The associations found are in agreement with biological mechanisms and clinical observations. As there is a paucity of real-life data on adverse effects of glucocorticoids prescribed to unselected groups of patients, these data may help the clinician to adapt therapy with glucocorticoids accordingly and improve the benefit-risk ratio.
The costs of illness are high in all four diseases, with a strong effect of functional status on total costs. Indirect costs differ by the factor 3, based on whether the HCA or the FCA is used.
HLA-DR(high)CD27(++)CD20(-)CD19(dim) plasmablasts represent a more precise indicator of lupus activity and suggest that there is an overproduction or lack of negative selection of these cells in SLE.
SUMMARY
Interleukin‐17 (IL‐17) has been characterized as a proinflammatory cytokine produced by CD4+ CD45RO+ memory T cells. Overproduction of IL‐17 was detected in the synovium of patients with rheumatoid arthritis (RA) compared to patients with osteoarthritis. In contrast to the restricted expression of IL‐17, the IL‐17 receptor (IL‐17R/CDw217) is expressed ubiquitously. Using a real‐time RT‐PCR assay, we detected similar absolute levels of IL‐17R mRNA expression in fibroblast‐like synoviocytes (SFC) from patients with RA (mean 9 pg/μg total RNA; ranged from 0·1 pg to 96 pg IL‐17R mRNA/μg total RNA) compared to synoviocytes of non‐RA patients. Analysis of the IL‐17R surface expression confirmed the results obtained for IL‐17R mRNA expression. Exposure of SFC to IL‐17 led to a mRNA induction of CXC chemokines IL‐8, GRO‐α and GRO‐β. An anti‐IL‐17 antibody blocked these effects of IL‐17. The MAPK p38 appears necessary for the regulation of IL‐8, GRO‐α and GRO‐β expression as shown by inhibition with SB203580. The inhibitors genistein (tyrosine kinase inhibitor) and calphostin C (inhibitor of protein kinase C) reduced significantly the IL‐17‐stimulated mRNA expression of IL‐8, GRO‐α and GRO‐β in SFC, whereas PD98059 (inhibitor of MEK‐1/2) was without effect. Pharmacological drugs used in therapy of RA, such as cyclosporin and methotrexate, induced a fourfold increase of IL‐17R mRNA expression and augmented the IL‐17‐stimulated IL‐8 expression. Our results support the hypothesis that IL‐17/IL‐17R may play a significant role in the pathogenesis of RA contributing to an unbalanced production of cytokines as well as participating in connective tissue remodelling.
The objective of this study was to evaluate glucocorticoid (GC) use in patients with polymyalgia rheumatica (PMR), giant cell arteritis (GCA) or both diseases (PMR + GCA) under rheumatological care. Data from patients with PMR (n = 1420), GCA (n = 177) or PMR + GCA (n = 261) from the National Database of the German Collaborative Arthritis Centers were analyzed regarding GCs and related comorbidities (osteoporosis, diabetes and cardiovascular disease), stratified by disease duration (DD). Longitudinal data were analyzed for all patients with a DD ≤ 2 years at database entry (n = 1397). Three-year data were available for 256 patients. Predictors of GC use ≥ 3 years were examined by logistic regression analyses. A total of 76% received GCs, and 19% (PMR) to 40% (GCA) received methotrexate. Median GC doses were 12.5 mg (PMR), 11.3 mg (GCA), and 20.0 mg/day (PMR + GCA) in a 0-6-month DD. Median GC doses ≤ 5 mg/day were reached at a 13-18-month DD in PMR patients and at a 19-24-month DD in GCA or PMR + GCA patients. In the multivariate analysis, baseline methotrexate (OR 2.03, [95% CI 1.27-3.24]), GCs > 10 mg/day (OR 1.65, [1.07-2.55]), higher disease activity (OR 1.12, [1.02-1.23]) (median 0.6 years DD), and female sex (OR 1.63 [1.09-2.43]) were predictive for GC therapy at ≥ 3 years. Of the examined comorbidities, only osteoporosis prevalence increased within 3 years. GC use for ≥ 3 years was reported in one-fourth of all the patients. A difficult-to-control disease activity within the first year was a good predictor of long-term GC need.
Background: Infections are the most common cause of late complications in cardiopulmonary bypass (CPB) surgery patients, and are difficult to predict. Here we studied the diagnostic value of a standardized immune monitoring program based on recent advances in flow cytometry (exact quantification of surfacemarker expression) and cytokine determination (semiautomatic systems).Methods: CPB patients (56) at risk for complications (age >70 years and/or preoperative left-ventricular ejection fraction < 25 %) were classified into three groups: without (33), with suspected (14), and with confirmed (9) infection. Applying the Quantibrite™-system, we daily quantified the expression of CD11b, CD64, CD71, CD86, and HLA-DR on monocytes/granulocytes. Furthermore, the ex vivo secretion of tumor necrosis factor (TNF)-␣ as well as the plasma interleukin (IL)-10 levels were determined by a semiautomatic system. Ex vivo elastase release was measured by enzyme-linked immunosorbent assay (ELISA).Results: All patients showed signs of granulocyte activation and monocyte deactivation. Monocytic HLA-DR and plasma IL-10 were the best markers to discriminate patients with infection from those without as early as day 1. Using a cutoff of 5792 HLA-DR molecules per cell, both sensitivity and negative predictive value for patients who developed microbiologically confirmed infection was 1.0, and the area under the curve (AUC) was 0.85.Conclusions: Our data suggest that a standardized immune monitoring at day 1 might be useful for early discrimination of patients at elevated risk for infections. Cytometry Part B (Clin. Cytometry) 53B:54 -62, 2003.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.