Rheumatoid Arthritis: Duftner C

Dejaco C, Duftner C, Wipfler E, Schirmer M. · Abteilung für Innere Medizin, Krankenhaus der Elisabethinen, Klagenfurt, Austria. · Wien Med Wochenschr. · Pubmed #19247593 No free full text.

Abstract: Abatacept is the first drug in a new class of disease-modifying anti-rheumatic drugs known as selective modulators of T-cell costimulation. The efficacy of abatacept in the treatment of rheumatoid arthritis (RA) has been shown in several clinical phase II and phase III trials, wherein abatacept was used in monotherapy, either in combination with methotrexate (MTX) after MTX-failure, in combination with MTX after failure of anti-TNF-alpha therapy or in combination with TNF-alpha blockers. In addition, the combination of abatacept/MTX was directly compared with infliximab/MTX. Current data on abatacept demonstrate an encouraging safety profile of this drug. The number of adverse events in patients on abatacept is comparable to that in patients treated with other biologics. Severe infections, however, are more common in abatacept-treated patients than in placebo-treated patients. Opportunistic infections are rare in patients with abatacept and the frequency of malignancies is not higher than expected in RA-patients. Additional studies are now warranted to get more information on rare adverse events and long-term unwanted effects.

Klauser AS, Moriggl B, Duftner C, Smekal V, Pallwein L, Mur E, Schirmer M. · Universitätsklinik für Radiodiagnostik, Klinische Abteilung für Radiodiagnostik II, Medizinische Universität Innsbruck, Anichstrasse 35, 6020 Innsbruck, Osterreich. · Radiologe. · Pubmed #16715223 No free full text.

Abstract: High-frequency sonography enables excellent detection of early erosions and synovial proliferations. Power Doppler sonography (PDUS) allows for an improved characterization of articular and peritendinous augmented volume, because detection of hypervascularity correlates with inflammatory activity and further is helpful in differentiation from effusion and inactive pannus. The use of contrast media improves the sensitivity of vascularity detection, because they allow for a delineation of vessels at the microvascular level. This is of increased interest, as the development of new therapeutic options targeting the microvascular level calls for earlier diagnosis and optimal assessment of disease activity. Because of good availability, cost effectiveness, and patient acceptance, sonography facilitates early diagnosis of synovial proliferations and erosions as well as therapy follow-up.

Klauser AS, Wipfler E, Dejaco C, Moriggl B, Duftner C, Schirmer M. · Clinical Department of Radiology II, Innsbruck Medical University, Innsbruck, Austria. · Clin Exp Rheumatol. · Pubmed #18799083 No free full text.

Abstract: OBJECTIVE: To examine the diagnostic values of history of chronic enthesitic pain and clinical signs of acutely inflamed entheses to predict ultrasound (US) signs of enthesitis. METHODS: Cohort study of 21 consecutive rheumatic out-patients (female/male 18/3) with suspected multiple enthesitis and 12 controls (female/male 10/2). 429 enthesal sites according to the Maastricht Ankylosing Spondylitis Entheses Score (MASES) were evaluated by history, clinical examination, B-mode and power Doppler US. Sensitivity and specificity of history suggesting chronic enthesitic pain and clinical examination suggesting acute enthesitis were calculated using corresponding US findings as reference standard. RESULTS: Diagnostic accuracy widely varied between different MASES sites. Sensitivity and specificity of selected MASES points were 66.7 - 86.4% and 85.0 - 91.7% for history and 71.4 - 87.0% and 47.4 - 75.0% for clinical examination, respectively (p<0.05 for each). CONCLUSION: At specific enthesal sites, history of chronic enthesitic pain and clinical signs of acute inflammation are sensitive and specific for the diagnosis of chronic and/or acute inflammation.

Prelog M, Schwarzenbrunner N, Sailer-Höck M, Kern H, Klein-Franke A, Ausserlechner MJ, Koppelstaetter C, Brunner A, Duftner C, Dejaco C, Strasak AM, Müller T, Zimmerhackl LB, Brunner J. · Department of Pediatrics, Medical University Innsbruck, Innsbruck, Austria. · Arthritis Rheum. · Pubmed #18576332 links to  free full text

