Early Joint Replacement in Juvenile Idiopathic Arthritis: Trend Over Time and Factors Influencing Implant Survival.

OBJECTIVE: To describe early prosthesis implantations in a cohort of patients with juvenile idiopathic arthritis (JIA) followed in a tertiary referral hospital and to analyze possible factors influencing implant survival. METHODS: This was a retrospective cohort study. Charts of all patients with JIA who underwent total joint replacement at Gaetano Pini Hospital, Milan, Italy from January 1992 to June 2019 were retrieved, and relevant data were analyzed. RESULTS: Eighty-five patients met the inclusion criteria for this study, with a median follow-up period of 17.2 years. The median age at first prosthesis was 22.7 years. The total number of replaced joints was 198 over a period of 27 years. The hip was the most frequently replaced joint, accounting for almost two-thirds of the total number of implants; the other one-third refers mostly to knee implants. Polyarticular JIA and systemic JIA were the most represented JIA categories in the study cohort. A significant upward trend of the age at arthroplasty and of disease duration before arthroplasty over decades was found. The rates of implant survival at 5, 10, and 15 years were comparable (from 84% to 89%); 50% of implants lasted ≥20 years. CONCLUSION: We reported retrospective data on early joint replacement in a cohort of patients with JIA. We observed a progressive and significant upward trend of both age at arthroplasty and disease duration before the first arthroplasty over time. The JIA category, year of implant, and presence of complications significantly affected implant survivorship.

Anti-inflammatory Effect of Somatostatin Analogue Octreotide on Rheumatoid Arthritis Synoviocytes.

Somatostatin and its analogues are known to have modulatory effects on immune response and their anti-proliferative, anti-angiogenic, and analgesic properties make them attractive candidates for a therapeutic use in immune-mediated diseases, such as rheumatoid arthritis. Here, we demonstrate the ability of the somatostatin analogue octreotide to inhibit interleukin-15 and to increase interleukin-10 production by rheumatoid arthritis fibroblast-like synovial cells maintained in a chronic inflammatory state. We also prove that the inhibitory effect of octreotide on interleukin-15 and tumor necrosis factor-α production depended on the increase in interleukin-10, since neutralizing anti-interleukin-10 antibody was able to partially reverse this inhibition. In addition, our observations suggest an octreotide control on purinergic signaling, with an inhibitory effect on purinergic P2X and P2Y receptors activation. This would have great implications, considering the roles of P2 receptors in the onset of inflammation. Data here reported extend knowledge on the biological action of octreotide and underline its multiple effects on immune response, which could make octreotide an attractive and valid support for the therapy of diseases where several inflammatory mediators are involved, such as rheumatoid arthritis, and in which the simultaneous action on different aspects can be a successful strategy.

Differences in serum and synovial CD4+ T cells and cytokine profiles to stratify patients with inflammatory osteoarthritis and rheumatoid arthritis.

BACKGROUND: The aim was to investigate CD4+T-cell subsets, immune cells and their cytokine profiles in blood and synovial compartments in rheumatoid arthritis (RA) and inflammatory osteoarthritis (OA) to define specific immune signatures. METHODS: Peripheral blood, synovial fluid (SF) and synovial membranes (SM) of RA and OA patients were analyzed. CD4+T-cell subset frequencies were determined by flow cytometry, and cytokine concentrations in serum and SF were measured by ELISA. RESULTS: In peripheral blood, OA patients had altered frequencies of regulatory T-cell subsets, and higher frequencies of Th17 and of Th1/17 cells than RA patients. In the synovial compartment of OA patients, conventional Th17 cells were largely excluded, while Th1/17 cells were enriched and more frequent than in RA patients. Conversely, in the synovial compartment of RA patients, regulatory T cells and Tfh cells were enriched and more frequent then in OA patients. IL-17 and Blys were increased both in serum and SF of RA patients, and correlated with autoantibodies and disease activity. Notably, Blys levels were already significantly elevated in RA patients with low disease activity score in 28 joints (DAS28) and without autoantibody positivity. CONCLUSIONS: Although patients with inflammatory OA have immune activation in the synovial compartment, they display different T-cell subset frequencies and cytokine profiles. Soluble mediators such as Blys might help to discriminate mild clinical forms of RA from inflammatory OA particularly at the onset of the disease.

Optimized "in vitro" culture conditions for human rheumatoid arthritis synovial fibroblasts.

The composition of synovial fluid in rheumatoid arthritis (RA) is complex and strongly influences the microenvironment of joints and it is an inseparable element of the disease. Currently, "in vitro" studies are performed on RA cells cultured in the presence of either recombinant proinflammatory cytokines-conditioned medium or medium alone. In this study, we evaluated the use of synovial fluid, derived from RA patients, as optimal culture condition to perform "in vitro" studies on RA synovial fibroblasts. We observed that synovial fluid is more effective in inducing cell proliferation with respect to TNF-alpha or culture medium alone. Spontaneous apoptosis in fibroblasts was also decreased in response to synovial fluid. The expression of proinflammatory cytokines in the presence of synovial fluid was significantly elevated with respect to cells cultured with TNF-alpha or medium, and the overall morphology of cells was also modified. In addition, modulation of intracellular calcium dynamics elicited in response to synovial fluid or TNF-alpha exposure is different and suggests a role for the purinergic signalling in the modulation of the effects. These results emphasize the importance of using RA synovial fluid in "in vitro" studies involving RA cells, in order to reproduce faithfully the physiopathological environmental characteristic of RA joints.