Rheumatoid Arthritis: Verbruggen G

Zhang W, Doherty M, Leeb BF, Alekseeva L, Arden NK, Bijlsma JW, Dincer F, Dziedzic K, Hauselmann HJ, Kaklamanis P, Kloppenburg M, Lohmander LS, Maheu E, Martin-Mola E, Pavelka K, Punzi L, Reiter S, Smolen J, Verbruggen G, Watt I, Zimmermann-Gorska I, Anonymous00031. · Dr W Zhang, Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, UK. · Ann Rheum Dis. · Pubmed #18250111 No free full text.

Abstract: OBJECTIVES: To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA). METHODS: The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale. RESULTS: Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR <10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint. CONCLUSION: Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.

Elewaut D, Van den Bosch F, Verbruggen G, de Keyser F, Cruyssen BV, Mielants H. · Department of Rheumatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. · Rheumatol Int. · Pubmed #18818924 No free full text.

Abstract: Spondyloarthritides (SpAs) are a cluster of chronic inflammatory rheumatic diseases that typically involve inflammation of axial and peripheral joint or tendon and ligament insertions, distinct radiographic changes and diverse extra-articular features. Conventional treatments relieve the signs and symptoms but do not prevent disease progression. TNFalpha inhibitors provide clinicians with the potential to treat the underlying pathology and to alter disease progression. By targeting the underlying inflammatory mechanisms, TNFalpha blockade can treat any extra-articular manifestations of SpA.

Verbruggen G, Wittoek R, Groeneboer S, Cruyssen BV, Goemaere S, Elewaut D. · Ghent University Hospital, Department of Rheumatology, Ghent, Belgium. · Curr Opin Rheumatol. · Pubmed #17414953 No free full text.

Abstract: PURPOSE OF REVIEW: One of the major challenges in rheumatology remains the induction of osteochondral repair in synovial joints. Remarkable progress has been made in controlling the inflammatory pathways of chronic synovitis and tissue damage in rheumatoid arthritis and spondyloarthropathy. Here, we provide an overview of the current knowledge on the mechanisms involved in osteochondral repair in degenerative joint diseases, as well as in immune mediated inflammatory arthritides, with special emphasis on tumor necrosis factor alpha and IL-1. RECENT FINDINGS: Homeostasis of articular cartilage and subchondral bone are essential for maintaining the integrity of osteochondral structures within synovial joints. This is achieved by the regulation of a delicate balance between anabolic and catabolic signals. In articular cartilage one cell type, the chondrocyte, is responsible for regulation of homeostasis. In bone, however, two distinct cell types, osteoblasts and osteoclasts, are responsible for anabolic and catabolic pathways, respectively. In inflammatory joint disorders, this tight regulation is profoundly dysregulated, with tumor necrosis factor alpha acting as an important catalyst of a disturbed homeostasis, together with IL-1. Targeting these cytokines may restore the intrinsic repair capacity of osteochondral structures. SUMMARY: To restore catabolic cytokine balances appears to be a suitable strategy to promote osteochondral repair.

Coppieters K, Dewint P, Van Beneden K, Jacques P, Seeuws S, Verbruggen G, Deforce D, Elewaut D. · Laboratory for Molecular Immunology & Inflammation, Department of Rheumatology, Ghent University Hospital, Ghent, Belgium · Rheumatology (Oxford). · Pubmed #17307755 links to  free full text

Abstract: The importance of T cell participation in the aetiology and pathogenesis of rheumatoid arthritis (RA) is now widely appreciated. The disease is mediated by activated pro-inflammatory, self-reactive T helper cells, instigating the chronic autoimmune response characteristic of rheumatoid inflammation. Natural killer T (NKT) cells are a distinctive population of T cells thought to protect self-tissues from damaging inflammatory immune responses, and are often recognized as a regulatory T cell subtype, regulating the magnitude or class of the immune response. Recently, a number of studies have provided insight concerning the role of NKT cells in different models of autoimmune joint inflammation, suggesting the involvement of this specialized T cell subset in controlling initiation and perpetuation of arthritic disease. The aim of this review is to provide rheumatologists with an introduction of the principal features of NKT cells, to give an overview of the data obtained in animal models of arthritis and to discuss the hypothesized mechanisms. Finally, we will speculate on future prospects with regard to NKT cell-targeted treatment of arthritic disease by use of glycolipids.

