Distribution of circulating cells in systemic juvenile idiopathic arthritis across disease activity states

Macaubas, Claudia; Nguyen, Khoa D.; Deshpande, Chetan; Phillips, Carolyn; Peck, Ariana; Lee, Tzielan; Park, Jane L.; Sandborg, Christy; Mellins, Elizabeth

doi:10.1016/j.clim.2009.09.010

Cited by 63 publications

(59 citation statements)

References 63 publications

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“…Our results could support previous work which has revealed that it is mainly cells of myeloid lineage that participate in the pathogenesis of sJIA [25]. Contradicting our results, Macaubas et al showed a decrease not only in circulating mDCs, but also in pDCs, in patients with active sJIA [26].…”

Section: Hla-dr Positive Cells In Blood and Synovial Fluidsupporting

confidence: 92%

Identification of dendritic cells in the blood and synovial fluid of children with Juvenile Idiopathic Arthritis

Tabarkiewicz

Postępski²,

Olesińska³

et al. 2011

Folia Histochem Cytobiol.

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Childhood chronic arthritis of unknown etiology is known collectively as juvenile idiopathic arthritis (JIA) and consists of heterogeneous subtypes with unique clinical patterns of disease. JIA is the commonest rheumatic disease in children and may still result in significant disability, with joint deformity, growth impairment, and persistence of active arthritis into adulthood. Basic research is rather focused on rheumatoid arthritis, and this lead to small number of publications considering JIA. In this study we examine, by flow cytometry, the expression of dendritic cells (DCs) in the peripheral blood and synovial fluid of children with active JIA in a group of 220 patients. We reveal a significant decrease in the percentage of immature DCs in the blood of patients compared to control children. Surprisingly, we found higher percentages of mature circulating dendritic cells. Both populations of DCs, immature and mature, were accumulated in patients' synovial fluid. We also confirmed the presence of CD206 + /CD209 + in JIA samples, which can represent a population of macrophages with dendritic cells morphology. Our results support the thesis that dendritic cells are crucial in the induction and maintenance of autoimmune response and local inflammation during juvenile idiopathic arthri-

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Section: Hla-dr Positive Cells In Blood and Synovial Fluidsupporting

confidence: 92%

Identification of dendritic cells in the blood and synovial fluid of children with Juvenile Idiopathic Arthritis

Tabarkiewicz

Postępski²,

Olesińska³

et al. 2011

Folia Histochem Cytobiol.

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“…Although we have not dissected the functional role of Vg9 + T cells in this subset in particular, our previous results (13) indicate that Vg9 + T cells in the SF of systemic JIA patients can respond to IPP. Taken together with the data of Macaubas et al (27), it could be postulated that during acute flares of systemic JIA, PB Vg9 + T cells migrate to synovium, where they may secrete TNF-a and IFN-g, thus contributing to local inflammation.…”

Section: Discussionmentioning

confidence: 61%

“…To test this postulation, multivariate correlations between the number and function of Treg relevant to autoreactive SF CD4 + T cells and the IPP-dependent responses of SF Vg9 + T cells and disease outcomes will be required to dissect the relative importance of each mechanism in the different subgroups of JIA patients. Interestingly in this regard, Macaubas et al (27) recently reported a downregulation of PB gd T cells, but not of NK cells, during acute exacerbations of systemic JIA specifically, suggesting a unique and specific role of gd T cells during flares of disease in this particular subset of JIA patients. Although we have not dissected the functional role of Vg9 + T cells in this subset in particular, our previous results (13) indicate that Vg9 + T cells in the SF of systemic JIA patients can respond to IPP.…”

Section: Discussionmentioning

confidence: 99%

Cellular Interactions of Synovial Fluid γδ T Cells in Juvenile Idiopathic Arthritis

Bendersky

Marcu-Malina

Berkun

et al. 2012

The Journal of Immunology

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The pathogenesis of juvenile idiopathic arthritis (JIA) is thought to involve multiple components of the cellular immune system, including subsets of γδ T cells. In this study, we conducted experiments to define the functional roles of one of the major synovial fluid (SF) T cell subsets, Vγ9+Vδ2+ (Vγ9+) T cells, in JIA. We found that as opposed to CD4+ T cells, equally high percentages (∼35%) of Vγ9+ T cells in SF and peripheral blood (PB) produced TNF-α and IFN-γ. Furthermore, stimulation with isopentenyl pyrophosphate (IPP), a metabolite in the mevalonate pathway, which is a specific potent Ag for Vγ9Jγ1.2+ T cells, similarly amplified cytokine secretion by SF and PB Vγ9+ T cells. Significantly, the SF subset expressed higher levels of CD69 in situ, suggesting their recent activation. Furthermore, 24-h coculturing with SF-derived fibroblasts enhanced CD69 on the SF > PB Vγ9+ T cells, a phenomenon strongly augmented by zoledronate, a farnesyl pyrophosphate synthase inhibitor that increases endogenous intracellular IPP. Importantly, although Vγ9+ T cell proliferation in response to IPP was significantly lower in SF than PBMC cultures, it could be enhanced by depleting SF CD4+CD25+FOXP3+ cells (regulatory T cells). Furthermore, coculture with the Vγ9+ T cells in medium containing zoledronate or IPP strongly increased SF-derived fibroblasts' apoptosis. The findings that IPP-responsive proinflammatory synovial Vγ9+ T cells for which proliferation is partly controlled by regulatory T cells can recognize and become activated by SF fibroblasts and then induce their apoptosis suggest their crucial role in the pathogenesis and control of synovial inflammation.

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“…Finally, several reports have shown a continued expression of activation markers while sJIA/AOSD was inactive, thus suggesting that quiescence in sJIA/AOSD may only represent a state of compensated inflammation [91]. This has been derived from observations of elevated levels of monocyte surface markers (CD14 and CD16), serum amyloid A, MIF, and IL-18.…”

Section: The Defective Immunoregulation Hypothesismentioning

confidence: 98%

Pathogenesis of adult-onset Still’s disease: new insights from the juvenile counterpart

et al. 2014

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Adult-onset Still's disease (AOSD) is a rare inflammatory disease characterized by the classical triad of daily fever, arthritis, and typical salmon-colored rash. Recent accumulation of knowledge, mostly arising from hereditary autoinflammatory diseases and from the systemic-onset juvenile idiopathic arthritis (sJIA), has given raise to new hypotheses on the pathophysiology of AOSD. In this review, we first discuss on the continuum between AOSD and sJIA. Then, we summarize current hypotheses on the underlying pathogenesis: (1) an infectious hypothesis; (2) an autoinflammatory hypothesis; (3) a lymphohistiocytic hypothesis; and (4) a hyperferritinemic hypothesis. Finally, we present the recent data suggesting that patients with AOSD fall into two distinct subgroups with different courses, one with prominent systemic features and one with chronic arthritis.

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Distribution of circulating cells in systemic juvenile idiopathic arthritis across disease activity states

Cited by 63 publications

References 63 publications

Identification of dendritic cells in the blood and synovial fluid of children with Juvenile Idiopathic Arthritis

Identification of dendritic cells in the blood and synovial fluid of children with Juvenile Idiopathic Arthritis

Cellular Interactions of Synovial Fluid γδ T Cells in Juvenile Idiopathic Arthritis

Pathogenesis of adult-onset Still’s disease: new insights from the juvenile counterpart

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