There is now a general consensus that RA has a spectrum of disease stages that can begin many years before the onset of clinical symptoms. It is widely thought that understanding the complex... Show moreThere is now a general consensus that RA has a spectrum of disease stages that can begin many years before the onset of clinical symptoms. It is widely thought that understanding the complex interplay between genetics and environment, and their role in pathogenesis, is essential in gaining further insight into the mechanisms that drive disease development and progression. More than 100 genetic susceptibility loci have now been identified for RA through studies that have focused on patients with established RA compared with healthy controls. Studying the early preclinical phases of disease will provide valuable insights into the biological events that precede disease and could potentially identify biomarkers to predict disease onset and future therapeutic targets. In this review we will cover recent advances in the knowledge of genetic and environmental risk factors and speculate on how these factors may influence the transition from one stage of disease to another. Show less
Klein-Wieringa, I.R.; Linden, M.P.M. van der; Kwekkeboom, J.C.; Beelen, E. van; Helm-van Mil, A. van der; Kloppenburg, M.; ... ; Ioan-Facsinay, A. 2011
Introduction: Mast cells have been implicated to play a functional role in arthritis, especially in autoantibody-positive disease. Among the cytokines involved in rheumatoid arthritis (RA), IL-17... Show moreIntroduction: Mast cells have been implicated to play a functional role in arthritis, especially in autoantibody-positive disease. Among the cytokines involved in rheumatoid arthritis (RA), IL-17 is an important inflammatory mediator. Recent data suggest that the synovial mast cell is a main producer of IL-17, although T cells have also been implicated as prominent IL-17 producers as well. We aimed to identify IL-17 expression by mast cells and T cells in synovium of arthritis patients.Methods: Synovial samples of anticitrullinated protein antibody-positive (ACPA+) and ACPA-negative (ACPA-) RA and osteoarthritis (OA) patients were stained for IL-17 in combination with CD117 (mast cells), CD3 (T cells) and CD68 (macrophages). Concentrations of IL-17 in synovial fluid were determined by ELISA.Results: The number of IL-17+ cells in synovium was comparable in all groups. Although the vast majority of IL-17+ cells are mast cells, no difference in the percentage of IL-17+ mast cells was observed. Nonetheless, levels of IL-17 in synovial fluid were increased in ACPA+ RA patients compared to ACPA-RA and OA patients.Conclusions: The synovial mast cell is the main IL-17+ cell in all three arthritis groups analyzed. These data are relevant for studies aimed at blocking IL-17 in the treatment of arthritis. Show less
