TNFα polymorphism as marker of immunosenescence for rheumatoid arthritis patients

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Expansion of CD4+CD28null, 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+CD28null cells has been related to TNFα exposure, nothing is known about the possible role of genetic variants of this cytokine.


Participants were genotyped for TNFA rs1800629 (−308 G > A) and frequency of the CD4+CD28null, regulatory T cells and Th1 cells subsets were quantified in peripheral blood samples by flow cytometry in 129 RA patients and 33 healthy controls.


The expansion of CD4+CD28null 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+CD28null 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.


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.

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