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Abstract Details

Single Cell Analysis of MS CSF B-Cells Show Significant Differences in Expansion Patterns and Gene Family Usage Between MS Subtypes
Multiple Sclerosis
P4 - Poster Session 4 (5:30 PM-6:30 PM)
9-005

To characterize differences in B-cells clonal expansion across multiple sclerosis (MS) subtypes through single cell sequence analysis.

The presence of CSF IgG oligoclonal bands as a diagnostic marker and the effectiveness of B-cell targeted therapies suggest an essential role of B-cells in MS. However, their exact role in MS is unknown. Examining trends in B-cell clonal expansion and gene family usage may elucidate a mechanism of B-cells mediated MS. Our previous studies suggest differences in profiles and effects of PPMS, RRMS, and SPMS derived CSF. Analysis of single cell data offers novel insight into these patterns.

CSF cells from MS patients were stained for CD19 and CD138 and sorted via FACS. Nested PCRs amplified the variable region and a small portion of the constant region. Sequence analysis identified the gene family and cell expansion. We applied advanced algorithm-driven analysis to discover patterns in the dataset. These findings were verified using FACS data for untreated patients with minimum 9 cells sequenced.
B-cells were significantly more expanded in PPMS compared to other subtypes. In PPMS, 16.82% of sequenced unique cells were expanded whereas only 8.86% were expanded in RRMS and 4.15% in SPMS. Interestingly, although SPMS had the fewest expanded clones, these expanded clones were more numerous than average PPMS or RRMS expansion counts. Additionally, the gene family IGHV4 was upregulated in MS, as reported by other labs. Our data suggests this increase is primarily from RRMS, where IGHV4 frequency is 41% compared to the expected 20.4%. IGHV4 was upregulated in PPMS and SPMS, but to a lesser extent. Expanded cells also preferred IGHV4. 7.6%, 5.6%, 7.8%, and 9.6% of expanded cells expressed IGHV1, IGHV2, IGHV3, and IGHV4, respectively. 
This data suggests fundamentally different roles of B-cells among MS subtypes. Future investigations will clarify pathogenic roles of these differences in CSF profiles.
Authors/Disclosures

PRESENTER 		No disclosure on file
Francesca M. Cali (Tisch MS Research Center of New York) No disclosure on file
Jerry Lin, BS (Tisch Multiple Sclerosis Research Center of NY) Mr. Lin has nothing to disclose.
Saud Sadiq, BS, FÂ鶹´«Ã½Ó³»­ (Tisch Multiple Sclerosis Research Center of New York) Ms. Brewi has nothing to disclose.