The pronounced Th17 profile in systemic sclerosis (SSc) together with intracellular expression of TGFbeta and IFNgamma distinguishes SSc phenotypesTimothy R D J Radstake
Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
PLoS ONE 4:e5903. 2009
..Systemic sclerosis (SSc) is an autoimmune disease where controversy on Th1/Th2 balance dominates. We investigated whether the recently discovered Th17 pattern was present in SSc...
- Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus
Timothy R D J Radstake
Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Nat Genet 42:426-9. 2010
..39 x 10(-9) in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 x 10(-18)), IRF5 (P = 1.86 x 10(-13)) and STAT4 (P = 3.37 x 10(-9)) gene regions as SSc genetic risk factors...
TLR2 promotes Th2/Th17 responses via TLR4 and TLR7/8 by abrogating the type I IFN amplification loopMark H Wenink
Department of Rheumatology, Radboud University Nijmegen Medical Center, Geert Grooteplein 8, 6500 HB Nijmegen, The Netherlands
J Immunol 183:6960-70. 2009
..This shift in T cell responses was inherent to the inability of TLR2-stimulated DCs to produce IL-12p70 and was dependent on the production of IL-1 and IL-6...
- Macrophage migration inhibitory factor polymorphisms do not predict therapeutic response to glucocorticoids or to tumour necrosis factor alpha-neutralising treatments in rheumatoid arthritis
Timothy R D J Radstake
Department of Rheumatology, Experimental Rheumatology and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, PO 6525 GA, Nijmegen, The Netherlands
Ann Rheum Dis 66:1525-30. 2007
..Therefore, the question of whether two functional variants in MIF are associated with the response to tumour necrosis factor (TNF)alpha-neutralising and GC treatments in RA was investigated...
The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid arthritisMieke F Roelofs
Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
J Rheumatol 35:558-61. 2008
..To investigate functional consequences of the Toll-like receptor 4 (TLR4) variant (Asp299Gly) in rheumatoid arthritis (RA)...
- Circulating leptin and adiponectin concentrations during tumor necrosis factor blockade in patients with active rheumatoid arthritis
Calin Popa
Department of Rheumatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
J Rheumatol 36:724-30. 2009
..We investigated the effects of longterm therapeutic tumor necrosis factor (TNF) blockade on adipocytokine concentrations in patients with RA...
- The functional variant of the inhibitory Fcgamma receptor IIb (CD32B) is associated with the rate of radiologic joint damage and dendritic cell function in rheumatoid arthritis
Timothy R D J Radstake
Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Arthritis Rheum 54:3828-37. 2006
..The purpose of this study was to unravel the role of the inhibitory FcgammaRIIb in rheumatoid arthritis (RA) by studying the effect of the FCGR2B 695T>C polymorphism on susceptibility to RA, severity of the disease, and DC function...
- Increased frequency and compromised function of T regulatory cells in systemic sclerosis (SSc) is related to a diminished CD69 and TGFbeta expression
Timothy R D J Radstake
Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
PLoS ONE 4:e5981. 2009
..Regulatory T cells (Tregs) are essential in the control of tolerance. Evidence implicates Tregs in human autoimmune conditions. Here we investigated their role in systemic sclerosis (SSc)...
- Novel insights in the regulation of CCL18 secretion by monocytes and dendritic cells via cytokines, toll-like receptors and rheumatoid synovial fluid
Antoine W T van Lieshout
Department of Rheumatology, Radboud University Nijmegen Medical Centre, The Netherlands
BMC Immunol 7:23. 2006
..In this study we provide new insights in the regulation of CCL18 secretion by monocytes and dendritic cells...
- Modulation of lipoprotein plasma concentrations during long-term anti-TNF therapy in patients with active rheumatoid arthritis
Calin Popa
Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Ann Rheum Dis 66:1503-7. 2007
..In the present study, we investigated the effects of 1-year therapy with anti-TNF on the lipid profile of RA patients...
- The inhibitory Fc gamma IIb receptor dampens TLR4-mediated immune responses and is selectively up-regulated on dendritic cells from rheumatoid arthritis patients with quiescent disease
Mark H Wenink
Department of Rheumatology, Nijmegen Centre of Molecular Life Sciences and Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, Nijmegen 6500 HB, The Netherlands
J Immunol 183:4509-20. 2009
..This TLR4-FcgammaRIIb interaction was shown to dependent on the PI3K and Akt pathway...
