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1.
Artículo en Inglés | MEDLINE | ID: mdl-37669122

RESUMEN

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare condition characterized by fevers, rash, and arthralgia/arthritis. Most doctors treating AOSD in the Netherlands treat <5 patients per year. Currently, there is no internationally accepted treatment guideline for AOSD. OBJECTIVES: To conduct a Delphi panel aimed at reaching consensus about diagnostic and treatment strategies for patients with AOSD and to use the outcomes as a basis for a treatment algorithm. METHODS: The Delphi panel brought together 18 AOSD experts: rheumatologists, internists and paediatricians. The Delphi process consisted of 3 rounds. In the first two rounds, online list of questions and statements were completed. In the third round, final statements were discussed during a virtual meeting and a final vote took place. Consensus threshold was set at 80%. Two targeted literature searches were performed identifying the level of evidence of the consensus-based statements. RESULTS: Consensus was reached on 29 statements, including statements related to diagnosis and diagnostic tests, definition of response and remission, the therapy, the use of methotrexate, and tapering of treatment. The panel consented on reduction of the use of glucocorticoids to avoid side-effect, and preferred the use of biologics over conventional treatment. The role of interleukin-1 and interleukin-6 blocking agents was considered important in the treatment of AOSD. CONCLUSIONS: In this Delphi panel, a high level of consensus was achieved on recommendations for diagnosis and therapy of AOSD that can serve as a basis for a treatment guideline.

2.
BMC Immunol ; 7: 23, 2006 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-16984635

RESUMEN

BACKGROUND: The T cell attracting chemokine CCL18 is produced by antigen presenting cells and a role for CCL18 has been suggested in the pathogenesis of a variety of diseases. Rheumatoid arthritis (RA) is one of these conditions, in which abundant CCL18 production is present. Although Th2 cytokines and IL-10 are known to have an effect on CCL18 production, there are several gaps in our knowledge regarding the exact regulation of CCL18 secretion, both in general and in RA. In this study we provide new insights in the regulation of CCL18 secretion by monocytes and dendritic cells. RESULTS: In contrast to a large panel of pro-inflammatory stimuli (IL-1beta, TNF-alpha, IL-10, IL-13, IL-15, IL-17, IL-18, IFN-gamma), T cell mimicking molecules (RANKL, CD40L) or TLR driven maturation, the anti-inflammatory IL-10 strongly stimulated DC to secrete CCL18. On freshly isolated monocytes, CCL18 secretion was induced by IL-4 and IL-13, in strong synergy with IL-10. This synergistic effect could already be observed after only 24 hours, indicating that not only macrophages and dendritic cells, but also monocytes secrete CCL18 under these stimulatory conditions. A high CCL18 expression was detected in RA synovial tissue and incubation of monocytes with synovial fluid from RA patients clearly enhanced the effects of IL-4, IL-13 and IL-10. Surprisingly, the effect of synovial fluid was not driven by IL-10 of IL-13, suggesting the presence of another CCL18 inducing factor in synovial fluid. CONCLUSION: In summary, IL-10 synergistically induces CCL18 secretion in combination with IL-4 of IL-13 on monocytes and monocyte derived cells. The effects of IL-14, IL-13 and IL-10 are strongly enhanced by synovial fluid. This synergy may contribute to the high CCL18 expression in RA.


Asunto(s)
Artritis Reumatoide/inmunología , Quimiocinas CC/biosíntesis , Células Dendríticas/inmunología , Interleucinas/farmacología , Monocitos/inmunología , Líquido Sinovial/inmunología , Células Cultivadas , Citocinas/farmacología , Células Dendríticas/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Interleucina-10/farmacología , Interleucina-13/farmacología , Interleucina-4/farmacología , Monocitos/efectos de los fármacos , Receptores Toll-Like/metabolismo
3.
Neurosci Lett ; 397(1-2): 145-8, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16406320

RESUMEN

In neuro-inflammatory diseases, activated T cells are thought to drive the inflammatory process. In this study, we investigated the potential role of three T cell attracting chemokines (CK) in neuro-inflammation. For this purpose, we measured levels of CXCL16, CCL17 and CCL18 in matched serum and cerebrospinal fluid (CSF) samples of patients with different neurological diseases. Interestingly, CXCL16 levels were significantly elevated in the CSF and were higher in inflammatory disease than in controls, whereas CCL17 and CCL18 were absent in the CSF. CCL18 was only elevated in serum of SLE patients. These data suggest that attraction of activated memory type T cells by CXCL16 might play an important role in the orchestration of immune responses in the central nervous system.


