TNFα polymorphism as marker of immunosenescence for rheumatoid arthritis patients

Exp Gerontol. 2015 Jan;61:123-9. doi: 10.1016/j.exger.2014.12.009. Epub 2014 Dec 13.


Background: Expansion of CD4(+)CD28(null), a common feature of immunosenescence, which has been reported in rheumatoid arthritis (RA) patients, may also be associated with a CD4(+) imbalance. Although the increase of CD4(+)CD28(null) cells has been related to TNFα exposure, nothing is known about the possible role of genetic variants of this cytokine.

Methods: Participants were genotyped for TNFA rs1800629 (-308 G>A) and frequency of the CD4(+)CD28(null), regulatory T cells and Th1 cells subsets were quantified in peripheral blood samples by flow cytometry in 129 RA patients and 33 healthy controls.

Results: The expansion of CD4(+)CD28(null) cells in RA patients was associated with TNFA genotype, even at diagnosis, and linked to markers of aggressive disease in patient carriers of the minor allele. Analysis of regulatory T cells and IFNγ-CD4(+) expression suggested that defective suppression and/or Th1-shift could underlie the expansion of this population in these patients. Finally, although treatment with TNFα-blockers reduced CD4(+)CD28(null) cells in most patients, only those carriers of the common GG genotype reached values within the range of HC and showed a disease activity improvement correlated to this decrease.

Conclusions: Our results provide evidence for a genetic basis of the premature immunosenescence of RA patients and highlight its potential role in clinical outcome after TNFα blockade.

Keywords: CD4(+)CD28(null) cells; Immunosenescence; Rheumatoid arthritis; TNFA polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / immunology*
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • CD28 Antigens / analysis
  • Female
  • Genetic Markers
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / genetics*


  • CD28 Antigens
  • Genetic Markers
  • Tumor Necrosis Factor-alpha