Humoral Responses to Systemic and Organ Specific Auto-Antigens in Multiple Sclerosis (P4.010)

OBJECTIVE: In this study, we survey the frequencies of auto-reactive antibody responses to endogenous disease-associated antigens in healthy controls (HC), relapsing and progressive MS and to assess their associations with clinical and MRI measures of MS disease progression. BACKGROUND: Neurodegeneration in Multiple Sclerosis (MS) is driven by complex molecular mechanisms involving cellular and humoral immune histotoxicity in combination with altered metabolic and intracellular processes. DESIGN/METHODS: 969 serum samples from 315 healthy controls (HC), 411 relapsing remitting MS (RR-MS), 128 secondary progressive MS (SP-MS), 33 primary progressive MS (PP-MS) and 82 patients with other neurological diseases for autoantibodies against two putative MS antigens CSF114, KIR4.1 a and b peptides and 26 key auto-antigens linked to systemic and organ specific autoimmune diseases using ELISA or LIA (Line Immunoassay). Associations with disability and MRI measures of lesional injury and neurodegeneration were also assessed. RESULTS: The frequencies of anti-KIR4.1a and anti-KIR4.1b IgG positivity were 9.8[percnt] and 11.4[percnt] in HC compared to 4.9[percnt] and 7.5[percnt] in RR-MS, 8.6[percnt] for both peptides in SP-MS and 6.1[percnt] for both peptides in PP-MS (p = 0.13 for KIR4.1a and p = 0.34 for KIR4.1b), respectively. These putative MS antibodies were not associated with MS compared to HC, or with MS disease progression. HLA DRB1*1501 positivity and anti- Epstein Barr virus antibodies, which are MS risk factors, were not associated with these putative MS antibodies. CONCLUSIONS: Antibody responses to KIR4.1a and KIR4.1b peptides are not increased in MS compared to HC nor associated with MS disease progression. The frequencies of the diverse auto-antibodies investigated are similar in MS and HC. Study Supported by: Immco Diagnostics Inc.,Buffalo, NY 14228 Disclosure: Dr. Malyavantham has received personal compensation for activities with IMMCO Diagnostics Inc. as an employee. Dr. Weinstock-Guttman has received personal compensation for activities with Biogen Idec, Teva Neuroscience, EMD Serono, Pfizer Inc., Novartis, Genzyme Corporation, Sanofi-Aventis Pharmaceuticals, Inc., Mylan, and Acorda Therapeutics. Dr. Weinstock-Guttma Dr. Suresh has received personal compensation for activities with Immco Diagnostics as an employee. Dr. Zivadinov has received personal compensation for activities with Teva Neuroscience, Biogen Idec, EMD Serono, Novartis, Claret Medical Inc., and Genzyme Corporation as a speaker and/or consultant. Dr. Shanahan has received personal compensation for activities with Immco Diagnostics as an employee. Dr. Badgett has nothing to disclose. Dr. Ramanathan has received personal compensation in an editorial capacity for The AAPS Journal.