Abstract Details

Title Anti-Neuronal Nuclear Antibody 3 Autoimmunity targets Dachshund homolog 1

Topic Autoimmune Neurology

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 013

Objective To identify the autoantigen defined by Anti-Neuronal Nuclear Antibody-type 3 (ANNA3)-IgG and describe the clinical phenotype of seropositive patients.

Background

ANNA3 was described in 11 patients with multifocal neurological presentations and cancer; its detection is based on the characteristic immunofluorescence staining on mouse tissue sections; ignorance of the antigen’s molecular identity has precluded its ready detection in clinical practice.

Design/Methods This study was performed at the Mayo Clinic Neuroimmunology Laboratory. The ANNA3-IgG antigen, identified by immunoprecipitation and mass spectrometry as Dachshund-homolog 1 (DACH1), was confirmed by using a commercial DACH1-specific IgG for immunohistochemical colocalization, antigen-specific Western blot, transfected cell-based immunofluorescence, and immune absorption experiments. Clinical data were abstracted from patients’ medical records or provided by referring physicians.

Results IgG in 32 ANNA3 seropositive patient sera, but in none of 145 controls, bound to DACH1. Clinical information was available for 30 patients (median age, 63.5 years [range, 49-88]; 67% female). Neurological manifestations included neuropathy, 12; cognitive difficulties or encephalitis, 11; ataxia, 8; dysautonomia, 7 (two additionally had diarrhea and esophageal spasm); chorioretinopathy, 1. Clinical improvement was noted in 8 of 11, all treated with immunosuppressants or oncologic treatment. In two patients, the neurological syndrome appeared or worsened during immune checkpoint inhibitor cancer immunotherapy. A neoplasm was found in 27 patients (90%); fourteen were of neuroendocrine lineage. Coexisting neural autoantibodies were detected in 14 patients (47%), and most predicted a neuroendocrine tumor (specific for neuronal intermediate filaments, collapsin response-mediator protein-5, voltage-gated calcium channel [P/Q-type], ANNA1, SOX1, Purkinje-cell cytoplasmic autoantibody type 2/microtubule-associated-protein-1B).

Conclusions IgG specific for DACH1 is a serological biomarker of neurological autoimmunity and cancer in patients of middle-age or older. DACH1-IgG is a valuable addition to comprehensive autoimmune and paraneoplastic neural antibody evaluations in clinical practice.

Authors/Disclosures
Anastasia Zekeridou, MD, PhD, FAAN (Neuroimmunology Laboratory, Mayo Clinic) PRESENTER	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.
Binxia Yang (Mayo clinic)	Binxia Yang has nothing to disclose.
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.
Yong Guo	Yong Guo has nothing to disclose.
	No disclosure on file
Claudia F. Lucchinetti, MD, FAAN (University of De Medical School, Health Learning Blg)	The institution of Dr. Lucchinetti has received research support from Biogen Idec. The institution of Dr. Lucchinetti has received research support from NIH/NINDS. The institution of Dr. Lucchinetti has received research support from National Institute of Neurological Disorders and Stroke . The institution of Dr. Lucchinetti has received research support from National Multiple Sclerosis Society. The institution of Dr. Lucchinetti has received research support from National Center for Advancing Translational Sciences. Dr. Lucchinetti has received intellectual property interests from a discovery or technology relating to health care. Dr. Lucchinetti has a non-compensated relationship as a Member with National Institute of Neurological Disorders that is relevant to AAN interests or activities. Dr. Lucchinetti has a non-compensated relationship as a Member with Board of Directors, Association of University Professors of Neurology that is relevant to AAN interests or activities. Dr. Lucchinetti has a non-compensated relationship as a Member with Mayo Clinic Board of Trustees that is relevant to AAN interests or activities. Dr. Lucchinetti has a non-compensated relationship as a Member with Mayo Clinic Board of Governors that is relevant to AAN interests or activities.
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.
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 Arialys. 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. 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. 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.
Eoin P. Flanagan, MBBCh, FAAN (Mayo Clinic)	The institution of Dr. Flanagan has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for UCB. The institution of Dr. Flanagan has received research support from UCB. The institution of Dr. Flanagan has received research support from Roche. The institution of Dr. Flanagan has received research support from UCB. The institution of Dr. Flanagan has received research support from Merck. The institution of Dr. Flanagan has received research support from Roche. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial Board Member with Neurology, Neuroimmunology Neuroinflammation (N2) Journal that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial Board Member with Neurology that is relevant to AAN interests or activities.

��ɫ��

��ɫ��