Search for Nodal and Paranodal Autoantibodies in Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) (P05.159)

Abstract

Objective: To examine whether in patients with CIDP there are antibodies against nodal and paranodal antigens such as contactin-2/TAG1, CASPR2 and neurofascin. Background Proteins physiologically expressed in the nodes of Ranvier may act as autoantigens in demyelination. Antibodies against contactin-2/TAG-1 (a protein that plays a role in the formation of axonal connections) have been detected in multiple sclerosis patients (Derfuss et al. PNAS 2009;106, 8302). Also, polymorphisms in the gene encoding TAG-1 influence treatment response in CIDP (Iijima et al. Neurology 2009;73, 1348). CASPR2, connexin-32, cadherin, neurofascin and ankyrin are all potential target antigens in PNS demyelination (Cifuentes-Diaz et al. Plos One 2011;6, e14533, Dalakas, Nat Rev Neurol 2011;7, 507). Design/Methods: We examined serum samples from 15 patients with autoimmune demyelinating neuropathy (13 with CIDP and 2 with multifocal motor neuropathy) and 9 disease controls (patients with Sjogren9s syndrome associated axonal polyneuropathy). We established a cell-based assay, in which human embryonic kidney cells were transfected with cDNA clones encoding either the FNIII, or the IgC2 domain of TAG-1 tagged with GFP. Serum antibody binding was visualized using an anti-human fluorescent secondary antibody. A monoclonal antibody against TAG-1 was used as a positive control. For nodal and myelin antigens commercially available assays were used. Results: No positive staining was detected in any of the 15 patients with autoimmune peripheral neuropathies in the contactin-2 assay. Results are pending for the other assays including experiments with IgG extracted from the patients9 sera. Conclusions: Anti-contactin-2 autoantibodies are not a marker for demyelination in CIDP and seems unlikely that contactin-2 is a candidate autoantigen. Reactivity to other nodal, paranodal or myelin antigens is currently explored and its relevance to CIDP will be reported. Supported by: Special Research Account, University of Athens. Disclosure: Dr. Pavlakis has nothing to disclose. Dr. Alexopoulos has nothing to disclose. Dr. Karagogeos has nothing to disclose. Dr. Dalakas has received personal compensation for activities with Baxter, Novartis, Grifols, Octapharma, and Therapath as a consultant and speaker.Dr. Dalakas has received research support from Genesis, Serono, and Novartis.