title: Impact of cladribine therapy on changes in circulating dendritic cell subsets, T cells and B cells in patients with multiple sclerosis.
abstract: 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.
authors.affiliation: Department of Child Neurology, Medical University in Lublin, ul. Chodźki 2, Lublin, Poland. krystyna.mitosek@am.lublin.pl
authors.forename: Krystyna
authors.initials: K
authors.lastname: Mitosek-Szewczyk
authors.forename: Jacek
authors.initials: J
authors.lastname: Tabarkiewicz
authors.forename: Barbara
authors.initials: B
authors.lastname: Wilczynska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Lobejko
authors.forename: Jerzy
authors.initials: J
authors.lastname: Berbecki
authors.forename: Marcin
authors.initials: M
authors.lastname: Nastaj
authors.forename: Ewa
authors.initials: E
authors.lastname: Dworzanska
authors.forename: Beata
authors.initials: B
authors.lastname: Kolodziejczyk
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Stelmasiak
authors.forename: Jacek
authors.initials: J
authors.lastname: Rolinski
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects*; D017338:Cladribine / Q000494:pharmacology* / Q000627:therapeutic use; D003713:Dendritic Cells / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: D015703:Antigens, CD; D007166:Immunosuppressive Agents; D017338:Cladribine
keywords: B cell; Cladribine; Dendritic cells; Immunosuppresant; Multiple sclerosis; T cell