Asunto(s)
Quimiocinas CXC/sangre , Quimiocinas CXC/líquido cefalorraquídeo , Inflamación/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso , Receptores Depuradores/sangre , Estudios de Casos y Controles , Quimiocina CXCL16 , Quimiocinas CC/sangre , Quimiocinas CC/líquido cefalorraquídeo , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Inflamación/sangre , Inflamación/etiología , Enfermedades del Sistema Nervioso/sangre , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/complicaciones , Linfocitos T/metabolismo
4.
J Leukoc Biol ; 77(5): 739-47, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15713699

RESUMEN

CC chemokine ligand 18/dendritic cell-chemokine 1 (CCL18/DC-CK1) is a CC chemokine, preferentially expressed by DC, which acts as a chemoattractant for naive T cells and mantle zone B cells. Applying a newly developed CCL18/DC-CK1 sandwich enzyme-linked immunosorbent assay, we demonstrate that DC secrete high amounts of CCL18/DC-CK1 and that this expression can be increased by interleukin-10. High levels of CCL18/DC-CK1 were also detected in human serum (average of 88 ng/ml). Moreover, elevated CCL18/DC-CK1 levels were detected in synovial fluid from rheumatoid arthritis patients and in drain fluid (average of 254 ng/ml and 122 ng/ml, respectively). Immunoprecipitation experiment using anti-CCL18/DC-CK1 monoclonal antibodies revealed a protein of 6-7 kDa in serum and drain fluid that was indistinguishable from recombinant CCL18/DC-CK1 on Western blot and in re-aggregation assays. The concentration of CCL18/DC-CK1 found in human serum is in the same order of magnitude as was previously reported to completely inhibit CCL11/eotaxin-induced CC chemokine receptor 3 (CCR3) activation and consequent migration of eosinophils. CCL18/DC-CK1 may therefore function as an agonist (for naive T and B cells) and as an antagonist for CCR3-expressing leukocytes such as eosinophils.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Artritis Reumatoide/inmunología , Quimiocinas CC/inmunología , Células Dendríticas/inmunología , Interleucina-10/inmunología , Especificidad de Anticuerpos , Líquidos Corporales/inmunología , Células Cultivadas , Quimiocinas CC/sangre , Quimiocinas CC/metabolismo , Quimiotaxis de Leucocito/inmunología , Ensayo de Inmunoadsorción Enzimática , Humanos , Leucocitos/inmunología , Receptores CCR3 , Receptores de Quimiocina/inmunología , Proteínas Recombinantes/inmunología
6.
Ann Rheum Dis ; 66(10): 1334-8, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17350968

RESUMEN

BACKGROUND: Antigen-presenting cells (APC) and T cells are considered to play a significant role in the pathogenesis of rheumatoid arthritis (RA). CCL18 and CXCL16 are two chemokines that facilitate T cell attraction by APC, of which a role in the pathogenesis of RA has been suggested. OBJECTIVE: To compare the circulating levels of CXCL16 and CCL18 in RA with controls and to investigate the relation of CXCL16 and CCL18 with RA disease activity and joint damage. METHODS: Circulating CCL18 and CXCL16 levels were determined in 61 RA patients with a follow-up of 6 years and a group of 41 healthy controls with ELISA. Chemokine levels were correlated with demographic data, disease activity (DAS28) and joint damage (modified Sharp score). In addition, serum CCL18 and CXCL16 levels from a cohort of 44 RA patients treated with anti-TNF-alpha were correlated with disease activity. RESULTS: CCL18 levels in serum were significantly elevated in RA patients compared with controls, while serum CXCL16 levels were not. In contrast to CXCL16, serum CCL18 was positively correlated with disease activity. Both CCL18 and CXCL16 levels decreased upon treatment with anti-TNF-alpha. Neither CCL18 nor CXCL16 correlated with joint damage and progression. CONCLUSION: Here, we show, for the first time, that circulating CCL18 and not CXCL16 levels are elevated in RA patients as compared with controls and correlate with disease activity in RA. More knowledge regarding the regulation and function of both CCL18 and CXCL16 is essential to value their role in RA.


Asunto(s)
Artritis Reumatoide/sangre , Quimiocinas CC/sangre , Quimiocinas CXC/sangre , Receptores Depuradores/sangre , Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/patología , Biomarcadores/sangre , Quimiocina CXCL16 , Femenino , Humanos , Infliximab , Articulaciones/patología , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores
7.
Biochem Biophys Res Commun ; 355(2): 392-7, 2007 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-17300746

RESUMEN

CXCL16 acts as a scavenger receptor for oxLDL in its membrane-bound form and induces migration of activated T cells in its soluble form. Due to these properties, CXCL16 has been suggested to play a role in both atherosclerosis and rheumatoid arthritis (RA). Our aim was to evaluate the contribution of soluble CXCL16 to the scavenging of oxLDL and its potential as a marker for cardiovascular disease (CVD) in patients with RA. We found that circulating CXCL16 was not correlated with plasma oxLDL or ApoB and was not related to the presence of CVD in RA patients. Moreover, CXCL16 did not bind and scavenge oxLDL in an in vitro setting. These data suggest that binding of oxLDL by soluble CXCL16 does not play a role in atherosclerosis and, although confirmation in larger studies is needed, that circulating CXCL16 is not related to the presence of CVD in patients with RA.


