SERUM P55 AND P75 TUMOR-NECROSIS-FACTOR RECEPTORS AS MARKERS OF DISEASE-ACTIVITY IN JUVENILE CHRONIC ARTHRITIS

Objective-To determine the expression of tumour necrosis factor alpha (TNF alpha) and its soluble receptors (p55 and p75) in the sera and sy novial fluid of patients with juvenile chronic arthritis (JCA), and th eir correlation with disease activity parameters. Methods-Ninety eight sera from 45 patients with JCA (14 systemic, 12 polyarticular, 19 pau ciarticular), 20 sera from age matched healthy controls, and five syno vial fluids from five antinuclear antibody (ANA) positive pauciarticul ar JCA patients were tested for the presence of TNF alpha, soluble TNF receptors p55 and p75 (sTNFRp55, sTNFRp75), and interleukin-6 (IL-6) by an enzyme amplified sensitivity immunoassay. Physician global estim ate of disease activity, weekly fever score and joint score, C reactiv e protein (CRP), erythrocyte sedimentation rate (ESR), and haemoglobin concentration were evaluated as parameters of disease activity. The e xpression of p55 and p75 on peripheral mononuclear cells (MNCs) from f ive patients with systemic JCA and synovial MNCs from five ANA positiv e patients with pauciarticular JCA was evaluated by now cytometry. Res ults-TNF alpha serum concentrations did not differ significantly betwe en the patients with active JCA and the control group. No correlation was found between TNF alpha and parameters of disease activity, but bo th p55 and p75 showed a significant positive correlation with the phys ician global estimate of disease activity (p < 0.001), ESR (p < 0.001) , CRP (p < 0.001), and serum concentrations of IL-6 (p < 0.001). Serum concentrations of haemoglobin correlated inversely with the concentra tions of p55 and p75 (p < 0.001). Synovial lymphocytes selectively exp ressed the p75 surface receptor. Conclusions-sTNFRp55 and sTNFRp75 eac h represent a sensitive marker of disease activity in JCA. Their incre ased expression in biological fluids may support the hypothesis that T NF alpha has a role in the pathogenesis of JCA.