Verbruggen G, De Backer S, Deforce D, Demetter P, Cuvelier C, Veys E, Elewaut D. · Department of Rheumatology, University Hospital Gent, De Pintelaan 185, 9000 Gent, Belgium. · Ann Rheum Dis. · Pubmed #15564308 links to  free full text

Abstract: BACKGROUND: Much interest has been shown recently in the pathogenic role of B cells in rheumatoid arthritis (RA) owing to the marked clinical responses to anti-CD20 treatment in RA. CASE REPORT: A patient with X linked agammaglobulinaemia (XLA) presented with an erosive symmetric polyarthritis with histological features of RA, including formation of a destructive pannus. Furthermore, the patient developed subcutaneous nodules that were histologically indistinguishable from rheumatoid nodules. Surprisingly, lymphocytic infiltrates in both the synovium and nodule consisted almost exclusively of CD8+ T cells. DISCUSSION: Although some peculiar B cell subsets have been described in patients with XLA, no B cell subsets could be demonstrated in synovial tissue or the subcutaneous nodule. This case illustrates that classical RA can develop in the absence of mature B cells.

Van Beneden K, Coppieters K, Laroy W, De Keyser F, Hoffman IE, Van den Bosch F, Vander Cruyssen B, Drennan M, Jacques P, Rottiers P, Verbruggen G, Contreras R, Callewaert N, Elewaut D. · Department of Rheumatology, Laboratory of Molecular Immunology and Inflammation, Ghent University Hospital, 0K12 IB, De Pintelaan 185, B-9000 Ghent, Belgium. · Ann Rheum Dis. · Pubmed #18772190 No free full text.

Abstract: OBJECTIVES: Improved DNA sequencer-aided fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) technology was used to monitor the changes in the galactosylation status of serum immunoglobulins during the immune response and therapy of autoimmune arthritis. METHODS: Collagen-induced arthritis (CIA) was induced in susceptible DBA/1 mice and the undergalactosylation status (UGS) of serum immunoglobulins was determined using the improved DSA-FACE technology. Prophylactic intravenous tolerisation with type II collagen as well as semitherapeutic treatment with dexamethasone (DEX) were performed and UGS was analysed. Next, the serum immunoglobulin glycosylation profiles of patients with rheumatoid arthritis (RA) and spondyloarthropathy (SpA) were studied and changes in the UGS scores during anti-tumour necrosis factor (TNF)alpha therapy followed. RESULTS: In the longitudinal CIA study, the undergalactosylation state of immunoglobulins was found to be significantly correlated with the clinical arthritis scores. Upon collagen-specific tolerisation as well as glucocorticoid semitherapeutic treatment, improvement of the clinical arthritis scores correlated with decreased levels of UGS. It was also demonstrated that withdrawal of DEX was associated with an increased UGS score. Interestingly, reversibility in the UGS was also shown during treatment of patients with RA and SpA with anti-TNFalpha. CONCLUSIONS: These findings demonstrate that the UGS of serum immunoglobulins changes during the disease course of CIA and that this UGS is inhibited by antigen-specific and antigen-independent treatment procedures. The observation that Ig galactosylation is a reversible process is also documented during treatment of patients with RA and SpA with anti-TNFalpha.

Dewint P, Gossye V, De Bosscher K, Vanden Berghe W, Van Beneden K, Deforce D, Van Calenbergh S, Müller-Ladner U, Vander Cruyssen B, Verbruggen G, Haegeman G, Elewaut D. · Department of Rheumatology, Ghent University Hospital, De Pintelaan 185, Ghent, Belgium. · J Immunol. · Pubmed #18250472 links to  free full text

Abstract: The glucocorticoid receptor (GR) is a transcription factor regulating its target genes either positively, through direct binding to the promoter of target genes, or negatively by the interference with the activity of transcription factors involved in proinflammatory gene expression. The well-known adverse effects of glucocorticoids are believed to be mainly caused by their GR-mediated gene-activating properties. Although dimerization of GR is thought to be essential for gene-activating properties, no compound has yet been described which selectively imposes GR monomer formation and interference with other transcription factors. In the present study, we report on a GR-binding, plant-derived compound with marked dissociative properties in rheumatoid arthritis fibroblast-like synoviocytes, which are important effector cells in inflammation and matrix degradation in rheumatoid arthritis. In addition, these findings could be extended in vivo in murine collagen-induced arthritis, in which joint inflammation was markedly inhibited without inducing hyperinsulinemia. Therefore, we conclude that GR monomers are sufficient for inhibition of inflammation in vivo.

