has received personal compensation in the range of $500-$4,999 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 $500-$4,999 for serving as a Consultant for Viela Bio. Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cour Pharma. The institution of Dr. Nowak has received research support from Ra Pharma. The institution of Dr. Nowak has received research support from Alexion . The institution of Dr. Nowak has received research support from Momenta . The institution of Dr. Nowak has received research support from Immunovant . Dr. Nowak has received research support from argenx. Dr. Nowak has received research support from Viela Bio . 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.
Jeff Guptill, MD, FAAN (argenx US) Dr. Guptill has received personal compensation for serving as an employee of argenx. Dr. Guptill has stock in argenx.
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.