Abstract Details

Title Naturally Occurring Anti-Neuronal Antibodies within IVIg Preparations: Importance in Clinical Practice

Topic Autoimmune Neurology

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-072

Objective To test for anti-neuronal antibodies within commercially available IVIg preparations.

Background

Intravenous immunoglobulin (IVIg) is an effective immunotherapy in various autoimmune neurological disorders. One mechanism of action is thought to be via idiotypic antibodies within the IVIg preparations.

Design/Methods Samples (n=16) from 5 different commercially available IVIg preparations were tested for: a) anti-aquaporin 4 (AQP4) antibodies with ELISA and Cell-Based-Assay (CBA); b) anti-myelin oligodendrocyte glycoprotein (MOG) antibodies with CBA; c) anti-Human 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGCR) antibodies with ELISA; d) anti-GAD antibodies with ELISA ; and e) antibodies against nodal or other neuronal autoantigens using immunohistochemistry on teased fibers from mouse sciatic nerve or brain sections.

Results Antibodies to AQP4 were detected by ELISA in 15/16 IVIg preparations (as determined by the manufacturer cut-off), with titers comparable to those seen in AQP4-seropositive control NMO patients; in contrast to NMO patients however, all IVIg samples were antibody-negative with CBA. Two IVIg preparations were positive for anti-HMGCR antibodies, at low titers. Anti-GAD antibodies were detected in 15/16 IVIg preparations, with titers ranging from 41-816 IU/ml, as typically seen in Type-I diabetes, but not in the range seen in GAD-positive neurological patients, like Stiff-Person Syndrome, where the titers are >2000 IU/ml. None of the IVIg preparations were MOG-positive or had anti-nodal or other neuronal autoantibodies based on lack of immunoreactivity on teased nerve fibers or brain sections.

Conclusions IVIg preparations contain antibodies against GAD and AQP4 in titers comparable to those seen in autoimmune patients. The neuronal antibodies within the IVIg are not however detected with CBA or tissue immunostaining suggesting that they are directed against linear, rather than structural epitopes, probably as part of the natural antibody immune repertoire. The information is clinically important for diagnosis when testing patients’ sera after they have received therapy with IVIg to avoid false interpretation.

Authors/Disclosures
Maria Dimitriadou PRESENTER	No disclosure on file
Harry Alexopoulos	No disclosure on file
Sofia Akrivou	No disclosure on file
	No disclosure on file
Marinos C. Dalakas, MD, FAAN (Thomas Jefferson University)	Dr. Dalakas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Grifols, . Dr. Dalakas has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Dysimmune Diseases Foundation. Dr. Dalakas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octapharma. Dr. Dalakas 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. Dalakas has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. Dr. Dalakas has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Therapeutic Advances in Neurology (TAND). Dr. Dalakas has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medlink.

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