Abstract Details

Title A Mathematical Analysis of Neural Autoantibody Clusters Encountered in Sera of 78,889 Patients Undergoing Comprehensive Paraneoplastic Autoantibody Evaluation

Topic Neurotoxicology

Presentation(s) S29 - (-)

Poster/Presentation
Number 006

Objective

Background Autoantibodies against onconeural antigens commonly coexist. They reflect a multifaceted immune response against a definable cancer. We present a mathematical analysis of neural autoantibody coexistence.

Design/Methods We analyzed results for a standardized neural autoantibody evaluation performed in the Mayo Clinic Neuroimmunology Laboratory (2008-2011) on sera from 78,889 patients. The 1.2 million tests included antibodies specific for intracellular autoantigens (neuronal nuclear proteins {ANNA-1/anti-Hu, ANNA-2/anti-Ri and ANNA-3}; glial nuclear proteins {AGNA/SOX1}; neuronal cytoplasmic proteins {PCA-1/anti-Yo, PCA-2, PCA-Tr, amphiphysin, CRMP-5} and muscle cytoplasmic proteins: striational {Str}) and plasma membrane autoantigens (neuronal voltage-gated-channels: Kv1.1 potassium channel-complexes {VGKC}and calcium channels {VGCC-N and VGCC-P/Q}; and nicotinic acetylcholine receptors {AChRs}: ganglionic {g} and muscle {m} types). The frequencies of antibody clusters observed were compared to hypothesized frequencies (i.e., anticipated by chance).

Results At least one neural autoantibody was detected in 9182 patients (11.6%). Observed cluster frequencies exceeding hypothesized included: mAChR with Str (535 vs 46); VGCC-N with VGCC-P/Q (150 vs 6); VGKC with Str (129 vs 67); mAChR with Str and gAChR (84 vs 1); mAChR with Str and VGKC (20 vs 2); VGKC with VGCC-N and VGCC-P/Q (18 vs 0); Str with VGCC-N and VGCC-P/Q (13 vs 0); mAChR with Str and CRMP-5 (7 vs 0); VGKC with Str andVGCC-P/Q (6 vs 1); mAChR with VGCC-N and VGCC-P/Q (6 vs 0); ANNA-1 with VGCC-N and VGCC-P/Q (5 vs 0); AGNA/SOX1 withVGCC-N and VGCC-P/Q (5 vs 0). Cluster-specific demographic, oncologic and neurological differences emerged.

Conclusions The clustering of onconeural antibodies implicates multimolecular tumor-derived antigenic complexes both as initiators and neural targets of paraneoplastic immune responses. Autoantibody profiles are a measurable immunobiological outcome of cancer and aid both neurological and oncologic diagnosis.

Authors/Disclosures
Erika S. Horta, MD (University of Arkansas Medical School) PRESENTER	Dr. Horta has nothing to disclose.
	No disclosure on file
	No disclosure on file
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.
Vanda Lennon, MD, PhD (Mayo Clinic)	The institution of Dr. Lennon has received research support from NIH. Dr. Lennon has received intellectual property interests from a discovery or technology relating to health care.
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.
Richard S. Nicholas, FRCP (Imperial College Healthcare Trust)	Dr. Nicholas has nothing to disclose.

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