title: CTLA-4-Ig therapy diminishes the frequency but enhances the function of Treg cells in patients with rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease. Natural T regulatory (nTreg) cells, which constitutively express the CTLA-4 molecule, have an important role in the pathogenesis of autoimmune conditions. Although it has been reported that biological agents are able to modulate the levels or function of Treg lymphocytes, the possible effect of Abatacept (CTLA-4-Ig) therapy on these cells has not been studied in autoimmune conditions. We explored the effect of Abatacept therapy on Treg cells in patients with RA. The number of different subsets of Treg cells was analyzed by flow cytometry in the peripheral blood from 45 patients with RA that were (n = 30) or not (n = 15) under Abatacept therapy as well as in 20 healthy controls. The function of Treg cells was assessed by an assay of inhibition of lymphocyte proliferation. We found that Abatacept therapy was associated with a significant diminution in the levels of CD4+CD25(bright)Foxp3+, and CD4+CTLA-4+ nTreg cells. In contrast, the regulatory function of CD4+CD25+ lymphocytes was significantly enhanced after the administration of Abatacept. Our data suggest that CTLA-4-Ig exerts a complex and interesting effect on Treg cells in patients with RA.
authors.affiliation: Department of Immunology, Facultad de Medicina, UASLP, Ave. V. Carranza 2405, 78210, San Luis Potosí, SLP, Mexico.
authors.forename: Crisol
authors.initials: C
authors.lastname: Álvarez-Quiroga
authors.forename: Carlos
authors.initials: C
authors.lastname: Abud-Mendoza
authors.forename: Lesly
authors.initials: L
authors.lastname: Doníz-Padilla
authors.forename: Amida
authors.initials: A
authors.lastname: Juárez-Reyes
authors.forename: Adriana
authors.initials: A
authors.lastname: Monsiváis-Urenda
authors.forename: Lourdes
authors.initials: L
authors.lastname: Baranda
authors.forename: Roberto
authors.initials: R
authors.lastname: González-Amaro
mesh_terms: D000069594:Abatacept; D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015704:CD4 Antigens / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018796:Immunoconjugates; D053645:Interleukin-2 Receptor alpha Subunit; D000069594:Abatacept