Asunto(s)
Artritis Reumatoide/sangre , Quimiocinas CXC/sangre , Lipoproteínas LDL/sangre , Receptores Depuradores/sangre , Adulto , Anciano , Quimiocina CXCL16 , Ensayo de Inmunoadsorción Enzimática , Humanos , Persona de Mediana Edad
8.
Cytokine ; 36(1-2): 51-6, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17166737

RESUMEN

Macrophage migration inhibitory factor (MIF) is clearly associated with rheumatoid arthritis (RA) disease severity. However, the regulation of MIF during the course of RA has not been subjected to similar scientific scrutiny. The aim of our study was to investigate the role of various Toll-like receptors (TLRs) and inflammatory mediators on MIF production by dendritic cells (DCs) in healthy controls and RA patients. DCs were cultured from 12 healthy donors and 12 RA patients. Triggering via TLR mediated pathways was achieved using various TLR specific ligands alone or in combination: Pam3Cys for TLR2, LPS and recombinant extra domain A containing fibronectin for TLR4 and Poly(I:C) and R848 for TLR3 and TLR7, respectively. In addition, iDCs from healthy controls were incubated with various cytokines, RANKL and CD40L for 48 h. MIF levels were measured using an ELISA assay. Stimulation of DCs by TLR4 ligands resulted in higher MIF production compared to immature DCs from healthy controls (p<0.002) and RA patients (p<0.002). DCs from RA patients produced higher MIF levels than healthy controls both at the immature stage (p<0.04) as well after full maturation via TLR2 (p<0.04) and TLR4 (p<0.001) triggering. Incubation with TLR3 and TLR7 ligands resulted in a significantly decreased secretion of MIF in RA patients and controls. Simultaneous incubation of TLR4 with either TLR3 or TLR7 ligands resulted in a decrease of MIF secretion when compared to TLR4 stimulation alone. The secretion of MIF increased when DCs were stimulated with TNF-alpha, RANKL and CD40L. The secretion of MIF by dendritic cells is differentially regulated by TLRs. In addition, TNF-alpha, RANKL, and CD40L augment MIF production by DCs and thus play a potential role in the amplification of the inflammatory loop in RA.


Asunto(s)
Artritis Reumatoide/metabolismo , Células Dendríticas/metabolismo , Factores Inhibidores de la Migración de Macrófagos/biosíntesis , Receptores Toll-Like/metabolismo , Femenino , Salud , Humanos , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Masculino , Transducción de Señal
9.
Arthritis Rheum ; 52(5): 1381-91, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15880344

RESUMEN

OBJECTIVE: Directional migration of leukocytes is orchestrated by the regulated expression of chemokine receptors and their ligands. The receptor CXCR6 is abundantly expressed by Th1-polarized effector/memory lymphocytes accumulating at inflammatory sites. This study was undertaken to examine the presence of CXCR6+ T cells and of CXCL16, the only ligand for CXCR6, in the joints of patients with rheumatoid arthritis (RA). METHODS: Flow cytometry analysis of the expression of CXCR6 by peripheral blood and synovial fluid (SF) T cells. In addition, by performing conventional and real-time reverse transcriptase-polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay, we determined the expression of CXCL16 and its protease ADAM-10 within synovium and by cultured macrophages. SF T cell migration was studied with the Transwell system. RESULTS: Accumulation of CXCR6+ T cells within RA SF coincided with highly elevated levels of CXCL16+ macrophages. In vitro studies revealed that monocytes started to express CXCL16 upon differentiation into macrophages, and that RA SF and tumor necrosis factor (TNF) enhanced CXCL16 expression. Moreover, RA patients responding to anti-TNF therapy showed a strongly decreased CXCL16 expression, whereas nonresponding patients did not. Interestingly, ADAM-10, a recently identified protease of CXCL16, was abundantly expressed by CXCL16+ macrophages in vitro and in RA in vivo, which resulted in increased levels of cleaved CXCL16 in RA SF relative to controls. Finally, CXCR6+ T cells from RA SF were attracted by CXCL16. CONCLUSION: These data provide evidence that enhanced production of CXCL16 in RA synovia leads to recruitment of CXCR6+ memory T cells, thereby contributing to the inflammatory cascade associated with RA pathology.


Asunto(s)
Artritis Reumatoide/inmunología , Quimiocinas CXC/biosíntesis , Macrófagos/inmunología , Proteínas de la Membrana/biosíntesis , Receptores Inmunológicos/biosíntesis , Linfocitos T/inmunología , Proteínas ADAM , Proteína ADAM10 , Secretasas de la Proteína Precursora del Amiloide , Quimiocina CXCL16 , Humanos , Memoria Inmunológica , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Metaloendopeptidasas/biosíntesis , Receptores Depuradores , Líquido Sinovial/citología , Factor de Necrosis Tumoral alfa/farmacología
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