title: The impact of DMARD and anti-TNF therapy on functional characterization of short-term T-cell activation in patients with rheumatoid arthritis--a follow-up study.
abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a systemic dysfunction of T-cells. In this study we tested the impact of DMARD and anti-TNF agents on short-term activation characteristics of T-cells. We enrolled 12 patients with newly diagnosed RA (naïve RA) who were treated with methothrexate (MTX) and glucocorticsteroid (GCS) and 22 patients with established RA non responding to conventional DMARD therapy who were treated with different anti-TNF agents. Nine healthy volunteers served as controls. Blood samples were taken at baseline, then at 4th and 8th week of therapy. The characteristics of several intracellular activation processes during short-term activation of T-cells including cytoplasmic Ca(2+) level, mitochondrial Ca(2+) level, reactive oxygen species (ROS) and nitric oxide (NO) generation were determined by a novel flow-cytometry technique. At baseline, the tested processes were comparable to controls in naïve RA. During GCS therapy, cytoplasmic Ca(2+) level and ROS generation decreased. After the addition of MTX to GCS cytoplasmic Ca(2+) level became comparable to controls, while ROS generation decreased further. In DMARD non responders, cytoplasmic Ca(2+) level was higher than controls at baseline. The cytoplasmic Ca(2+) level became comparable to controls and ROS generation decreased during each of the three anti-TNF-α agent therapies. Mitochondrial Ca(2+) level and NO generation were unaltered in all of the patient groups. These results indicate that intracellular machinery is affected in T-cells of RA patients. This may alter the behavior of T-cells during activation. Different therapeutic approaches may modulate the abnormal T-cell functions.
authors.affiliation: Department of Laboratory Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Szalay
authors.affiliation: First Department of Pediatrics, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Aron
authors.initials: A
authors.lastname: Cseh
authors.affiliation: First Department of Pediatrics, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Gergő
authors.initials: G
authors.lastname: Mészáros
authors.affiliation: Department of Rheumatology, Faculty of Medicine, Albert Szent-Györgyi Health Center, University of Szeged, Szeged, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Kovács
authors.affiliation: Department of Rheumatology, Faculty of Medicine, Albert Szent-Györgyi Health Center, University of Szeged, Szeged, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Balog
authors.affiliation: Department of Laboratory Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary; MTA-SE, Pediatrics and Nephrology Research Group, Budapest, Hungary.
authors.forename: Barna
authors.initials: B
authors.lastname: Vásárhelyi
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002118:Calcium / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009569:Nitric Oxide / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D018501:Antirheumatic Agents; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002118:Calcium; D008727:Methotrexate
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