Direct, indirect and longitudinal immunological effects of anti-CD20 mediated B cell depletion in Multiple Sclerosis

by Nitzan Nissimov
Doctoral thesis
Date of Examination:2021-08-19
Date of issue:2021-08-10
Advisor:Prof. Dr. Martin Weber
Referee:PD Dr. Fred Lühder
Referee:Prof. Dr. Jürgen Wienands
Persistent Address: http://dx.doi.org/10.53846/goediss-8779

 

 

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Abstract

English

B cell depletion via anti-CD20 antibodies is a highly effective treatment for multiple sclerosis (MS). However, little is known about the maturation/activation stage of the returning B cell population after treatment cessation and the wider effects on other immune cells. In the present study, 15 relapsing-remitting MS patients receiving 1,000 mg of rituximab were included. B, T, and myeloid cells were analyzed before anti-CD20 administration and in different time intervals thereafter over a period of 24 mo. In comparison to the phenotype before anti-CD20 treatment, the reappearing B cell pool revealed a less mature and more activated phenotype: 1) reappearing B cells were significantly enriched in transitional and mature naive phenotypes; 2) the frequency of memory B cells was reduced; and 3) reappearing B cells showed an enhanced expression of activation markers CD25 and CD69, and expressed significantly higher levels of costimulatory CD40 and CD86. T cells showed 1) a persistent increase in naive and 2) a decrease in terminally differentiated subsets.
Keywords: multiple sclerosis; anti-CD20 therapy; B cells; T cells; repletion
 
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