Assessment of CD40 and CD40L expression in rheumatoid arthritis patients, association with clinical features and DAS28

Clin Exp Med. 2019 Nov;19(4):427-437. doi: 10.1007/s10238-019-00568-5. Epub 2019 Jul 16.

Abstract

The predominance of the effector mechanisms by CD4 + T cells is a characteristic of inflammatory autoimmune diseases such as rheumatoid arthritis (RA). The CD40/CD40L costimulatory pathway contributes to these pathogenic mechanisms by promoting autoantibody production and inflammation. Aberrant expression of CD40 and CD40L in RA patients has been shown, the latter prevailing in females. However, contrasting results have emerged regarding the clinical associations of these findings. We determined the association of CD40 and CD40L expression with the clinical activity evaluated through DAS28 in RA patients. A total of 38 female RA patients and 10 age- and sex-matched control subjects were included. CD40 and CD40L mRNA expression was quantified by real-time qPCR, cell surface proteins were determined by flow cytometry, and protein soluble forms were determined by ELISA. The expansion of a CD4 + T cell subpopulation expressing CD40 was identified in the RA group. In addition, high frequencies of CD4 + CD40L + T cells expressing high levels of CD40L, increased levels of sCD40L and overexpression of CD40L mRNA were observed in these patients. Moreover, there was a gradual increase in CD40L when data were stratified according to DAS28, except for very active patients. No correlation was observed between the levels of mRNA, cell surface protein and soluble protein of CD40 and CD40L with the clinical features of RA patients. There is an altered expression of CD40L in female RA patients in association with clinical activity assessed by DAS28, these findings support the evidence that suggests CD40L as a marker of clinical activity.

Keywords: CD40; CD40L; DAS28; Rheumatoid arthritis.

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Biomarkers / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD40 Antigens / genetics*
  • CD40 Antigens / metabolism*
  • CD40 Ligand / genetics*
  • CD40 Ligand / metabolism*
  • Case-Control Studies
  • Female
  • Humans
  • Middle Aged
  • Severity of Illness Index
  • Up-Regulation

Substances

  • Biomarkers
  • CD40 Antigens
  • CD40 Ligand