The traditional concept that effector T helper (Th) responses are mediated by Th1/Th2 cell subtypes has been broadened by the recent demonstration of two new effector T helper cells, the IL-17 producing cells (Th17) and the follicular helper T cells (Tfh). These new subsets have many features in common, such as the ability to produce IL-21 and to express the IL-23 receptor (IL23R), the inducible co-stimulatory molecule ICOS, and the transcription factor c-Maf, all of them essential for expansion and establishment of the final pool of both subsets. Tfh cells differ from Th17 by their ability to home to B cell areas in secondary lymphoid tissue through interactions mediated by the chemokine receptor CXCR5 and its ligand CXCL13. These CXCR5+ CD4+ T cells are considered an effector T cell type specialized in B cell help, with a transcriptional profile distinct from Th1 and Th2 cells. The role of Tfh cells and its primary product, IL-21, on B-cell activation and differentiation is essential for humoral immunity against infectious agents. However, when deregulated, Tfh cells could represent an important mechanism contributing to exacerbated humoral response and autoantibody production in autoimmune diseases. This review highlights the importance of Tfh cells by focusing on their biology and differentiation processes in the context of normal immune response to infectious microorganisms and their role in the pathogenesis of autoimmune diseases.
The aim of this study was to evaluate traditional risk factors for coronary artery disease (CAD), homocysteine, anti-oxidized low-density lipoprotein (anti-oxLDL), anti-lipoprotein lipase (anti-LPL) and endothelin-1 (ET-1) in patients with primary anti-phospholipid syndrome (APS), furthermore verify possible association among these variables and arterial thrombosis. Thirty-eight women with primary APS and 30 age-and-sex-matched controls were evaluated. Patients presented higher-LDL and triglycerides levels and lower-HDL levels than controls. Anti-LPL antibodies were not detected in both groups. The mean number of risk factors was higher in patients than in controls (P = 0.030). Anti-oxLDL antibodies, homocysteine and ET-1 mean levels were similar between groups, but abnormal homocysteine levels were found only among primary APS patients (P = 0.031). Hypertension and the presence of at least one risk factor for CAD were more prevalent in patients with arterial involvement than those without. Homocysteine levels and mean number of risk factors for CAD were significantly higher in patients with arterial thrombosis than controls. In a multivariate analysis hypertension was the only independently associated with arterial thrombosis (OR 14.8, 95% CI = 2.1-100.0, P = 0.006). This study showed that in primary APS patients other risk factors besides anti-phospholipid antibodies contribute for the occurrence of arterial events and the most important factor was hypertension.
The objective of the present research was to evaluate the usefulness of anti-cyclic citrullinated peptide (anti-CCP) antibodies and the IgM rheumatoid factor (IgM RF) test for the differential diagnosis of leprosy with articular involvement and rheumatoid arthritis (RA). Anti-CCP antibodies and IgM RF were measured in the sera of 158 leprosy patients (76 with and 82 without articular involvement), 69 RA patients and 89 healthy controls. Leprosy diagnosis was performed according to Ridley and Jopling classification criteria and clinical and demographic characteristics of leprosy patients were collected by a standard questionnaire. Leprosy patients with any concomitant rheumatic disease were excluded. Serum samples were obtained from all participants and frozen at -20°C. Measurement of anti-CCP antibodies and IgM RF were performed by ELISA, using a commercial second-generation kit, and the latex agglutination test, respectively. Anti-CCP antibodies and IgM RF were detected in low frequencies (2.6 and 1.3%, respectively) in leprosy patients and were not associated with articular involvement. Among healthy individuals both anti-CCP antibodies and IgM RF were each detected in 3.4% of the subjects. In contrast, in the RA group, anti-CCP antibodies were present in 81.2% and IgM RF in 62.3%. In the present study, both anti-CCP antibodies and IgM RF showed good positive predictive value for RA, helping to discriminate between RA and leprosy patients with articular involvement. However, anti-CCP antibodies were more specific for RA diagnosis in the population under study.