- MIF production by dendritic cells is differentially regulated by Toll-like receptors and increased during rheumatoid arthritis
Calin Popa
Department of Rheumatology, Radboud University Nijmegen Medical Centre, P O Box 9101, 6500 HB Nijmegen, The Netherlands
Cytokine 36:51-6. 2006
..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...
- HMOX1 promoter polymorphism modulates the relationship between disease activity and joint damage in rheumatoid arthritis
Frank A D T G Wagener
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Arthritis Rheum 58:3388-93. 2008
..The aim of this study was to determine whether the (GT)n-repeat length within the HMOX1 promoter region is associated with RA disease severity and radiographic joint damage...
- Pharmacogenetics of anti-TNF treatment in patients with rheumatoid arthritis
Marieke J H Coenen
Radboud University, Nijmegen Medical Centre, Department of Human Genetics, Internal Mail 855, PO Box 9101, 6500 HB, Nijmegen, The Netherlands
Pharmacogenomics 8:761-73. 2007
..Nevertheless, replication and large prospective studies will be needed to demonstrate the validity of the identified genetic markers before implementation into daily clinical practice...
- The functional polymorphism 844 A>G in FcαRI (CD89) does not contribute to systemic sclerosis or rheumatoid arthritis susceptibility
Jasper C A Broen
Department of Rheumatology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
J Rheumatol 38:446-9. 2011
..To investigate the role of the Fc(α)RI 844 A>G functional polymorphism in the genetic predisposition to rheumatoid arthritis (RA) and systemic sclerosis (SSc) susceptibility...
- Circulating levels of the chemokine CCL18 but not CXCL16 are elevated and correlate with disease activity in rheumatoid arthritis
Antoine W T van Lieshout
Department of Rheumatology, Radboud University Nijmegen Medical Centre, The Netherlands
Ann Rheum Dis 66:1334-8. 2007
..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...
- Expression of toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation by proinflammatory cytokines interleukin-12 and interleukin-18 via interferon-gamma
Timothy R D J Radstake
University Medical Center Nijmegen, Nijmegen, The Netherlands
Arthritis Rheum 50:3856-65. 2004
..The synergistic effect of IL-12 and IL-18 on T cell IFNgamma production seems to regulate expression of TLR-2 and TLR-4 in the synovial tissue of RA patients...
- The -2518A>G promoter polymorphism in the CCL2 gene is not associated with systemic sclerosis susceptibility or phenotype: results from a multicenter study of European Caucasian patients
Timothy R D J Radstake
Department of Rheumatology, Radboud University, Nijmegen Medical Centre, The Netherlands
Hum Immunol 70:130-3. 2009
..Our results demonstrate that the functional variant -2518A>G of CCL2 is not implicated in the susceptibility or phenotype of SSc...
- Inhibition of Toll-like receptor 4 breaks the inflammatory loop in autoimmune destructive arthritis
Shahla Abdollahi-Roodsaz
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Arthritis Rheum 56:2957-67. 2007
..The objective of this study was to investigate the involvement of TLR-4 activation in the development and progression of autoimmune destructive arthritis...
- Common and different genetic background for rheumatoid arthritis and coeliac disease
Marieke J H Coenen
Department of Human Genetics, Institute for Genetic and Metabolic Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Hum Mol Genet 18:4195-203. 2009
..We confirmed two known loci and identified four novel ones for shared CD-RA genetic risk. Most of the shared loci further emphasize a role for adaptive and innate immunity in these diseases...
- Genetic variants in toll-like receptors are not associated with rheumatoid arthritis susceptibility or anti-tumour necrosis factor treatment outcome
Marieke J H Coenen
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Institute for Genetic and Metabolic Disease IGMD, Nijmegen, The Netherlands
PLoS ONE 5:e14326. 2010
..We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication...
- Circulating CXCL16 is not related to circulating oxLDL in patients with rheumatoid arthritis
Antoine W T van Lieshout
Department of Rheumatology, Radboud University Nijmegen Medical Centre and Nijmegen Centre of Molecular Life Sciences, The Netherlands
Biochem Biophys Res Commun 355:392-7. 2007
..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...
- Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis
Shahla Abdollahi-Roodsaz
Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
J Clin Invest 118:205-16. 2008
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- CXCL16 is elevated in the cerebrospinal fluid versus serum and in inflammatory conditions with suspected and proved central nervous system involvement
Linda M P le Blanc
Department of Rheumatology, Radboud University Nijmegen Medical Centre, The Netherlands
Neurosci Lett 397:145-8. 2006
..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...
