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Abstract Details

Improved Accuracy in Myasthenia Gravis Using Combinatorial Algorithmic Autoantibody Testing
Autoimmune Neurology
S16 - Autoimmune Neurological Disorders: Diagnosis, Biomarkers, and Epidemiology (2:48 PM-3:00 PM)
010

To improve accuracy in diagnosis of MG using algorithmic acetylcholine receptor binding (ARBi) and modulating (ARMO) autoantibody testing beyond muscle-kinase (MusK) reflex testing

The diagnosis of myasthenia gravis (MG) is supported by clinical, electrophysiological and serological testing. 

Included consecutive Mayo Clinic patients suspected to have MG, over a 3 year period, having completed: 1) serologic testing for ARBi, ARMO and MusK Abs and; 2) electrophysiological testing. 

Among the 381 cohort, 33% (125) had MG as defined by myasthenic symptomatology and confirmatory electrophysiological testing (>10% decrement on 2-Hz repetitive stimulation or positive single fiber by Stahlberg-criteria). There were a total of 4 double negative MG patients (negative for ARBi and ARMO) of which 3 had ocular myasthenia and one had positive MusK. Best sensitivity (97%) for MG occurred by considering either ARBi > 0.02 nmol/L or ARMO >20% AchR loss. However, the clinical specificity of this approach was only 71%, translating to 74 patients with false positive results. Clinical specificity was significantly improved by requiring duel positivity of both binding and modulating assays (clinical specificity of 82%). This approach, however, reduced clinical sensitivity from 97% to 89%, because 8 MG patients who were ARBi positive are without ARMO positivity.  Next if we use an algorithmic approach whereby ARMO is only performed when ARBi is positive, the clinical performance will be unchanged (clinical sensitivity 89% and specificity 82%), and the number of ARMO tests performed will be reduced by >50%. Additionally there will be a 15% (55 to 47) reduction of false positive ARMO reported to physicians.  
Algorithmic combinatorial autoantibody testing improves accuracy for MG diagnosis.  By testing ARMO only in patients positive for ARBI, false positives for ARMO are significantly reduced.  Specificity should be emphasized in immunological testing to avoid unnecessary immunotherapy and thymectomy.
Authors/Disclosures
Shahar Shelly, MD (Rambam Medical Center)
PRESENTER 		Dr. Shelly has stock in Remepy.
Pritikanta Paul, MD (University of California, San Francisco) The institution of Dr. Paul has received research support from ZS Associates.
Hongyan Bi No disclosure on file
Divyanshu Dubey, MD, FAAN (Mayo Clinic) The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from UCB. Dr. Dubey has received research support from David J. Tomassoni ALS Research Grant Program . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care.
Eati Basal Eati Basal has nothing to disclose.
Sean J. Pittock, MD, FAAN (Mayo Clinic Dept of Neurology) Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arialys. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received publishing royalties from a publication relating to health care.
Anastasia Zekeridou, MD, PhD, FAAN (Neuroimmunology Laboratory, Mayo Clinic) The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care.
Andrew McKeon, MD (Mayo Clinic) The institution of Dr. McKeon has received research support from National Institutes of Health. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received publishing royalties from a publication relating to health care.
John R. Mills, MD, PhD (Mayo Clinic) The institution of Dr. Mills has received research support from Werfen Diagnostics. Dr. Mills has received intellectual property interests from a discovery or technology relating to health care.
Christopher J. Klein, MD, FAAN (Mayo Clinic) Dr. Klein has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Klein has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sangamo Therapeutics . Dr. Klein has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NMD Pharma.