TRAIL Death Receptor-4, Decoy Receptor-1 and Decoy Receptor-2 Expression on CD8+ T Cells Correlate with the Disease Severity in Patients with Rheumatoid Arthritis

BACKGROUND: Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disorder. Although the pathogenesis of disease is unclear, it is well known that T cells play a major role in both development and perpetuation of RA through activating macrophages and B cells. Since the lack of TNF-Related Apoptosis Inducing Ligand (TRAIL) expression resulted in defective thymocyte apoptosis leading to an autoimmune disease, we explored evidence for alterations in TRAIL/TRAIL receptor expression on peripheral T lymphocytes in the molecular mechanism of RA development. METHODS: The expression of TRAIL/TRAIL receptors on T cells in 20 RA patients and 12 control individuals were analyzed using flow cytometry. The correlation of TRAIL and its receptor expression profile was compared with clinical RA parameters (RA activity scored as per DAS28) using Spearman Rho Analysis. RESULTS: While no change was detected in the ratio of CD4+ to CD8+ T cells between controls and RA patient groups, upregulation of TRAIL and its receptors (both death and decoy) was detected on both CD4+ and CD8+ T cells in RA patients compared to control individuals. Death Receptor-4 (DR4) and the decoy receptors DcR1 and DcR2 on CD8+ T cells, but not on CD4+ T cells, were positively correlated with patients' DAS scores. CONCLUSIONS: Our data suggest that TRAIL/TRAIL receptor expression profiles on T cells might be important in revelation of RA pathogenesis

TRAIL Death Receptor-4, Decoy Receptor-1 and Decoy Receptor-2 Expression on CD8⁺T Cells Correlate with the Disease Severity in Patients with Rheumatoid Arthritis

Abstract Background Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disorder. Although the pathogenesis of disease is unclear, it is well known that T cells play a major role in both development and perpetuation of RA through activating macrophages and B cells. Since the lack of TNF-Related Apoptosis Inducing Ligand (TRAIL) expression resulted in defective thymocyte apoptosis leading to an autoimmune disease, we explored evidence for alterations in TRAIL/TRAIL receptor expression on peripheral T lymphocytes in the molecular mechanism of RA development. Methods The expression of TRAIL/TRAIL receptors on T cells in 20 RA patients and 12 control individuals were analyzed using flow cytometry. The correlation of TRAIL and its receptor expression profile was compared with clinical RA parameters (RA activity scored as per DAS28) using Spearman Rho Analysis. Results While no change was detected in the ratio of CD4+ to CD8+ T cells between controls and RA patient groups, upregulation of TRAIL and its receptors (both death and decoy) was detected on both CD4+ and CD8+ T cells in RA patients compared to control individuals. Death Receptor-4 (DR4) and the decoy receptors DcR1 and DcR2 on CD8+ T cells, but not on CD4+ T cells, were positively correlated with patients' DAS scores. Conclusions Our data suggest that TRAIL/TRAIL receptor expression profiles on T cells might be important in revelation of RA pathogenesis.</p

nonthrombotic Behcet's patients

Objective: The aim of this study was to compare plasma Platelet-activating factor (PAF) and P-selectin (CD62P) activities in Behcet's disease patients with and without thrombosis. Methods: In this cross-sectional and descriptive study, 30 consecutive Behcet's patients were included, 15 of them with venous thrombosis. All patients were also divided into two subgroups according to the presence or absence of clinical activity. Plasma PAF levels, basal and Ca++ ionophore (A23187)-induced leukocyte (cellular) PAF activities, and platelet-rich plasma Delta CD62P activity (the mean fluorescent density difference between CD62P phycoerythrin-positive and -negative stains) were evaluated. Results: In the thrombotic group, plasma PAF (P=0.001), basal leukocyte PAF (P=0.017), induced leukocyte PAF (P=0.024), and Delta CD62P (P=0.023) levels were significantly higher than in the nonthrombotic group. In the whole group of Behcet's patients, there was a positive correlation between plasma PAF and Delta CD62P levels (r=0.533, P=0.002). When we compared clinically active and inactive patients with respect to the above parameters, there was no significant difference, irrespective of thrombosis. Plasma PAF (P=0.001), basal leukocyte PAF (P=0.004), and Delta CD62P (P=0.038) levels were significantly higher in the presence of both clinical activity and thrombosis than of clinical activity alone. Conclusion: Platelet-activating factor and CD62P may contribute to endothelial injury and thrombosis development in Behcet's disease. These two parameters seem related to the presence of thrombosis rather than clinical activity.C1 Suleyman Demirel Univ, Dept Rheumatol, Sch Med, Isparta, Turkey.Ege Univ, Sch Med, Dept Rheumatol, Izmir, Turkey.Celal Bayar Univ, Sch Med, Dept Rheumatol, Manisa, Turkey.Pamukkale Univ, Sch Med, Dept Rheumatol, Denizli, Turkey.Akdeniz Univ, Sch Med, Dept Immunorehumatol, Antalya, Turkey.Ege Univ, Sch Med, Dept Pediat & Membranol, Izmir, Turkey

Characteristics Predicting Tuberculosis Risk under Tumor Necrosis Factor-alpha Inhibitors: Report from a Large Multicenter Cohort with High Background Prevalence

WOS: 000378167600010PubMed ID: 26773107Objective. Screening strategies for latent tuberculosis (TB) before starting tumor necrosis factor (TNF)-alpha inhibitors have decreased the prevalence of TB among patients who are treated with these agents. However, despite vigilant screening, TB continues to be an important problem, especially in parts of the world with a high background TB prevalence. The aim of this study was to determine the factors related to TB among a large multicenter cohort of patients who were treated with anti-TNF. Methods. Fifteen rheumatology centers participated in this study. Among the 10,434 patients who were treated with anti-TNF between September 2002 and September 2012, 73 (0.69%) had developed TB. We described the demographic features and disease characteristics of these 73 patients and compared them to 7695 patients who were treated with anti-TNF, did not develop TB, and had complete data available. Results. Among the 73 patients diagnosed with TB (39 men, 34 women, mean age 43.6 +/- 13 yrs), the most frequent diagnoses were ankylosing spondylitis (n = 38) and rheumatoid arthritis (n = 25). More than half of the patients had extrapulmonary TB (39/73, 53%). Six patients died (8.2%). In the logistic regression model, types of anti-TNF drugs [infliximab (IFX), OR 3.4, 95% CI 1.88-6.10, p = 0.001] and insufficient and irregular isoniazid use (<9 mos; OR 3.15, 95% CI 1.43-6.9, p = 0.004) were independent predictors of TB development. Conclusion. Our results suggest that TB is an important complication of anti-TNF therapies in Turkey. TB chemoprophylaxis less than 9 months and the use of IFX therapy were independent risk factors for TB development