Anti-C1q Antibodies in Juvenile-Onset Systemic Lupus Erythematosus

The objective of this study was to evaluate the presence of anti-C1q antibodies Hospital Israelita Albert Einstein Research Institute, Sao Paulo, Brazil in 67 juvenile Systemic lupus erythematosus (JSLE) patients and 26 healthy controls and to assess the association of these antibodies with disease activity, nephritis, and presence of anti-double-stranded (ds)DNA. Anti-C1q antibodies were detected by ELISA. A higher frequency of anti-C1q antibodies was observed in JSLE patients compared to controls (20% vs. 0%, P = 0.016). Specificity of these antibodies was 100% [95% confidence interval (CI) 86.7-100%] and sensitivity was 19.4% (95% CI 10.7-30.8%) for a lupus diagnosis. The median anti-C1q antibodies was higher in JSLE patients compared to controls [median (range) 9.4 (5.5-127) vs. 7.3 (5-20) units, P = 0.004]. Remarkably, a positive Spearman`s coefficient was found between anti-dsDNA and anti-C1q units (r = 0.42, P = 0.0004, 95% CI 0.19-0.60). Our results confirm a low frequency of anti-C1q antibody in our lupus populations, but the presence of anti-C1q antibodies appears to be a good marker for JSLE diagnosis.

The spectrum of autoantibodies in IPEX syndrome is broad and includes anti-mitochondrial autoantibodies

IPEX syndrome is a congenital disorder of immune regulation caused by mutations in the FOXP3 gene, which is required for the suppressive function of naturally arising CD4 + CD25 + regulatory T cells. In this case series we evaluated serum samples from 12 patients with IPEX syndrome for the presence of common autoantibodies associated with a broad range of autoimmune disorders. We note that 75% of patients (9/12) had 1 or more autoantibodies, an incidence far above the cumulative rate observed in the general population. The range of autoantibodies differed between patients and there was no predominant autoantibody or pattern of autoantibodies present in this cohort. Surprisingly, one patient had high-titer anti-mitochondrial antibodies (AMA) typically associated with primary biliary cirrhosis (PBC) although the patient had no signs of cholestasis. PBC is a well-characterized autoimmune disease that occurs primarily in women and includes the serological hallmarks of serum AMA and elevated IgM which were both present in this patient. PBC is virtually absent in children with the exception of one reported child with interleukin 2 receptor a (CD25) deficiency which is associated with an IPEX-like regulatory T cell dysfunction. Based on the present data and the available literature we suggest a direct role for CD4 + CD25 + regulatory T cells in restraining B cell autoantibody production and that defects in regulatory T cells may be crucial to the development of PBC. (C) 2010 Elsevier Ltd. All rights reserved.

Decision-Making Deficits Linked to Real-life Social Dysfunction in Crack Cocaine-Dependent Individuals

Crack cocaine-dependent individuals (CCDI) present abnormalities in both social adjustment and decision making, but few studies have examined this association. This study investigated cognitive and social performance of 30 subjects (CCDI x controls); CCDI were abstinent for 2 weeks. We used the Social Adjustment Scale (SAS), Wisconsin Card Sorting Test (WCST), and Iowa Gambling Task (IGT). Disadvantageous choices on the IGT were associated with higher levels of social dysfunction in CCDI, suggesting the ecological validity of the IGT. Social dysfunction and decision making may be linked to the same underlying prefrontal dysfunction, but the nature of this association should be further investigated. (Am J Addict 2010;00: 1-9).

Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report

Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging. Regional cerebral blood flow (rCBF) at rest was measured twice using (99m)Tc-ECD SPECT in 10 treatment-naive patients with SAD. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping. Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001), reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (p < 0.001, uncorrected), and increased ECD uptake in the right posterior cingulate gyrus (p < 0.001, uncorrected). These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.

Social anxiety disorder: what are we losing with the current diagnostic criteria?

