Background Identification of autoantibodies associated with rheumatoid arthritis has been of major interest. In this context, we have previously identified for the first time α-enolase (ENO) as a new auto-antigen in early RA. ENO is an evolutionary conserved protein involved both in glycolysis pathway and as a plasminogen receptor which confer it a role in anti-infectious inflammatory response. In vivo, preliminary studies showed that ENO had immunomodulatory effect in the collagen induced arthritis mouse model1. Objectives To better understand the immunological mechanisms of ENO, the aim of this in vitro study was to determine the effects of ENO on PBMCs from healthy donors. Methods : In one hand, PBMCs or different cell types (monocytes, B and T cells, and immature dendritic cells [iDC]) (n=3) were cultured with ENO (20 µg/mL) or Bovine Serum Albumin (20 µg/mL). TNFα and IL-10 production was measured in the supernatants by ELISA at different times. On the other hand, TNFα and IL-10 production were evaluated in PBMCs, monocytes or B and T cells after LPS stimulation and pre-incubation with ENO for 24h (n=3). Cytometric analyses have evaluated the ability of ENO to inhibit the differentiation of monocytes into iDC or iDC into mature DC. Before differentiation into iDC (GM-CSF and IL-4), monocytes (1.106cells/mL) were incubated with ENO (20 or 50µg/mL) for 24h. Results In cultures of PBMCs, monocytes or iDC, ENO induces, dose dependently, an early production of TNFα followed by extended secretion of IL-10. PBMCs or individual cells (monocytes, B and T cells) stimulated by LPS secreted successively TNFα and IL-10, while PBMCs or individual cells, stimulated by LPS but previously incubated with ENO for 24h did not secrete these cytokines. In contrast to LPS, ENO did not induce differentiation of immature dendritic cells into mature cells. Moreover, ENO has the capacity to inhibit differentiation from monocytes to iDC. Conclusions This study suggests that ENO has no pro-inflammatory effect unlike LPS. Indeed, ENO might have immunomodulatory properties via IL-10 production. Others studies focused on an extended cytokine panel and different signaling pathways are underway to better understand the immunological mechanisms induced by ENO. References C. GUILLOU et al., Arthritis and Rheumatism 2011, 63:S815. Disclosure of Interest None Declared
BACKGROUND AND AIMS Little is known about the long-term outcome during adulthood of childhood onset idiopathic nephrotic syndrome (INS). We aimed to determine which patients require long-term follow up after transition, to identify risk factors of relapse and to analyze treatment strategies. METHOD In this monocentric retrospective study, we included all patients admitted in our adult nephrology department with INS diagnosed during childhood. Patients who reached kidney failure during childhood were excluded. Data regarding the outcome at adult age were obtained through clinical database and medical charts. RESULTS Eighty-two patients (male/female = 2/1) were included, with a median age at diagnosis of 3.9 years (1.2–16.5). Sixty-eight patients had steroid-sensitive INS, including 52 with steroid-dependent nephrotic syndrome or frequently relapsing nephrotic syndrome. Fourteen patients had steroid-resistant nephrotic syndrome. A total of 89% of patients received corticosteroid sparing treatment during childhood. Median follow-up during adulthood was 6.2 (0.3–25) years. A total of 71% of patients experienced at least one relapse during adulthood. The total number of relapses during childhood and the number of relapses per year during childhood, reflecting disease activity, were significantly higher in patients who experienced relapses during adulthood than in patients who did not (Figure 1). The risk of relapse during adulthood was also significantly associated with the need for immunosuppressive regimen at the time of the transition visit (P = 0.002). To promote the successful transition of young people, we propose to organize a transition visit where the adolescent/young adult is seen jointly by pediatric and adult nephrologists, as it was done for 68% of patients in this study. The relapse rate was significantly lower (50%) in the subgroup of patients who had such a transition visit. We also found that relapse during the first two-years of adulthood follow-up was significantly associated with the risk of further relapse, highlighting the need for a close follow-up during the transition period. A total of 45% of patients received corticosteroid sparing treatment during adulthood, mainly mycophenolate mofetil (N = 23), calcineurin inhibitors (N = 21) and rituximab (N = 12). The main complications were high blood pressure (20/82, 26%) and osteopenia (19/26, 73% when bone densitometry was performed). Only one thrombo-embolic event and three severe infections were reported. At last follow-up, median eGFR was 87.1 (23.4–150.8) mL/min/1.73 m². CONCLUSION The incidence of relapses in adulthood is high in patients with active disease during childhood. A long-term follow-up is mandatory in these patients. Whereas renal function remained normal in most patients, high blood pressure and osteopenia were frequent and should be carefully monitored during adulthood. Transition visit should be carefully coordinated to prevent the risk of nonadherence.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.