How does ocrelizumab work…It depletes T cells some people say
If depletes B cells other peoples say
But is it because it gets rid of EBV responsive cells
The hypothesis being examined was that EBV infection causes MS through molecular mimicry. EBV is never eliminated following the initial infection, and the latent virus reactivates often enough to maintain a vigorous cellular and antibody response. It is suggested that the anti-EBV immune response cross-reacts with a brain antigen in people with MS.
Thus, the persistent and recurrent viral infection would drive a relapsingor progressive autoimmune disease. We suggest that B cell depletion with OCR substantially reduces the EBV viral load and removes the driving stimulus for the cross-reactive autoimmune response.
If OCR decreases the EBV antigenic stimulus to the immune system, then it was predicted that the anti-EBV immune response should decrease over time in patients treated with OCR.
Pham HPT, Gupta R, Lindsey JW. The cellular immune response against Epstein-Barr virus decreases during ocrelizumab treatment. Mult Scler Relat Disord. 2021 Sep 28;56:103282. doi: 10.1016/j.msard.2021.103282.
Background: Epstein-Barr Virus (EBV) is strongly associated with multiple sclerosis (MS). After initial infection, EBV maintains a life-long latent infection in B lymphocytes. Depletion of B lymphocytes from the blood with the anti-CD20 antibody ocrelizumab markedly reduces disease activity in MS. Our objective was to measure the effect of ocrelizumab treatment on the cellular immune response to EBV.
Methods: Blood was collected from MS patients before and during ocrelizumab treatment. Peripheral blood mononuclear cells were stimulated with various antigens, and the response was measured using tritiated thymidine for proliferation and ELIspot for number of interferon-γ producing cells.
Results: The proliferation to autologous EBV-infected cells (LCL) was decreased after both 6 and 12 months of treatment. The number of interferon-γ producing cells on ELIspot in response to stimulation with either LCL or EBV also decreased. Responses to varicella zoster virus, influenza virus, and a mitogen did not change significantly.
Conclusion: The cellular immune response to EBV and LCL decreases during treatment with ocrelizumab. The benefit of ocrelizumab for MS may be through removal of EBV antigenic stimulus.