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

Bjoernhart, B.; Svenningsen, P.; Gudbrandsdottir, S.; Zak, M.; Nielsen, S.; Bentzen, K.; Müller, K.

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.