Abstract: OBJECTIVE: Juvenile idiopathic arthritis (JIA) is an autoimmune disease of the young. The pathogenesis is not completely understood. Premature aging, associated thymic involution, and compensatory autoproliferation could play important roles in the pathogenesis of autoimmunity. We undertook this study to determine whether patients with JIA demonstrate premature immunosenescence. METHODS: To test this hypothesis, we measured 3 indicators of aging: the percentages and total counts of peripheral blood naive T cells, the frequency of T cell receptor excision circles (TRECs) in naive T cells, and telomeric erosion and Ki-67 expression as estimates of the replicative history of homeostatic proliferation. RESULTS: JIA patients showed an accelerated loss of CD4+,CD45RA+,CD62L+ naive T cells with advancing age and a compensatory increase in the number of CD4+,CD45RO+ memory T cells. JIA patients demonstrated a significantly decreased frequency of TRECs in CD4+,CD45RA+ naive T cells compared with age-matched healthy donors (P = 0.002). TREC numbers correlated with age only in healthy donors (P = 0.0001). Telomeric erosion in CD4+,CD45RA+ naive T cells was increased in JIA patients (P = 0.01). The percentages of Ki-67-positive CD4+,CD45RA+ naive T cells were increased in JIA patients (P = 0.001) and correlated with disease duration (P = 0.003), which was also an independent factor contributing to telomeric erosion (P = 0.04). CONCLUSION: Our findings suggest that age-inappropriate T cell senescence and disturbed T cell homeostasis may contribute to the development of JIA. In patients with JIA, dysfunction in the ability to reconstitute the T cell compartment should be considered when exploring new therapeutic strategies.

Duftner C, Dejaco C, Larcher H, Schirmer M, Herold M. · Clinical Department of Internal Medicine, Division of General Internal Medicine, Innsbruck Medical University, Innsbruck, Austria. · Rheumatol Int. · Pubmed #18504584 No free full text.

Abstract: The efficacy of biological agents has been shown in several randomized clinical trials. However, little is known regarding the performance of these drugs in daily rheumatological care. Totally, 173 patients treated with biological agents (infliximab, etanercept, adalimumab, anakinra) were retrospectively analyzed between November 2001 and December 2005 at an Austrian rheumatic outpatient clinic. In total, 224 courses of treatment with biological agents were followed up. Among the 93 drug discontinuations observed, the most frequent causes were inefficacy (56.5%) and side effects (31.9%). In 74 patients (51%), the first biological agent was withdrawn after a median treatment period of 10.7 (range 0-80) months. A second biological agent was given to 36 patients, a third to 11 and a fourth to 3 patients. Our data underline the necessity of large observational studies to assess the full spectrum of patients treated with biological agents in clinical routine.

Langegger C, Wenger M, Duftner C, Dejaco C, Baldissera I, Moncayo R, Schirmer M. · Clinical Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. · Rheumatol Int. · Pubmed #17252265 No free full text.

Abstract: This study was conducted to assess the use of the European preliminary criteria, the Breiman-classification tree and the American-European criteria for diagnosis of primary Sjögren's Syndrome (pSS) in daily practice. A retrospective analysis of 17 consecutive patients with pSS (European criteria) was performed evaluating the application of the Schirmer test, semiquantitative sialoscintigraphy, immunologic tests, including rheumatoid factor, antinuclear antibodies, Sjögren's syndrome autoantibodies (SS-A, SS-B) and lip biopsy. Out of the 17 patients with pSS according to the European criteria, 15 patients fulfilled the classification tree (=88.2%), and 4 patients fulfilled the American-European criteria (=23.5%, P = 0.001). In the four patients fulfilling the American-European criteria, a positive result of the sialoscintigraphy was not crucial for the diagnosis according to these criteria. In conclusion, the American-European criteria are more stringent than the European preliminary criteria. We assume the role of sialoscintigraphy to be reduced when applying the American-European criteria.

Dejaco C, Klotz W, Larcher H, Duftner C, Schirmer M, Herold M. · Clinical Department of Internal Medicine, Division of General Internal Medicine, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. · Arthritis Res Ther. · Pubmed #16859519 links to  free full text

