Autoimmune neurologic diseases
Objectives: We tested the hypothesis that SPMS has a different immunological and gene expression profile than benign MS.
Background: In contrast to SPMS, BMS is diagnosed primarily retrospective and weighted towards motor progression, specifically an Expanded Disability Status Scale (EDSS) £3 after at least 15 years of disease onset. Utilizing phase III EXPAND trial cohort of SPMS baseline blood samples, our study aims to identify immunological and gene expression changes between SPMS and BMS.
Methods: We conducted experiments with flow cytometry, mircroarray, luminex, and CyTOF comparing 40 SPMS patients to 20 age, sex, and disease duration matched BMS. We also used RRMS and HC. State-of-the-art CyTOF technology allowed the identification additional immune subsets changes.
Results: We found that 1) RRMS and SPMS has a significantly higher % of CD8+ T cells and higher % of B cells as compared to BMS. SPMS have significantly lower % of Th2 compared to HC. 2) Microarray analysis indicate that SPMS has a different gene expression profile than BMS; many of which are involved in immune response including both T and B cell mediated immunity. 3) B cell and myeloid cell dysregulation is a feature of RRMS and SPMS; 4) Elevation of sCD40L was found only in plasma of SPMS, but not in BMS nor RRMS.
Conclusion: SPMS has a different immunological and gene expression profile than BMS. Future longitudinal studies will allow us to determine immunological and gene expression changes which ultimately lead to discovery of new therapeutic targets for disease progression.