Adalimumab Effectively Decreases Inflammation Downstream of TNFα Signaling in Synoviocytes from Extended Oligoarticular Juvenile Idiopathic Arthritis

IntroductionFibroblast-like synoviocytes (FLS) play a critical role in inflammation that contributes to disease progression in juvenile idiopathic arthritis (JIA). In rheumatoid arthritis (RA), FLS express tumor necrosis factor alpha (TNF alpha). TNF alpha signaling has been shown to be upstream of transforming growth factor beta (TGF beta) signaling. Overexpression of TNF alpha and TGF beta, as well as related proteins, can cause increased inflammation in RA. In this study, we examine the effects of inhibiting TNF alpha signaling with adalimumab on FLS isolated from synovial fluid of patients with JIA.MethodsSynovial fluid samples were selected from 41 patients in our repository. Of these samples, 23 were diagnosed with persistent oligoarticular JIA and 18 were diagnosed with extended oligoarticular JIA. All samples were taken prior to patients extending to a polyarticular course, or what we termed extended-to-be (ETB), and were on no medications or nonsteroidal anti-inflammatory drugs (NSAIDs) only at the time of arthrocentesis. For cell studies, FLS were isolated from synovial fluid and treated with adalimumab for 24 h. Protein antibody arrays were performed by RayBiotech, Inc. according to their protocols.ResultsIn persistent FLS, TNF alpha (fold change [FC] = 1.2 p = 0.001), TGF beta (FC = 1.5 p = 0.001), lymphotoxin alpha (LT alpha) (FC = 4.3 p = 0.015), soluble tumor necrosis factor receptor 1 (sTNFRI) (FC = 5.1 p = 0.008), and soluble tumor necrosis factor receptor 2 (sTNFRII) (FC = 3.8 p = 0.025) were significantly elevated in adalimumab treated cells compared to untreated cells. In ETB FLS, TNF alpha was significantly elevated (FC = 1.04 p = 0.023) while TGF beta (FC = 1.03 p = 0.037) was significantly decreased in adalimumab-treated cells compared to untreated cells.ConclusionsThis data suggests that, after only 24 h, adalimumab is effective at decreasing inflammation that occurs downstream of initial TNF alpha signaling in extended-to-be fibroblast-like synoviocytes.

Automated summary

This study examines the effects of inhibiting TNF alpha signaling with adalimumab on fibroblast-like synoviocytes (FLS) isolated from synovial fluid of patients with juvenile idiopathic arthritis (JIA). The results suggest that adalimumab can reduce inflammation in FLS associated with TNF alpha.