Plasma TNF-Binding Capacity and Soluble TNF Receptors in Patients with Juvenile Idiopathic Arthritis

Background:  Unbalanced production of proinflammatory cytokines may be related to disease progression in rheumatoid arthritis and juvenile idiopathic arthritis (JIA). Within the TNF system, the two agonists, TNF-α and TNF-β, also called lymphotoxin-α (LT), are bound by soluble TNF receptors (sTNFR-I and -II) that act as natural inhibitors of TNF-induced inflammation. We investigated the plasma levels of sTNFR-I in parallel with LT-binding capacity (LTBC) in patients with JIA.
Methods:  The levels of sTNFR-I were measured by ELISA (R&D). LTBC was determined by spiking diluted plasma samples with recombinant LT. Detectable LT was measured by an in-house ELISA measuring unbound LT only. LTBC was expressed in arbitrary units (AUs) as the percentage value of bound LT to added LT.
Result:  In contrast to previous findings of elevated sTNFR levels in patients with various chronic inflammatory diseases, we found slightly reduced sTNFR-I levels in JIA patients ( n  = 123) compared with age-matched healthy controls ( n  = 37): 1077 pg/ml (819–2280) versus 1185 pg/ml (625–2303) [median (range)], P  = 0015. However, the sTNFR-I levels correlated positively with the number of active joints, physicians' global assessment and CRP. In contrast, patient LTBC values were elevated compared to healthy controls: 44 AU (36–52) versus 31 AU (13–41), P  < 0.0001.
Conclusion:  Despite overall slightly reduced plasma levels of sTNFR-I, the capacity to bind TNF was increased in plasma samples from JIA patients. Studies to identify the TNF-binding substances in plasma are in progress.