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Impact of cladribine therapy on changes in circulating dendritic cell subsets, T cells and B cells in patients with
Krystyna Mitosek-Szewczyk1, Jacek Tabarkiewicz, Barbara Wilczynska
1Department of Child Neurology, Medical University in Lublin, ul. Chodźki 2, Lublin, Poland. krystyna.mitosek@am.lublin.pl
Insights
Cladribine therapy for multiple sclerosis significantly increases plasmacytoid dendritic cells and decreases B and T cells. This immune modulation may offer a dual benefit in treating MS by inducing IFN-alfa and reducing autoimmune responses.
Area of Science:
- Immunology
- Neuroscience
- Pharmacology
Background:
- Cladribine selectively reduces peripheral T and B cell populations in multiple sclerosis (MS) patients.
- Dendritic cell (DC) populations, including myeloid DCs (CD1c+/CD19-) and plasmacytoid DCs (CD303+/CD123+), were investigated post-cladribine therapy.
- Analysis included CD19+ B lymphocytes, CD3+ T lymphocytes, and CD4+/CD8+ T cell subpopulations.
Purpose of the Study:
- To determine the effects of cladribine therapy on specific immune cell populations in patients with secondary progressive multiple sclerosis (SP MS).
- To analyze changes in myeloid and plasmacytoid dendritic cell subsets, B cells, and T cell subpopulations following cladribine treatment.
Main Methods:
- Fifty SP MS patients were enrolled and assessed according to McDonald's criteria (2001).
- Blood samples were collected pre-treatment and after each of the five cladribine courses.
- Flow cytometry was utilized to analyze DC subsets, T cells, and B cells.
Main Results:
- Myeloid DCs (CD1c+/CD19-) showed no significant change (p=0.73175).
- Plasmacytoid DCs (CD303+/CD123+) significantly increased (p=0.00034), altering the myeloid to plasmacytoid DC ratio (p=0.00273).
- B lymphocytes (CD19+) significantly decreased (p=0.00005), with significant changes observed in CD4+ (p=0.00191) and CD3+ (p=0.01822) cells, while CD8+ cells showed a trend (p=0.05760).
Conclusions:
- A significant increase in circulating CD303+ dendritic cells, which produce IFN-alfa, was observed.
- A rapid and significant decrease in B cells and CD4+ Th cells suggests a reduction in immune response induction.
- Cladribine's beneficial effects in MS may stem from promoting IFN-alfa-producing DCs and modulating lymphocytes involved in autoimmune responses against myelin.
Background:
Cladribine causes sustained reduction in peripheral T and B cell populations while sparing other immune cells. We determined two populations of dendritic cells (DCs): namely CD1c(+)/CD19(-) (myeloid DCs) and CD303(+)/CD123(+) (plasmacytoid DCs), CD19(+) B lymphocytes, CD3(+) T lymphocytes and CD4(+) or CD8(+) subpopulations in patients with multiple sclerosis after cladribine therapy.
Methods:
We examined 50 patients with secondary progressive multiple sclerosis (SP MS) according to McDonalds et al.'s criteria, 2001 [15]. Blood samples were collected before the initiation of cladribine therapy and after 1st, 2nd, 3th, 4th and 5th courses of treatment. DC subsets, T and B cells were analyzed by flow cytometry.
Results:
During cladribine treatment the myeloid DCs CD1c(+)/CD19(-) did not change (p=0.73175), and the plasmacytoid DCs CD303(+)/CD123(+) significantly increased (p=0.00034) which resulted in significant changes in the ratio of myeloid DCs to plasmacytoid DCs (p=0.00273). During therapy, B lymphocyte CD19(+) significantly decreased (p=0.00005) and significant changes in CD4(+) cells (p=0.00191), changes in CD8(+) cells (p=0.05760) and significant changes in CD3(+) (p=0.01822) were found.
Conclusions:
We noticed significant trend to increase the CD303(+) circulating the dendritic cells. This population produces large amounts of IFN-alfa. We found significant and rapid decrease in B cells and CD4(+) Th cells. Our results suggest two possible ways of beneficial cladribine influence on immune system in MS. Induction of IFN-alfa producing cells and their predominance over BDCA-1(+) DCs, which are associated with cytotoxic response. Additionally, cladribine could influence two populations of lymphocytes: B cells and Th lymphocytes responsible for induction of immune response against myelin antigens.
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