TY - JOUR A1 - Bittner, Stefan A1 - Bobak, Nicole A1 - Feuchtenberger, Martin A1 - Herrmann, Alexander M A1 - Göbel, Kerstin A1 - Kinne, Raimund W A1 - Hansen, Anker J A1 - Budde, Thomas A1 - Kleinschnitz, Christoph A1 - Frey, Oliver A1 - Tony, Hans-Peter A1 - Wiendl, Heinz A1 - Meuth, Sven G T1 - Expression of K\(_2\)\(_P\)5.1 potassium channels on CD4\(^+\)T lymphocytes correlates with disease activity in rheumatoid arthritis patients JF - Arthritis Research & Therapy N2 - Introduction CD4+ T cells express K2P5.1 (TWIK-related acid-sensitive potassium channel 2 (TASK2); KCNK5), a member of the two-pore domain potassium channel family, which has been shown to influence T cell effector functions. Recently, it was shown that K2P5.1 is upregulated upon (autoimmune) T cell stimulation. The aim of this study was to correlate expression levels of K2P5.1 on T cells from patients with rheumatoid arthritis (RA) to disease activity in these patients. Methods Expression levels of K2P5.1 were measured by RT-PCR in the peripheral blood of 58 patients with RA and correlated with disease activity parameters (C-reactive protein levels, erythrocyte sedimentation rates, disease activity score (DAS28) scores). Twenty patients undergoing therapy change were followed-up for six months. Additionally, synovial fluid and synovial biopsies were investigated for T lymphocytes expressing K2P5.1. Results K2P5.1 expression levels in CD4+ T cells show a strong correlation to DAS28 scores in RA patients. Similar correlations were found for serological inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein). In addition, K2P5.1 expression levels of synovial fluid-derived T cells are higher compared to peripheral blood T cells. Prospective data in individual patients show a parallel behaviour of K2P5.1 expression to disease activity parameters during a longitudinal follow-up for six months. Conclusions Disease activity in RA patients correlates strongly with K2P5.1 expression levels in CD4+ T lymphocytes in the peripheral blood in cross-sectional as well as in longitudinal observations. Further studies are needed to investigate the exact pathophysiological mechanisms and to evaluate the possible use of K2P5.1 as a potential biomarker for disease activity and differential diagnosis. KW - neurology Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139334 VL - 13 IS - R21 ER - TY - JOUR A1 - Tony, Hans-Peter A1 - Burmester, Gerd A1 - Schulze-Koops, Hendrik A1 - Grunke, Mathias A1 - Henes, Joerg A1 - Kötter, Ina A1 - Haas, Judith A1 - Unger, Leonore A1 - Lovric, Svjetlana A1 - Haubitz, Marion A1 - Fischer-Betz, Rebecca A1 - Chehab, Gamal A1 - Rubbert-Roth, Andrea A1 - Specker, Christof A1 - Weinerth, Jutta A1 - Holle, Julia A1 - Müller-Ladner, Ulf A1 - König, Ramona A1 - Fiehn, Christoph A1 - Burgwinkel, Philip A1 - Budde, Klemens A1 - Sörensen, Helmut A1 - Meurer, Michael A1 - Aringer, Martin A1 - Kieseier, Bernd A1 - Erfurt-Berge, Cornelia A1 - Sticherling, Michael A1 - Veelken, Roland A1 - Ziemann, Ulf A1 - Strutz, Frank A1 - von Wussow, Praxis A1 - Meier, Florian MP A1 - Hunzelmann, Nico A1 - Schmidt, Enno A1 - Bergner, Raoul A1 - Schwarting, Andreas A1 - Eming, Rüdiger A1 - Schwarz-Eywill, Michael A1 - Wassenberg, Siegfried A1 - Fleck, Martin A1 - Metzler, Claudia A1 - Zettl, Uwe A1 - Westphal, Jens A1 - Heitmann, Stefan A1 - Herzog, Anna L. A1 - Wiendl, Heinz A1 - Jakob, Waltraud A1 - Schmidt, Elvira A1 - Freivogel, Klaus A1 - Dörner, Thomas A1 - Hertl, Michael A1 - Stadler, Rudolf T1 - Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID) JF - Arthritis Research & Therapy N2 - Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin’s lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician’s visual analogue scale; mean improvement from baseline of 12.1 mm) KW - GRAID Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142856 VL - 13 IS - R75 ER -