title: Effects of glucocorticoid treatment on CD25⁻FOXP3⁺ population and cytokine-producing cells in rheumatoid arthritis.
abstract: OBJECTIVE
  To investigate CD25(-)FOXP3(+) cells in RA patients and their possible relationship with disease features and response to glucocorticoids (GCs).
  
  
  METHODS
  Peripheral blood mononuclear cells were collected from 147 RA patients, 29 healthy controls and 75 SLE patients as disease controls. The proportion of CD4(+)FOXP3(+) cells with negative, low or high CD25 expression and the levels of IL-10-, TNF-α-, IL-17- and IFNγ-producing cells were assessed by flow cytometry. The presence of the high IL-10 genotype (-1082GG), associated with good response to GC, was determined by PCR amplification and hybridization with allele-specific fluorescently labelled probes. Data were related to treatment and clinical parameters.
  
  
  RESULTS
  The CD25(-)FOXP3(+) population was significantly increased in RA patients and negatively correlated with DAS-28 and other disease parameters. The IL-10 genotype did not influence the frequency of these cells in controls or the entire RA group; however, GC-treated patient carriers of the high IL-10 genotype presented significantly higher levels of this population in addition to an increased percentage of IL-10-secreting cells and relatively low amounts of TNF-α-, IFN-γ- and IL-17-positive cells. Finally, a prospective study confirmed that genetically high IL-10 producers significantly increase CD25(-)FOXP3(+) cells after 6 months of GC treatment.
  
  
  CONCLUSIONS
  The present study provides the first evidence of increased CD25(-)FOXP3(+) cells in RA patients, which were associated with disease activity and with GC treatment in carriers of the high IL-10 genotype, suggesting that this population plays a role in the clinical response to prednisone in RA.
authors.affiliation: Facultad de Medicina, Departamento de Biología Funcional, Area de Inmunología, University of Oviedo, Julián Clavería s/n, 33006 Oviedo, Spain.
authors.forename: Banesa
authors.initials: B
authors.lastname: de Paz
authors.forename: Catuxa
authors.initials: C
authors.lastname: Prado
authors.forename: Mercedes
authors.initials: M
authors.lastname: Alperi-López
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Ballina-García
authors.forename: Javier
authors.initials: J
authors.lastname: Rodriguez-Carrio
authors.forename: Patricia
authors.initials: P
authors.lastname: López
authors.forename: Ana
authors.initials: A
authors.lastname: Suárez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation; D005838:Genotype; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D005938:Glucocorticoids; D053645:Interleukin-2 Receptor alpha Subunit; D004247:DNA