Abstract Details

Title Functional CD8+ T cell-specific Immune Response Alterations under Ocrelizumab Treatment

Topic Multiple Sclerosis

Presentation(s) MS and CNS Inflammatory Disease Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 199

Objective To investigate the viral CD8+ T cell cellular immune response under ocrelizumab.

Background Administration of higher efficacy disease modifying drugs in multiple sclerosis patients is not without concern during the SARS-CoV-2 pandemic. Under ocrelizumab, an anti-CD20 antibody that causes depletion of circulating B cells with minor alleged effect on T cells, infections are generally mild, although the risk of both viral and bacterial infection is slightly increased.

Design/Methods We performed repeated enzyme linked immunospot assays (ELISPOT) in a cohort of 37 ocrelizumab-treated MS patients, before treatment initiation (T0), and at 6 months (T6) and one year into treatment (T12). Viral antigens consisted in a pool of immunodominant 8-10 mer epitope peptides including epitopes of EBV, CMV, and Influenza. Further characterization of CD8+ T cell subtypes was done using mass cytometry. We corrected all data for age and total CD8+ T cell count using linear regression models.

Results Of the 37 patients tested, 27 had positive ELISPOT assays at T0 while only 21 remained positive at T12. Although the total number of CD8+ T cells remained stable (p=0.117), the frequency of IFN-gamma secreting CD8+ T cells, among the responders, was significantly reduced in 51.5% of patients at T6 (p=0.002) and 55.2% at T12 (p<0.001). Furthermore, at T6 and T12, subpopulation analysis revealed a 22.7% reduction in memory CD8+ T cell numbers as compared to T0 (p=0.003), mostly due to a depletion of CD8/CD20 double positive T cells (frequency reduced by 68.8%, p<0.001) and an increase in numbers of naïve CD8+ T cells (23.4%, p=0.004). No correlation was noted with age at disease onset (p=0.366) or with age at ocrelizumab onset (p=0.174).

Conclusions Although a minor component of the total pool of CD8+ T cells, the double positive CD8/CD20 T cells may play an important role in virus-specific cellular immune response.

Authors/Disclosures
Vasiliki Pantazou, MD (CHUV, Lausanne) PRESENTER	Dr. Pantazou has nothing to disclose.
Sylvain Perriot (CHUV)	Mr. Perriot has nothing to disclose.
	No disclosure on file
Marie Théaudin (Chuv)	The institution of Marie Théaudin has received research support from Pfizer. The institution of Marie Théaudin has received research support from Asrim.
	No disclosure on file
	No disclosure on file
Renaud A. Du Pasquier, MD, FAAN (Service of neurology, CHUV)	Dr. Du Pasquier has nothing to disclose.

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