Background The literature shows that acute exercise increases IL-6 [1,2] and IL-10 [3,4] and TNF-a [5,6] serum levels in healthy subjects and can worse the inflammatory response in patients with diabetes mellitus type I, cystic fibrosis and obstructive pulmonary disease [7]. Some studies showed resting SLE patients have higher levels of IL-6 [8,9] and IL-10 [8,10] compared to healthy controls. Although being established in the literature that SLE patients have benefits with the aerobic training [11] mainly related to cardiovascular risk factors, there is no study evaluating the effect of acute exercise on the cytokines levels in SLE patients what could cause some concerning about the risk of worsening inflammatory cytokines Objectives To assess the levels of IL-10, IL-6 and TNF-a at baseline and after acute exercise in SLE patients Methods Thirty female SLE patients (≥4 ACR criteria) with inactive or mild disease activity, and 30 age-and gender-matched healthy controls were included. At baseline and soon after the ergospirometric test 10 ml of peripheral blood were collected for IL-10, IL-6 and TNF-a measurement by ELISA technique (R&D Systems, Inc.-Minneapolis, USA). The disease activity was evaluated by SLEDAI. The Student’s t-tests and Mann-Whitney test were used for intra and inter-group comparisons. P values <0.05 were considered significant. All participants signed Institutional Ethic Committee approved consent form. Results The mean age of patients and controls were comparable (32.58±7.44 y.o vs 30.43±7.76 y.o, p=0,275). The mean disease duration was 105.5±85.55 months and the mean SLEDAI score was 1.96±2.32. SLE patients presented worst ergospirometric parameters compared to controls: VO2máx (ml/kg/min) (25.27±5.20 vs 32.74±5.85, P<0.001); VO2max (l/min) (1.61±0.36 vs 1.98±0.36 P<0.001); maximum heart rate (174.75±2.34 vs 185.15±2.07 P=0.002); maximum ventilation (VEmax) (66.33±15.68 vs 80.48±18.98, P=0.001) and maximum speed (Km/h) (7.68±1.24 vs 9.4±1.22 P<0.001). At baseline SLE patients presented higher levels of IL-6 [2.85±2,68 vs 1.58±1.62 p=0.005] and IL-10 [1.00±2.1 vs -0.44±1.20 p=0.002] comparing to controls. The acute exercise did not significantly alter the levels of IL-6, IL-10 and TNF-a in SLE patients. On the other hand, in the control group, the acute exercise increased IL-6 level [1.8±1.62 vs 1.91±1.52; p=0.001] without significant change on IL-10 and TNF-α levels. Conclusions IL-6 and IL-10 levels were higher in SLE patients than in controls. Acute physical exercise increased IL-6 levels in healthy women, but, in SLE patients did not significantly changed the levels of IL-6, IL-10 or TNF-a. We concluded does not appear that acute exercise increase inflammatory cytokines and disease exacerbation in SLE patients with inactive or mild disease activity. References Nieman et al. Med. Sci. Sports Exerc., 2005. Pedersen. J Exp Biol. 2011. Yakeu et al. Atherosclerosis. 2010. Paalani et al. Ethn Dis 2011. Sandri et al. Eur J Cardiovasc Prev Rehabil. 2011. Hallberg et al. J Affect Disord. 2010...
Background Cardiovascular disease (CVD) is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE) and disturbances in endothelial function (EF) are implicated in its pathogenesis (1,2). EF also depends on endothelial progenitor cells (EPCs) that enhance angiogenesis, promote vascular repair and have potential as a marker of CVD (3,4,5). SLE patients have endothelial dysfunction and fewer EPCs (6,7). Objectives To evaluate the effect of supervised physical exercise (SPE) on quality of life, exercise tolerance, body composition, endothelial function, EPCs number and on vascular endothelial growth factor (VEGF) level in SLE patients. Methods Prospective, controlled, nonrandomized study. Women with SLE were allocated according to availability to participate in exercise group (EG) or control group (CG). Intervention: SPE was performed for 1 hour, 3X/week, for 16 weeks. Patients were evaluated at baseline (T0) and after 16 weeks (T16): exercise tolerance by cardiopulmonary exercise test; quality of life by SF-36; body composition by DEXA; high-resolution ultrasound of brachial artery in resting conditions, after reactive hyperaemia (flow-mediated dilation-FMD) and after oral glyceryl trinitrate (GTMD) was performed to assess endothelial function; EPCs were evaluated by flow cytometry using anti-CD34 (FITC), anti-CD133 (PE) and anti-KDR (APC); and VEGF was assessed by ELISA (R&D Systems, Minneapolis, USA). Results 535 SLE patients were invited, 239 manifested interest, but 127 were excluded due to exclusion criteria. 55 patients dropped out due to personal reasons. Twenty four patients completed the evaluations (mean age 33.2±8.2 years and mean disease duration of 99±77.9 months). Thirteen patients were assigned in the EG and eleven in the CG. Both groups were comparable and homogeneous regarding demographic variables and cardiovascular traditional risk factors. After 16 weeks, we observed a significant increase in FMD (7.7±7.2% vs 16.9±8.8%, p=0.005) in EG without changes in the GC (4.1±4.4% vs 7.4±5.7%, p=0.62). In the EG, we also found a significant improvement in exercise tolerance (12±2.1min vs 13.5±2min, p=0.021), maximum speed (7.6±1km/h vs 8.3±1km/h, p=0.049), threshold speed (5.5±0.6km/h vs 5.9±0.6km/h, p=0.012), functional capacity (66.2±23.8 vs 82.1±11.6, p=0.035) and vitality (72.9±31.4 vs 78.8±19.7, p=0.007). EPCs were analyzed in 10 patients of the EG and in seven of the CG. We observed a significant increase in number of CD34/CD133/KDR positive cells at T16 in the EG (0.38±0.37 vs. 1.57±1.38, p=0.005), with no difference in the CG (0.62±0.83 vs. 0.82±0.58, p=0.176). There was no difference on body composition and VEGF levels in both groups comparing T0 and T16. Conclusions Despite the small sample, this is the first study demonstrating that SPE can improve EF and EPCs number in SLE patients. The higher number of EPCs may be one of the mechanisms associated with EF improvement after an exercise program. Physical exercise can be a useful strategy to prevent CVD morbidity and ...
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