The tumour necrosis factor family of receptors/ligands in the serum of patients with rheumatoid arthritis

Abstract

We investigated the serum concentration of the tumour necrosis factor (TNF) family ligands (TNF-alpha and TNF-beta) and their soluble receptors (sTNF-R p55 and sTNF-R p75) in 66 patients with rheumatoid arthritis (RA) and 14 healthy subjects as a control group, using an enzyme-linked immunosorbent assay (ELISA). We examined a possible association between the serum levels of these proteins and RA activity according to the Mallya & Mace scoring system and Ritchie's index. We also evaluated the correlation between the serum levels of ligands and their soluble receptors as well as the ligands and receptors concentration and the duration of the disease. TNF-alpha, sTNF-R p55 and sTNF-R p75 were detectable in the serum of all 66 patients and 14 healthy individuals. In contrast, TNF-beta was measurable in only 14(21.9%) patients with RA and in none of the control subjects. The highest TNF-alpha, sTNF-R p55 and sTNF-R p75 levels were found in those patients in stage 4 of the disease, and the lowest in the control group. We found a positive correlation between sTNF-R p55 and sTNF-R p75 concentrations and Ritchie's index and no correlation with TNF-alpha and TNF-beta. TNF-alpha, sTNF-R p55 and sTNF-R p75 serum levels correlated positively with the duration of the disease, but levels of TNF-beta did not. We observed a positive correlation between the concentrations of TNF-alpha with sTNF-R p55 and with sTNF-R p75, as well as between both soluble receptors. In contrast, we have not observed any correlation between the serum level of TNF-beta with TNF-alpha, sTNF-R p55, and sTNF-R p75. Our studies indicate that TNF-alpha, sTNF-R p55 and sTNF-R p75, but not TNF-beta (lymphotoxin alpha) are good markers of RA activity and that these proteins play an important role in the pathogenesis of this disease.