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Research
Massive Restrain of Cytotoxic B cells in the Peripheral Blood During Fingolimod and Natalizumab Treatments in Multiple Sclerosis Patients
Vinícius de Oliveira Boldrini
Universidade Estadual de Campinas
Corresponding Author
ORCiD: https://orcid.org/0000-0003-3984-2689
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Recently, the success of anti-CD20 monoclonal antibody therapy brought a new light over the role of B cells in multiple sclerosis (MS) pathogenesis. Due to the expression pattern of CD20 during B cells ontogeny, this role seems to be extended beyond the antibodies' production and secretion. Therefore, here we investigated whether not only classical cytotoxic CD8+ T lymphocytes but also non-classical cytotoxic B cells may occur in the peripheral blood from relapsing-remitting MS (RRMS) patients.
Methods
104 RRMS patients during different treatment and 58 healthy donors were studied. CD19, GzmB, Runx3 and CD49d expression was assessed by flow cytometry analyses.
Results
Patients treated with Natalizumab (NTZ) showed an increased percentage of CD8+GzmB+ when compared to other MS therapies, untreated RRMS patients and healthy volunteers. Similarly, and unexpected, massive cytotoxic behavior of B cells CD19+GzmB+ was observed in RRMS patients during Fingolimod (FTY) and NTZ therapies when compared to Glatiramer, Interferonβ, untreated MS patients and healthy donors.
Conclusions
During different MS treatments, B cells exhibit cytotoxic behavior resembling CD8+ T lymphocytes. This data suggest a possible involvement of “cytotoxic” B cells during MS pathology. Monitoring cytotoxic subsets might become an available marker for the risk of relapses and even for accessing therapeutic effectiveness in MS patients.
Keywords
Cytotoxicity, Granzyme B, Neuroinflammation, Neurodegeneration, MS treatments
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This is a preprint. It has not completed peer review.
Research
Massive Restrain of Cytotoxic B cells in the Peripheral Blood During Fingolimod and Natalizumab Treatments in Multiple Sclerosis Patients
Vinícius de Oliveira Boldrini
Universidade Estadual de Campinas
Corresponding Author
ORCiD: https://orcid.org/0000-0003-3984-2689
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 02 Jun, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurobiology of Disease
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Recently, the success of anti-CD20 monoclonal antibody therapy brought a new light over the role of B cells in multiple sclerosis (MS) pathogenesis. Due to the expression pattern of CD20 during B cells ontogeny, this role seems to be extended beyond the antibodies' production and secretion. Therefore, here we investigated whether not only classical cytotoxic CD8+ T lymphocytes but also non-classical cytotoxic B cells may occur in the peripheral blood from relapsing-remitting MS (RRMS) patients.
Methods
104 RRMS patients during different treatment and 58 healthy donors were studied. CD19, GzmB, Runx3 and CD49d expression was assessed by flow cytometry analyses.
Results
Patients treated with Natalizumab (NTZ) showed an increased percentage of CD8+GzmB+ when compared to other MS therapies, untreated RRMS patients and healthy volunteers. Similarly, and unexpected, massive cytotoxic behavior of B cells CD19+GzmB+ was observed in RRMS patients during Fingolimod (FTY) and NTZ therapies when compared to Glatiramer, Interferonβ, untreated MS patients and healthy donors.
Conclusions
During different MS treatments, B cells exhibit cytotoxic behavior resembling CD8+ T lymphocytes. This data suggest a possible involvement of “cytotoxic” B cells during MS pathology. Monitoring cytotoxic subsets might become an available marker for the risk of relapses and even for accessing therapeutic effectiveness in MS patients.
Figure 1
Figure 2
Figure 3