Objective: To assess the rate of comorbidities and the functional impairment associated with the social anxiety disorder (SAD), with an emphasis on the so-called subthreshold clinical signs and symptoms. Method: Psychiatric comorbidities and psychosocial functioning were evaluated in 355 volunteers (college students) who had been diagnosed as SAD (n = 141), Subthreshold SAD (n = 92) or Controls (n = 122). Results: The rate of comorbidities was 71.6% in the SAD group and 50% in subjects with Subthreshold SAD, both significantly greater than Controls (28.7%). Concerning psychosocial functioning, the SAD group had higher impairment than the other two groups in all domains evaluated, and subjects with Subthreshold SAD presented intermediate values. Conclusion: The rates of psychiatric comorbidities and the impairment of psychosocial functioning increase progressively along the spectrum of social anxiety. The fact that Subthreshold SAD causes considerable disability and suffering in comparison with control subjects justifies a review of the validity of the diagnostic criteria.

Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment

Anti-IgE, omalizumab, inhibits the allergen response in patients with asthma. This has not been directly related to changes in inflammatory conditions. We hypothesized that anti-IgE exerts its effects by reducing airway inflammation. To that end, the effect of anti-IgE on allergen-induced inflammation in bronchial biopsies in 25 patients with asthma was investigated in a randomized, double-blind, placebo-controlled study. Allergen challenge followed by a bronchoscopy at 24 h was performed at baseline and after 12 weeks of treatment with anti-IgE or placebo. Provocative concentration that causes a 20% fall in forced expiratory volume in 1 s (PC(20)) methacholine and induced sputum was performed at baseline, 8 and 12 weeks of treatment. Changes in the early and late responses to allergen, PC(20), inflammatory cells in biopsies and sputum were assessed. Both the early and late asthmatic responses were suppressed to 15.3% and 4.7% following anti-IgE treatment as compared with placebo (P < 0.002). This was paralleled by a decrease in eosinophil counts in sputum (4-0.5%) and postallergen biopsies (15-2 cells/0.1 mm(2)) (P < 0.03). Furthermore, biopsy IgE+ cells were significantly reduced between both the groups, whereas high-affinity IgE receptor and CD4+ cells were decreased within the anti-IgE group. There were no significant differences for PC(20) methacholine. The response to inhaled allergen in asthma is diminished by anti-IgE, which in bronchial mucosa is paralleled by a reduction in eosinophils and a decline in IgE-bearing cells postallergen without changing PC(20) methacholine. This suggests that the benefits of anti-IgE in asthma may be explained by a decrease in eosinophilic inflammation and IgE-bearing cells.

Activated status of basophils in chronic urticaria leads to interleukin-3 hyper-responsiveness and enhancement of histamine release induced by anti-IgE stimulus

Background Basophils and mast cells are the main target cells in chronic idiopathic urticaria (CIU). Besides the basopenia, intrinsic defects of the anti-IgE cross-linking signalling pathway of basophils have been described in CIU. Objectives We sought to investigate the profile of expression of activation markers on basophils of patients with CIU and to explore the effect of interleukin (IL)-3 priming upon anti-IgE cross-linking stimuli through expression of activation markers and basophil histamine releasability. Methods Evaluation of the surface expression of Fc epsilon RI alpha, CD63, CD203c and CD123 on whole blood basophils of patients with CIU undergoing autologous serum skin test (ASST) was performed by flow cytometry. The effect of pretreatment with IL-3 in the anti-IgE response was analysed by the expression of basophil activation markers and histamine release using enzyme-linked immunosorbent assay. Results Blood basophils of patients with CIU were reduced in number and displayed increased surface expression of Fc epsilon RI alpha, which was positively correlated with the IgE serum levels. Upregulation of expression of both surface markers CD203c and CD63 was verified on basophils of patients with CIU, regardless of ASST response. High expression of IL-3 receptor on basophils was detected only in ASST+ patients with CIU. Pretreatment with IL-3 upregulated CD203c expression concomitantly with the excreting function of blood basophils and induced a quick hyper-responsiveness to anti-IgE cross-linking on basophils of patients with CIU compared with healthy controls. Conclusions Basophils of patients with CIU showed an activated profile, possibly due to an in vivo priming. Functionally, basophils have high responsiveness to IL-3 stimulation, thereby suggesting that defects in the signal transduction pathway after IgE cross-linking stimuli are recoverable in subjects with chronic urticaria.

