Do Immunological Profiles of the Cerebrospinal Fluid Correlate with Disease Severity in Multiple Sclerosis? (P02.095)

Abstract

Objective: To determine if there is an immunological difference between benign and aggressive courses of multiple sclerosis (MS) by studying the immne cell composition of the cerebrospinal fluid. Background Demyelination of the Central Nervous System (CNS) caused by autoimmune inflammation is the hallmark of MS and results in various degrees of disease severity. We hypothesize that there may be immunological profiles that favor benign or aggressive MS courses. This would be important for our understanding of the pathogensis of disease severity and optimizing therapuetic strategies. Design/Methods: Patients were characterized as having Benign or Aggressive Multiple Sclerosis based on their rate of disease progression and activity since their diagnosis. We looked at a total of 40 patients with extremes of benign or aggressive disease including treated and untreated patients: 29-Aggressive and 11-Benign MS; 3-PPMS, 11-RRMS, and 26-SPMS. Following informed consent all participants donated peripheral blood (PB) and Cerebral Spinal fluid (CSF) for analysis. We analyzed leukocyte cell numbers as well as CD4+ Memory T cell subsets. Isolated cells were incubated in X-Vivo15 media with PMA (50ng/mL), Ionomycin (1μg/mL), and Brefeldin A (1X) for 5 hours at 37°C/5%CO2. Leukocytes were then stained for CD4, CD8, CD25, CD39, IL-4, IL-9, IL-10, IL-17A, IFNg, FoxP3, GM-CSF and analyzed by flow cytometry. Results: We found no differences in overall numbers of total cells or percentages of cell types found in the CSF. We did find an increase in IFNg-secreting cells in the CSF, PB, and CD4+ Memory T cells, of the untreated aggressive MS subgroup compared to benign MS. CSF: 53.9/16.7%, PB: 26.4/11.5%, CD4+ Memory T: 30.0/25%. Conclusions: Our results suggest that Th1-type IFNg-secreting T cells are dominant in aggressive disease. This may be part of an immune imbalance that leads to disease severity. Studies are ongoing to determine if there are other CSF immune differences in our study groups. Disclosure: Dr. Brydon has nothing to disclose. Dr. Marszal has nothing to disclose. Dr. Sadiq has nothing to disclose.