Abstract Details

Title Antibodies to Contactin-1 in Chronic Inflammatory Demyelinating Polyneuropathy

Topic Peripheral Nerve

Presentation(s) P01 - (-)

Poster/Presentation
Number 150

Objective

Background BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a disorder that includes patients with variable phenotypes and different responses to treatment. Its pathogenesis is autoimmune, with probable involvement of autoantibodies. Previous reports describe antibodies against myelin and axonal proteins, but their pathogenicity is controversial. Recent studies highlight the importance of the axo-glial junction in CIDP pathogenesis. Contactin-1 (CNTN1) and contactin associated protein 1 (CASPR1) are proteins of paranodes that play an essential role in myelination. We describe the presence of antibodies against CNTN1 and CNTN1/CASPR1 complex in a small subset of CIDP patients sharing specific clinical features.

Design/Methods DESIGN/METHODS: We designed an unbiased approach for antigen unraveling using patients' sera for hippocampal neuron immunoprecipitation. Mass spectrometry analysis revealed CNTN1-complex proteins in the precipitate. The presence of antibodies against CNTN1 complex was confirmed by immunocytochemistry in CNTN1-transfected cells, sciatic nerve immunohistochemistry and inhibition experiments. Patients' clinical features and response to therapy were reviewed.

Results RESULTS: Forty-six patients were included in the study. Two patients' sera have antibodies against CNTN1 protein. Another patient precipitated both CNTN1 and CASPR1 proteins and had antibodies against the CNTN1/CASPR1 complex. All three patients shared clinical features including late and, aggressive onset, predominantly motor involvement with early axonal damage and poor response to intravenous immunoglobulins. CNTN1 antibodies were absent in 14 healthy controls and 90 patients with other neurological diseases, including 48 patients with Guillain-Barre syndrome.

Conclusions CONCLUSIONS: We describe the presence of antibodies against CNTN1-complex in a small subset of CIDP patients with homogeneous clinical features and response to therapy. Those antibodies could provide a diagnostic and prognostic biomarker. Studies with similar design can help discovering other autoantibodies and defining prognostic subgroups in CIDP. This work has been accepted for publication in Annals of Neurology.

Authors/Disclosures
Isabel Illa, MD (Hospital Sant Pau) PRESENTER	No disclosure on file
Gisela Nogales-Gadea	No disclosure on file
Luis Querol, MD, PhD (Hospital de la Santa Creu i Sant Pau)	Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL Behring. The institution of Dr. Querol has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB. Dr. Querol has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ArgenX. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dianthus. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Annexon. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avilar. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocryst. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for KPL. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lycia. The institution of Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Querol has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Querol has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Querol has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. The institution of Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ArgenX. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Grifols. The institution of Dr. Querol has received research support from GBS-CIDP Foundation International. The institution of Dr. Querol has received research support from Grifols. The institution of Dr. Querol has received research support from ISCIII. The institution of Dr. Querol has received research support from CIBERER. The institution of Dr. Querol has received research support from UCB. The institution of Dr. Querol has received research support from ArgenX.
Francesco Patti, MD	Dr. Patti has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Patti has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Almirall. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Meyers. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson and Johnson. The institution of Dr. Patti has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck. The institution of Dr. Patti has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Patti has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. The institution of Dr. Patti has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Almirall, Bayer, Biogen, Bristol Meyers and Squibb Merck, Roche, Sanofi, TEVA. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for University of Catania and AISM/FISM, Fondazione Italiana Sclerosi Multipla. Dr. Patti has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology.
Eduard Gallardo	No disclosure on file
	No disclosure on file

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