CD16+/Perforin+ Lymphocytes (NK Cells) May Regulate Autoimmunity in Multiple Sclerosis by Cytolysis of Antigen Laden Cells in the Peripheral Blood. (P1.162)

Abstract

OBJECTIVE: To determine whether a deficiency of perforin expressing NK cells in RRMS may underlie disease exacerbation BACKGROUND: NK Cells may play a regulatory role in Multiple Sclerosis in part perhaps by deleting antigen presenting cells and effector T-cells by cytotoxicity. The literature contains many studies describing a deficiency in NK Cell killing activity in Multiple Sclerosis and that transient dips in NK cell killing activity may precede symptomatic relapse. The molecular basis of the defect in killing activity has not been determined. DESIGN/METHODS: We studied the expression of Perforin in CD16+ Lymphocytes by flow cytometry of peripheral blood mononuclear cells (PBMCs). We also examined the presence of myelin loaded phagocytes in the circulation by ELISA in order to investigate the relationship between MBP in PBMC lysates and the % of CD16+ Lymphocytes expressing Perforin RESULTS: a relative deficiency in CD16+/Perforin+ Lymphocytes was found. A threshold level of CD16+/ Perforin+ Lymphocytes was found at 75%. Healthy controls (HC) had greater than 75% CD16+/Perforin+ Lymphocytes (10/11, 91%) in comparison with untreated MS (5/10, 50%) (Fisher’s exact test p= 0.05) and Glatirimer Acetate (GA) treated MS (15/18, 83%); HC vs GA p= 1.0, untreated vs GA p= 0.077. An inverse relationship between MBP in PBMC lysates and the % CD16+/ Perforin+ cells was found (r=0.77) CONCLUSIONS: An inverse relationship between MBP in PBMC lysates and the % CD16+/ Perforin+ cells is consistent with NK cell killing of antigen laden phagocytes in the periphery. An acquired defect in Perforin expression in CD16+ lymphocytes may play a role in the pathogenesis of MS through failure to delete antigen presenting cells and is potentially correctable with Glatirimer Acetate therapy. Study Supported by: MSDX Inc

Disclosure: Dr. Nayak has received personal compensation for activities with MSDx Inc as an employee. Mr. Jacolik has received personal compensation for activities with MSDx Inc.