Baeten D, Demetter P, Cuvelier C, Van Den Bosch F, Kruithof E, Van Damme N, Verbruggen G, Mielants H, Veys EM, De Keyser F. · Department of Rheumatology, University Hospital, University of Ghent, Belgium. · Ann Rheum Dis. · Pubmed #11087697 links to  free full text

Abstract: OBJECTIVES: To compare the macroscopic and microscopic characteristics of synovial tissue in rheumatoid arthritis (RA), spondyloarthropathy (SpA), and osteoarthritis (OA) after exclusion of possible biases induced by disease duration or activity, or both. METHODS: Synovial biopsy specimens were obtained by needle arthroscopy in patients with early RA (n=16), late RA (n=14), early SpA (n=23), and OA (n=12). Macroscopic and microscopic features were scored on a four point scale and analysed as a function of disease duration (early versus late RA), local and systemic disease activity, and diagnosis. RESULTS: Except for the maximal synovial lining thickness, no significant differences were seen between early and late RA. For disease activity, synovial histology was only weakly correlated with C reactive protein in RA, but seemed to be strongly dependent on effusion of the biopsied joint in all disease groups. After stratification for local disease activity, no disease related differences were found in patients without joint effusion. In contrast, important differences were found between patients with RA and SpA with active joint effusion. Synovial vascularity was macroscopically increased in SpA versus RA (p=0.017). A straight vessel pattern was only seen in RA, while tortuous vessels were preferentially seen in SpA. Vascularity was also microscopically increased in SpA compared with RA (p=0.031), and correlated with the macroscopic vascularity (r(s)=0.36, p=0.036). CD3+ (p=0.008), CD4+ (p=0.008), and CD20+ (p=0.024) lymphocytes were overrepresented in RA compared with SpA. The integrin expression in RA was characterised by a decrease of alphaVbeta3 in the synovial lining (p=0.006) and an increase of alphaVbeta5 in the sublining (p<0.001). CONCLUSIONS: The immune architecture of the synovial membrane is more dependent on local disease activity than on disease duration. Synovium obtained from clinically affected joints shows important histological differences between RA and SpA.

Elewaut D, De Keyser F, Van den Bosch F, Verbruggen G, Veys EM. · Department of Rheumatology, University Hospital Ghent, Belgium. · Clin Exp Rheumatol. · Pubmed #10812492 No free full text.

Abstract: OBJECTIVE: The aim of the study was to evaluate the T cell receptor (TCR) family usage in T cell-lines from subcutaneous nodules and synovium from patients with rheumatoid arthritis (RA), with specific reference to the duration of symptoms. In vitro adherence characteristics of nodular T cells was studied as well. METHODS: Monoclonal antibodies were used to determine the distribution of TCR families in T cell-lines from synovium of patients with early and long-standing RA, from rheumatoid nodules and control tissues. An in vitro binding assay with T cell-lines from 2 rheumatoid nodules was performed. RESULTS: In early RA synovium, a restricted TCR family usage was observed in 5 out of 8 patients, contrary to long-standing disease, peripheral blood, ileum and colon. In RA nodules, a similar degree of restriction was noted. Moreover, the same TCR family was overexpressed by T cell-lines from different nodules derived from the same patient. T cell-lines from rheumatoid nodules demonstrated a preferential in vitro adherence to rheumatoid synovium and rheumatoid nodules, while no binding was observed on skin or tonsil. CONCLUSION: The TCR spectrum among RA synovial cell-lines broadens in relation to the disease duration. The overexpression of the same TCR family in different rheumatoid nodules from the same patients, and the in vitro adherence of T cell-lines from rheumatoid nodules may be indicative for recirculation between the different disease manifestations in RA.

Elewaut D, De Keyser F, Verbruggen G, Veys EM. · No affiliation provided · Arthritis Rheum. · Pubmed #10323470 links to  free full text

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