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Войти в исследования Multiple sclerosis and related disorders · 2024
Rapid depletion of CD20+ B and T cells following ofatumumab therapy onset.
СтатьяНазвание и аннотация: Перевод в очереди
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Konen Franz Felix, Gingele Stefan, Hümmert Martin W, Möhn Nora, Streichert Anna Lena, Kretschmer Julian Reza, Grote-Levi Lea, Nay Sandra, Seeliger Tabea, Ratuszny Dominica, Jendretzky Konstantin Fritz, Tkachenko Daria, Jacobs Roland, Skripuletz Thomas, Schwenkenbecher Philipp
Аннотация
BACKGROUND: The humanized monoclonal anti-CD20-antibody ofatumumab is highly effective in treating relapsing multiple sclerosis (MS).
OBJECTIVE: This study aimed to investigate the immanent effect of ofatumumab on the peripheral immune system, particularly targeting B and T cells expressing CD20.
METHODS: Blood samples of 53 MS patients receiving ofatumumab were collected prior to first application and after one week, two weeks and three months. Multicolor flow cytometry was used to phenotype peripheral blood mononuclear cells, and immunoglobulin (Ig) concentrations were measured by nephelometry.
RESULTS: Among CD20+ lymphocytes, 13 % co-expressed CD3 (identifying them as CD3+CD20+ T lymphocytes), with a noticeable shift in the CD4/CD8-ratio towards CD8+ T cells. One week after administering ofatumumab, a significant reduction of CD20+ lymphocytes with complete depletion of CD3+CD20+ T lymphocytes was observed, persisting during the investigation period. During the treatment, IgM levels showed a slight but significant decrease, whereas IgA and IgG levels remained stable.
CONCLUSION: Ofatumumab effectively depletes CD20+ lymphocytes already after the first administration. This depletion affects not only B cells, but also a small proportion of T cells (CD3+CD20+), affirming the hypothesis that the anti-inflammatory effects of CD20+ cell depletion might extend to the reduction of CD3+CD20+ T lymphocytes.
OBJECTIVE: This study aimed to investigate the immanent effect of ofatumumab on the peripheral immune system, particularly targeting B and T cells expressing CD20.
METHODS: Blood samples of 53 MS patients receiving ofatumumab were collected prior to first application and after one week, two weeks and three months. Multicolor flow cytometry was used to phenotype peripheral blood mononuclear cells, and immunoglobulin (Ig) concentrations were measured by nephelometry.
RESULTS: Among CD20+ lymphocytes, 13 % co-expressed CD3 (identifying them as CD3+CD20+ T lymphocytes), with a noticeable shift in the CD4/CD8-ratio towards CD8+ T cells. One week after administering ofatumumab, a significant reduction of CD20+ lymphocytes with complete depletion of CD3+CD20+ T lymphocytes was observed, persisting during the investigation period. During the treatment, IgM levels showed a slight but significant decrease, whereas IgA and IgG levels remained stable.
CONCLUSION: Ofatumumab effectively depletes CD20+ lymphocytes already after the first administration. This depletion affects not only B cells, but also a small proportion of T cells (CD3+CD20+), affirming the hypothesis that the anti-inflammatory effects of CD20+ cell depletion might extend to the reduction of CD3+CD20+ T lymphocytes.