Effects of Glucocorticoid Treatment on CD25⁻FOXP3⁺ Population and Cytokine-Producing Cells in Rheumatoid Arthritis

Rheumatology (Oxford). 2012 Jul;51(7):1198-207. doi: 10.1093/rheumatology/kes039. Epub 2012 Mar 24.

Abstract

Objectives: 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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / metabolism
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cytokines / biosynthesis
  • Cytokines / genetics*
  • DNA / genetics
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / drug effects
  • Forkhead Transcription Factors / genetics*
  • Gene Expression Regulation*
  • Genotype
  • Glucocorticoids / pharmacology*
  • Humans
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Interleukin-2 Receptor alpha Subunit / drug effects
  • Interleukin-2 Receptor alpha Subunit / genetics*
  • Intracellular Fluid / drug effects
  • Intracellular Fluid / metabolism
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Young Adult

Substances

  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Glucocorticoids
  • Interleukin-2 Receptor alpha Subunit
  • DNA