Abstract Details

Title Identification of Responders to Glatiramer Acetate in MS with Antigen Arrays

Topic MS and Related Diseases

Presentation(s) S11 - (-)

Poster/Presentation
Number 002

Objective

Background Using antigen arrays we have found serum antibody signatures associated to different stages of MS, pathology and MRI. In this study we asked whether serum antibody patterns were associated with the response to GA in MS.

Design/Methods Antigen microarrays consist of 420 antigens including CNS-related autoantigens, lipids, virus-derived antigens and other autoantigens. We analyzed serum samples from GA-treated MS patients classified as responders (R) or non-responders (NR) based on strict clinical criteria. We analyzed: 1) Samples taken before the initiation of GA therapy, from R or NR MS patients (n=18/group) 2) Samples obtained 6-12 months after the initiation of therapy (n=49 and 50 for NR and R, respectively); 30 Samples obtained 18-24 months after the initiation of therapy (n=36 and 39 for NR and R, respectively). In each of these sets, 2/3 of the samples were used as a "training set" to identify antibody signatures associated with treatment response , and 1/3 was used as a "test set" to validate the signatures.

Results We found IgG antibody patterns associated with a beneficial clinical response in samples taken 6-12 months after the initiation of GA-therapy and in comparison of longitudinal samples taken before and 6-12 months after GA therapy. Response was linked to a decrease in myelin reactivity after therapy. A support vector machine constructed on the basis of the differential antibody reactivities identified responders to GA therapy with an area under the curve in an ROC analysis >70% in the test set.

Conclusions Our data suggests that serum antibody repertoires are potential biomarkers for prediction and early detection of response to GA.

Authors/Disclosures
Francisco J. Quintana, PhD (Brigham and Women's Hospital/Harvard Medical) PRESENTER	Dr. Quintana has nothing to disclose.
	No disclosure on file
Taha Gholipour, MD (UC San Diego Health - Comprehensive Epilepsy Center)	Dr. Gholipour has nothing to disclose.
Samia J. Khoury, MD, FAAN (Nehme and Therese Tohme MS Center)	Dr. Khoury has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merk. Dr. Khoury has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Khoury has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for ANA. Dr. Khoury has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Clinical Immunology. The institution of Dr. Khoury has received research support from MENACTRIMS. The institution of Dr. Khoury has received research support from NMSS. The institution of Dr. Khoury has received research support from Office of Naval Research USA. An immediate family member of Dr. Khoury has received intellectual property interests from a discovery or technology relating to health care.
Tanuja Chitnis, MD, FAAN (Brigham and Women's Hospital)	Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche-Genentech. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Siemens. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave Biosciences. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. The institution of Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Academic CME. The institution of Dr. Chitnis has received research support from Novartis. The institution of Dr. Chitnis has received research support from Sanofi. The institution of Dr. Chitnis has received research support from Octave. The institution of Dr. Chitnis has received research support from Genentech-Roche. The institution of Dr. Chitnis has received research support from Tiziana Life Sciences. The institution of Dr. Chitnis has received research support from Bristol-Myers Squibb. The institution of Dr. Chitnis has received research support from Wesley Clover.
Roopali Gandhi, PhD (Sanofi Genzyme)	No disclosure on file
	No disclosure on file
Howard L. Weiner, MD (Brigham and Women'S Hospital)	Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for vTv Therapeutics. Dr. Weiner has stock in vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc..
Steven Galetta, MD, FAAN (NYU Langone Medical Center)	Dr. Galetta has nothing to disclose.

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