- Correlation of rheumatoid arthritis severity with the genetic functional variants and circulating levels of macrophage migration inhibitory factor
Timothy R D J Radstake
Department of Rheumatology, Experimental Rheumatology and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Arthritis Rheum 52:3020-9. 2005
..To study whether genetic variants of macrophage migration inhibitory factor (MIF), the MIF -173G>C and CATT(5-8) alleles, are associated with disease severity and levels of circulating MIF in patients with rheumatoid arthritis (RA)...
- Impaired dendritic cell proinflammatory cytokine production in psoriatic arthritis
Mark H Wenink
Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Arthritis Rheum 63:3313-22. 2011
..We undertook this study to determine whether an impaired acute inflammatory response by dendritic cells (DCs) might compromise the clearance of bacteria and predispose to chronic inflammation...
- Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci
Alexandra Zhernakova
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
PLoS Genet 7:e1002004. 2011
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- Validation study of existing gene expression signatures for anti-TNF treatment in patients with rheumatoid arthritis
Erik J M Toonen
Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
PLoS ONE 7:e33199. 2012
..Our results confirm that gene expression profiling prior to treatment is a useful tool to predict anti-TNF (non) response...
- The orchestra of Toll-like receptors and their potential role in frequently occurring rheumatic conditions
Mieke F Roelofs
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Arthritis Rheum 58:338-48. 2008
- Skewed X chromosomal inactivation impacts T regulatory cell function in systemic sclerosis
Jasper C A Broen
Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Ann Rheum Dis 69:2213-6. 2010
..To investigate the role of X chromosomal inactivation (XCI) in systemic sclerosis (SSc) and its effects on forkhead box P3 (Foxp3) expression in T regulatory cells (Tregs)...
- Local IL-13 gene transfer prior to immune-complex arthritis inhibits chondrocyte death and matrix-metalloproteinase-mediated cartilage matrix degradation despite enhanced joint inflammation
Karin C A M Nabbe
Department of Experimental Rheumatology and Advanced Therapeutics, University Medical Center Nijmegen, Nijmegen, The Netherlands
Arthritis Res Ther 7:R392-401. 2005
..This study demonstrates that IL-13 overexpression during ICA diminished both chondrocyte death and MMP-mediated VDIPEN expression, even though joint inflammation was enhanced...
- Elevated CXCL16 expression by synovial macrophages recruits memory T cells into rheumatoid joints
Robbert van der Voort
Nijmegen Center for Molecular Life Sciences, University Medical Center St. Radboud, Nijmegen, The Netherlands
Arthritis Rheum 52:1381-91. 2005
..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...
- Deciphering the genetic background of systemic sclerosis
Jasper C A Broen
Department of Rheumatology, Radboud University Medical Centre, Nijmegen, The Netherlands
Expert Rev Clin Immunol 7:449-62. 2011
..We discuss indicators for a genetic component present in SSc, family studies, chromosomal aberrances, the involvement of the HLA region and multiple candidate genes and, finally, genome-wide association studies...
- Cytokine and chemokine production by human pancreatic islets upon enterovirus infection
Barbara M Schulte
1Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Diabetes 61:2030-6. 2012
..Our data represent the first comprehensive overview of inflammatory mediators that are secreted by human islets of Langerhans upon CVB infection and may shed light on the role of enteroviruses in type 1 diabetes pathogenesis...
- Genetics of systemic sclerosis: an update
Jasper C A Broen
Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Curr Rheumatol Rep 14:11-21. 2012
..This year has been of particular interest due to the publication of a large genome-wide association study, further investigations into gene-gene interactions, and the tendency to validate genetic results in functional models...
- The Toll-like receptor 4 Asp299Gly functional variant is associated with decreased rheumatoid arthritis disease susceptibility but does not influence disease severity and/or outcome
Timothy R D J Radstake
University Medical Center Nijmegen, Nijmegen, The Netherlands
Arthritis Rheum 50:999-1001. 2004
- Role of Fcgamma receptors IIA, IIIA, and IIIB in susceptibility to rheumatoid arthritis
Timothy R D J Radstake
Department of Rheumatology, University Medical Centre St Radboud, Nijmegen, The Netherlands
J Rheumatol 30:926-33. 2003
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