Abstract: Antibodies directed against citrullinated vimentin are members of the family of autoantibodies reactive with citrullinated proteins and are among the most specific serological markers for the diagnosis of rheumatoid arthritis (RA). This study was performed to test the diagnostic value of a newly developed enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against a genetically modified citrullinated vimentin (anti-MCV) in comparison with a second-generation anti-cyclic citrullinated peptides (anti-CCP2) ELISA test system. Blinded sera from 631 patients (409 consecutive out-patients and 222 randomly selected stored sera) with RA (n = 164) and non-RA (osteoarthritis [n = 120], polymyalgia rheumatica/giant cell arteritis [n = 80], spondyloarthritis [n = 36], and other inflammatory rheumatic or non-inflammatory disease [n = 67]) were tested for the presence of anti-MCV and anti-CCP2 antibodies according to the manufacturers' instructions. The diagnostic performance of the anti-MCV was comparable with the anti-CCP2 assay for the diagnosis of RA according to the calculated area under the curve (0.824; 95% confidence interval (CI) 0.778-0.870 versus 0.818; 95% CI 0.767-0.869) as analysed by receiving operating characteristic curve. When categorised with a cutoff value of 20.0 U/ml (as recommended by the manufacturer), sensitivity and specificity of the anti-MCV ELISA were 69.5% (95% CI 61.9%-76.5%) and 90.8% (86.9%-93.8%), respectively, compared with 70.1% (62.5%-77.0%) and 98.7% (96.7%-99.6%) of the anti-CCP2 assay. Using the cutoff values of 19.0 U/ml and 81.5 U/ml for the anti-MCV test to obtain a sensitivity and specificity identical to the anti-CCP2 assay, showed a reduced specificity (89.8%; 85.8%-92.9%) and sensitivity (53.7%; 45.7%-61.5%), respectively, of the anti-MCV ELISA compared with the anti-CCP2 test. In conclusion, the serum ELISA testing for anti-MCV antibodies as well as the anti-CCP-2 assay perform comparably well in the diagnosis of RA. In the high-specificity range, however, the anti-CCP2 assay appears to be superior to the anti-MCV test.

Raffeiner B, Dejaco C, Duftner C, Kullich W, Goldberger C, Vega SC, Keller M, Grubeck-Loebenstein B, Schirmer M. · Department of Internal Medicine, Innsbruck Medical University, Austria. · Arthritis Res Ther. · Pubmed #16277694 links to  free full text

Abstract: CD3+CD4+CD28null and CD3+CD8+CD28null T cells are enriched in patients with immune-mediated diseases compared with healthy controls. This study shows that CD4+CD28null T cells express Toll-like receptors recognizing bacterial lipopolysaccharides in ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis. In ankylosing spondylitis, TLR4 (23.1 +/- 21.9%) and, to a smaller extent, TLR2 (4.1 +/- 5.8%) were expressed on CD4+CD28null T cells, whereas expression was negligible on CD4+CD28+ and CD8+ T cells. CD4+CD28null T cells produced perforin upon stimulation with lipopolysaccharide, and this effect was enhanced by autologous serum or recombinant soluble CD14. Perforin production could be prevented with blocking antibodies directed against CD14 or TLR4. Incubation of peripheral blood mononuclear cells with tumour necrosis factor alpha led to an upregulation of TLR4 and TLR2 on CD4+CD28null T cells in vitro, and treatment of patients with antibodies specifically directed against tumour necrosis factor alpha resulted in decreased expression of TLR4 and TLR2 on CD4+CD28null T cells in vivo. We describe here a new pathway for direct activation of cytotoxic CD4+ T cells by components of infectious pathogens. This finding supports the hypothesis that CD4+CD28null T cells represent an immunological link between the innate immune system and the adaptive immune system.

Schroecksnadel K, Winkler C, Duftner C, Wirleitner B, Schirmer M, Fuchs D. · Division of Biological Chemistry, Biocentre Fritz, Innsbruck Medical University, Pregl Strasse 3, 6020 Innsbruck, Austria. · Clin Rheumatol. · Pubmed #16261283 No free full text.

Abstract: Immune system activation is known to be involved in the progression of rheumatoid arthritis (RA). The proinflammatory cytokine interferon-gamma in various cells, including monocytes, induces the enzyme indoleamine (2,3)-dioxygenase (IDO), which converts tryptophan to kynurenine. In sera of 22 patients (17 women and 5 men) with RA stages 1 to 4 according to Steinbrocker, the concentrations of tryptophan and kynurenine were measured by high-pressure liquid chromatography. To estimate IDO activity, the kynurenine to tryptophan ratio (kyn/trp) was calculated. In parallel, concentrations of the macrophage activation marker neopterin were determined by enzyme-linked immunosorbent assay. Tryptophan concentrations were lower in patients with RA, and the decrease in serum tryptophan correlated with increase in stage (p<0.05). Kyn/trp correlated well with neopterin concentrations, which were elevated in most patients. Whereas higher C-reactive protein concentrations and erythrocyte sedimentation rates were observed in patients with greater disease activity, tryptophan and neopterin concentrations did not differ between patients with different subjective disease activity graded by the physician. Deficiency of the essential amino acid tryptophan in patients with RA most likely results from immune activation involved in the pathogenesis of the disease. It could also be relevant for the mood of patients, as tryptophan is the precursor of serotonin.

Dejaco C, Duftner C, Klotz W, Schirmer M, Herold M. · No affiliation provided · Scand J Rheumatol. · Pubmed #18759163 No free full text.

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