Abstract Details

Title Evaluation of the Diagnostic Utility of Caveolae-associated Protein 4 (cavin-4) Epitope-based ELISA in Identification of Immune Mediated Rippling Muscle Disease

Topic Autoimmune Neurology

Presentation(s) S38 - Autoimmune Neurology: Peripheral Autoimmunity, Paraneoplastic Disease, Checkpoint Inhibitors, and Neurosarcoidosis (3:54 PM-4:06 PM)

Poster/Presentation
Number 003

Objective

To evaluate utility of caveolae-associated protein 4 (cavin-4) peptide enzyme-linked immunosorbent assay (ELISA) for detection of cavin-4 IgG among patients with immune-mediated rippling muscle disease (iRMD).

Background

iRMD is an autoimmune muscle disease associated with wave-like muscle rippling and percussion-/stretch-induced muscle mounding. Cavin-4-IgG is a novel autoantibody biomarker of iRMD discovered utilizing phage immunoprecipitation sequencing (PhIP-Seq). Peptide-based ELISA offers a high-throughput method to detect patient IgG targeting varying epitopes of cavin-4 in iRMD patients.

Design/Methods

Sera from iRMD patients evaluated at Mayo Clinic were tested on whole-human proteome PhIP-Seq to identify cavin-4 epitopes. Peptide-based ELISA and cavin-4-transfected HEK293 cell-based assay (CBA) were utilized for autoantigen confirmation.

Results

Nine patients (5 males) with archived sera within 1 year of iRMD diagnosis were identified (median age 53 [range 19-77] years). PhIP-Seq data revealed cavin-4 as the candidate autoantigen in all patients. Cavin-4 peptide 288-337 amino acid had one of the highest enrichment scores on whole human proteome PhIP-Seq in the majority of patients evaluated (56%). All nine patients were positive by cavin-4 288-337 amino acid peptide ELISA, while only seven of the nine patients were positive on cavin-4 CBA. Archived sera from healthy (CBA n=66, ELISA n=76) and disease controls (ELISA: hyper-gamma globulinemia [HGG], n=9; systemic lupus erythematosus, n=10; multiple sclerosis [MS], n=8; anti-mitochondrial antibody [AMA], n=12 and CBA: HGG, n=7; MS, n=8; AMA, n=12) tested uniformly negative. Clinical presentation of cavin-4 IgG seropositive patients included rippling of lower limb muscles (n=9), proximal weakness (n=4), and myalgia (n=9). All patients had percussion-induced muscle rippling and half had percussion- or stretch-induced muscle mounding. Only one of nine patients had underlying malignancy.

Conclusions

Cavin-4-IgG is a novel biomarker associated with immune-mediated rippling muscle disease. Our study highlights that cavin-4 epitope-based ELISA improves sensitivity without sacrificing specificity for cavin-4 IgG detection in iRMD.

Authors/Disclosures
Reghann LaFrance-Corey PRESENTER	Miss LaFrance-Corey has nothing to disclose.
Haidara Kherbek (Mayo Clinic)	Haidara Kherbek has nothing to disclose.
Margherita Milone, MD, FAAN (Mayo Clinic)	Dr. Milone has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Genetics, AAN. The institution of Dr. Milone has received research support from Mayo Clinic, CCaTS-CBD. The institution of Dr. Milone has received research support from Mayo Clinic, SGP Award. The institution of Dr. Milone has received research support from MDA for Care Center grant. The institution of Dr. Milone has received research support from Regenerative medicine Minnesota.
Pranjal Gupta, MD	Dr. Gupta has nothing to disclose.
Gregory Kraus (Mayo Clinic)	No disclosure on file
Teerin Liewluck, MD, FAAN (Department of Neurology, Mayo Clinic)	Dr. Liewluck has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta Therapeutics. Dr. Liewluck has received publishing royalties from a publication relating to health care.
William J. Litchy, MD, FAAN	Dr. Litchy 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.
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.
Andrew Knight	Andrew Knight has nothing to disclose.
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.

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