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Repeated iv anti-CD20 treatment in multiple sclerosis: Long-term effects on peripheral immune cell subsets.
Feige, Julia; Moser, Tobias; Akgün, Katja; Schwenker, Kerstin; Hitzl, Wolfgang; Haschke-Becher, Elisabeth; Ziemssen, Tjalf; Sellner, Johann.
Afiliación
  • Feige J; Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria.
  • Moser T; Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria.
  • Akgün K; Department of Neurology, Multiple Sclerosis Center, Center of Clinical Neuroscience, Carl Gustav Carus University Hospital, Technical University Dresden, Dresden, Germany.
  • Schwenker K; Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria.
  • Hitzl W; Research Management (RM): Biostatistics and Publication of Clinical Studies Team, Paracelsus Medical University, Salzburg, Austria.
  • Haschke-Becher E; Department of Ophthalmology and Optometry, Paracelsus Medical University, Salzburg, Austria.
  • Ziemssen T; Research Program Experimental Ophthalmology and Glaucoma Research, Paracelsus Medical University, Salzburg, Austria.
  • Sellner J; Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria.
Ann Clin Transl Neurol ; 11(2): 450-465, 2024 02.
Article en En | MEDLINE | ID: mdl-38204286
ABSTRACT

OBJECTIVE:

Repeated intravenous administration of anti-CD20 depleting monoclonal antibodies 6 months apart is among the highly effective treatment options in multiple sclerosis (MS). Here, we aimed to investigate peripheral immune cell subset depletion kinetics following either rituximab (RTX) or ocrelizumab (OCR) infusions in people with MS (pwMS).

METHODS:

We studied pwMS treated de-novo with either RTX (n = 7) or OCR (n = 8). The examinations were scheduled before the initiation of anti-CD20 therapy and every 12 weeks for up to 15 months. Immunophenotyping of immune cell subsets in peripheral blood was performed by multiparametric fluorescence cytometry.

RESULTS:

A significant, persistent decrease of CD19+ B cells was observed already with the first anti-CD20 infusion (p < 0.0001). A significant proportional reduction of memory B cells within the B-cell pool was achieved only after two treatment cycles (p = 0.005). We observed a proportional increase of immature (p = 0.04) and naive B cells (p = 0.004), again only after the second treatment cycle. As for the peripheral T-cell pool, we observed a continuous proportional increase of memory T helper (TH) cells/central memory TH cells (p = 0.02/p = 0.008), while the number of regulatory T cells (Treg) decreased (p = 0.007). The percentage of B-cell dependent TH17.1 central memory cells dropped after the second treatment cycle (p = 0.02). No significant differences in the depletion kinetics between RTX and OCR were found.

INTERPRETATION:

Peripheral immune cell profiling revealed more differentiated insights into the prompt and delayed immunological effects of repeated intravenous anti-CD20 treatment. The observation of proportional changes of some pathogenetically relevant immune cell subsets only after two infusion cycles deserves further attention.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esclerosis Múltiple Límite: Humans Idioma: En Revista: Ann Clin Transl Neurol Año: 2024 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esclerosis Múltiple Límite: Humans Idioma: En Revista: Ann Clin Transl Neurol Año: 2024 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Estados Unidos