EBV, CMV, and HSV IgG Titers Are Not Predictive of Subsequent Relapse Risk in Pediatric Multiple Sclerosis (P02.096)

Abstract

Objective: We evaluated whether antibody response against Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus 1 and 2 (HSV) are associated with relapse rate in pediatric patients with multiple sclerosis (MS). Background Elevated EBV titers have been shown to be associated with having MS. Data conflict as to whether EBV response predicts disease activity or disease subtype. It is not known if viral antibody levels are associated with relapse rate. Design/Methods: Sera were collected early during disease course in patients who subsequently received prospective clinical follow-up to document relapses at 6 pediatric MS clinics. Antibodies against EBV early antigen (EBVEA, a marker of viral reactivation), Epstein-Barr nuclear antigen-1 (EBNA1), HSV, and CMV were measured by ELISA. A repeated events analysis was employed to determine if viral antibody response or status (positive vs. negative) predicted subsequent relapses. Proportional hazards models adjusted for the time-varying covariate of disease-modifying therapy usage and fixed demographic variables. Results: 111 participants had serum from initial visit and subsequent relapse data. The prevalence of positive status for EBVEA, EBNA1, CMV, HSV1, and HSV2 were, respectively, 44.1%, 89.2%, 24.3%, 38.7%, and 21.6%. There was no statistically significant association in the relapse hazard rate for EBVEA (hazard ratio (HR) 0.97, 95%CI:0.78 to 1.22, p=0.81) or for EBNA1 antibody response (HR 1.08, 95%CI: 0.71 to 1.65, p=0.7). Adjustment for disease-modifying therapy, race, ethnicity, gender and HLA-DRB1 status did not substantially affect HRs. Similarly, HRs for EBV status, CMV titer or status and HSV-1 or 2 titers or status, did not show an association with subsequent relapse rate. Conclusions: Although previous studies have shown an association between prior infection with EBV and risk of MS, we did not detect an association between EBV, CMV or HSV antibody response and subsequent relapse rate in pediatric MS patients. Supported by: Dr. Graves is supported by the National Multiple Sclerosis Society Sylvia Lawry Award. The work was funded by the Nancy Davis Foundation and the NMSS. Disclosure: Dr. Graves has nothing to disclose. Dr. Krupp has received personal compensation for activities with Teva Neuroscience, BiogenIdec, Serono, Inc., Bayer Pharmaceuticals Corporation, Guidepoint Global, Pfizer Inc, Axon Advisors, Sanofi-Aventis Pharmaceuticals, Inc., as a speaker, consultant and/or participant on an advisory board. Dr. Krupp has received (royalty or license fee or contractual rights) payments from Genzyme Corporation, Bristol-Myers Squibb Company, MedImmune, and Novartis. Dr. Krupp has received research support from Serono Inc. and Biogen Idec. Dr. Weinstock-Guttman has received personal compensation for activities with Acorda Therapeutics, Biogen Idec, Serono, Inc., Novartis, Pfizer Inc, Teva Neuroscience as a speaker and/or participant on an advisory board. Dr. Weinstock-Guttman has received research support from Acorda Therapeutics, Biogen Idec, Serono Inc., Novartis, Pfizer Inc, Teva Neuroscience, National Multiple Sclerosis Society, the National Institutes of Health, ITN, Teva Neuroscience, Aspreva-Roche, Acorda Therapeutics and Shire Pharmaceuticals. Dr. Strober has nothing to disclose. Dr. Belman has nothing to disclose. Dr. Yeh has nothing to disclose. Dr. Ness has received research support from EMD Serono. Dr. Gorman has nothing to disclose. Dr. Rodriguez has nothing to disclose. Dr. Chitnis has received personal compensation for activities with Teva Neuroscience, Biogen Idec, Sanofi-Aventis Pharmaceuticals, Inc., and Novartis. Dr. Chitnis has received research support from Merck Serono. Dr. Waubant has received personal compensation for activities with Teva Neuroscience, Actelion, Sanofi-Aventis Pharmaceuticals, Roche Diagnostics Corporation and Biogen Idec as a speaker and/or consultant. Dr. Waubant has received research support from Biogen Idec and Sanofi-Aventis Pharmaceuticals.