Evaluation of anti-inflammatory activity of derivatives from aerial parts of Baccharis uncinella

Context: Species of Baccharis exhibit antibiotic, antiseptic, and wound-healing properties, and have been used in the traditional medicine of South America for the treatment of inflammation, headaches, diabetes, and hepatobiliary disorders. Objective: To investigate the anti-inflammatory activity of organic phases from EtOH extract of the aerial parts of Baccharis uncinella DC (Asteraceae). Materials and methods: The crude EtOH extract from the aerial parts of B. uncinella was subjected to partition procedures and the corresponding CH(2)Cl(2) and EtOAc phases were subjected to several chromatographic separation procedures. Thus, these phases and their purified compounds were assayed for evaluation of anti-inflammatory activity. Results: The CH(2)Cl(2) phase from EtOH extract from B. uncinella contained two triterpenoids (oleanolic and ursolic acids) and one flavonoid (pectolinaringenin), whereas the respective EtOAc phase showed to be composed mainly by two phenylpropanoid derivatives (caffeic and ferulic acids). The CH(2)Cl(2) and EtOAc phases as well as their isolated compounds exhibited anti-inflammatory effects against inflammatory reactions induced by phospholipase A2 (from Crotalus durissus terrificus venom) and by carrageenan. Discussion and conclusion: The results suggested that the components obtained from partition phases of EtOH extract of B. uncinella could represent lead molecules for the development of anti-inflammatory agents. Additionally, the results confirmed the use of Baccharis genus in the traditional medicine of South America for the treatment of inflammation and other heath disorders. To date, the present work describes for the first time the anti-inflammatory effects of compounds isolated from B. uncinella.

Mucosal and systemic anti-GAG immunity induced by neonatal immunization with HIV LAMP/gag DNA vaccine in mice

Vaccines capable of inducing mucosal immunity in early postnatal life until adulthood, protecting early sexual initiation, should be considered as strategies to vaccination against HIV. The HIV-1 GAG protein as a chimera with the lysosome-associated membrane protein (LAMP/gag), encoded by a DNA vaccine, is targeted to the endosomal/lysosomal compartment that contains class II MHC molecules and has been shown to be immunogenic in adult mice. Assuming that one such strategy could help to overcome the immunological immaturity in the early postnatal period, we have evaluated the systemic and mucosal immunogenicity of LAMP/gag immunization in neonatal mice. Intranasal immunization with LAMP/gag vaccine induced higher levels of sIgA and IgG anti-GAG antibodies in intestinal washes than did the gag vaccine. The combination of ID injections and the IN protocol with the chimeric vaccine promoted the increase of Ab levels in sera. Both vaccines induced splenic IFN-gamma- secreting cells against GAG peptide pools, as well as in vivo cytotoxic T lymphocyte (CTL) function, and increased the percentage of CD8+ T cells to the immunodominant class I peptide in gut and spleen. However, only the chimeric vaccine was able to enhance Th1/Th2 cytokine secretion in response to class II GAG peptide and to enhance IL-4-secreting cells against GAG peptides and p24 protein stimuli. Long-lasting humoral and cellular responses were detected until adult age, following neonatal immunization with the chimeric vaccine. The LAMP/gag vaccination was able to induce potent GAG-specific T and B cell immune responses in early life which are essential to elicit sustained and long-lasting mucosal and systemic humoral response. (C) 2010 Elsevier GmbH. All rights reserved.

Airway epithelium mediates the anti-inflammatory effects of exercise on asthma

Airway epithelium plays an important role in the asthma physiopathology. Aerobic exercise decreases Th2 response in murine models of allergic asthma, but its effects on the structure and activation of airway epithelium in asthma are unknown. BALB/c mice were divided into control, aerobic exercise, ovalbumin-sensitized and ovalbumin-sensitized plus aerobic exercise groups. Ovalbumin sensitization occurred on days 0, 14, 28, 42, and aerosol challenge from day 21 to day 50. Aerobic exercise started on day 22 and ended on day 50. Total cells and eosinophils were reduced in ovalbumin-sensitized group submitted to aerobic exercise. Aerobic exercise also reduced the oxidative and nitrosative stress and the epithelial expression of Th2 cytokines, chemokines, adhesion molecules, growth factors and NF-kB and P2X7 receptor. Additionally, aerobic exercise increased the epithelial expression of IL-10 in non-sensitized and sensitized animals. These findings contribute to the understanding of the beneficial effects of aerobic exercise for chronic allergic airway inflammation, suggesting an immune-regulatory role of exercise on airway epithelium. (C) 2011 Elsevier B.V. All rights reserved.