Abstract
Objective: The aim of this study was to analyze whether serum antibody patterns detected with antigen arrays distinguish pediatric MS (pMS)from monophasic acute demyelinating syndrome (mADS). Background Using antigen arrays we have found serum antibody signatures associated to different stages of MS and also to different pathological processes. In the present study we investigated serum antibody patterns in pMS and mADS samples. Design/Methods: Antigen microarrays consisted of 420 antigens including CNS-related autoantigens, lipids, virus-derived antigens and other autoantigens. We analyzed the following sets of samples: 1. Pediatric samples obtained during an acute demyelinating attack (pMS n=34 and mADS n=34). 2. Pediatric samples obtained 3 months after an acute demyelinating attack (convalescence samples, pMS n=28 and mADS n=34). In each of these sets, 2/3 of the samples were used as a “training set” to identify antibody signatures associated to each group, and 1/3 was used as a “test set” to validate the antibody signatures. Finally, an independent validation cohort of pediatric samples taken 3 months after an acute demyelinating attack (pMS n=11 and mADS n=11) was used to validate the antibody signature associated with the convalescence samples. Results: We found antibody patterns significantly associated with pMS both in samples obtained during an acute demyelinating attack and 3 months after an acute demyelinating attack; convalescence pMS samples showed a significant increase in antibody reactivity against CNS antigens. Moreover, a support vector machine constructed on the basis of the differential antibody reactivities identified in the convalescence phase identified pMS samples with an area under the curve in an ROC analysis >80% in the test set and >75% in the validation cohorts, respectively, of convalescence samples. Conclusions: Our data suggests that serum antibody repertoires detected with antigen arrays are potential biomarkers for predicting the future development of MS in pediatric patients. Supported by: EMD Serono and National MS Society. Disclosure: Dr. Quintana has received personal compensation for activities with EMD Serono and Teva Neuroscience as a consultant and/or speaker. Dr. Quintana has received research support from EMD Serono. Dr. Rahbari has nothing to disclose. Dr. Magalhaes has nothing to disclose. Dr. McGowan has nothing to disclose. Dr. Johnson has nothing to disclose. Dr. Rajasekharan has nothing to disclose. Dr. Weiner has received personal compensation for activities with Biogen Idec, Novartis, Serono, Inc., Teva Neurosciences, GlaxoSmithKline, Nasvax, Xenoport and Genzyme Corporation as consulting and/or speaking activities. Dr. Weiner has received research support from Merck Serono. Dr. Banwell has received personal compensation for activities with Merck-Serono, Biogen-IDEC, Bayer Pharmaceuticals Corporation, Genzyme Corporation and Teva Neuroscience as a speaker and or advisor. Dr. Bar-Or has received personal compensation for activities with Aventis Pharmaceuticals, Bayhill Therapeutics, Biogen Idec, Berlex Laboratories, Eli Lilly & Company, Genentech, Inc., GlaxoSmithKline, Ono Pharmaceutical, Diogenix, Roche Diagnostics Corporation, Merck Serono, Novartis, Teva Neuroscience.
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