Genetic variation of FcγRIIa induces higher uptake of Leishmania infantum and modulates cytokine production by adherent mononuclear cells in vitro.

Introduction: Single nucleotide variations (SNVs) are specific genetic variations that commonly occur in a population and often do not manifest phenotypically. However, depending on their location and the type of nucleotide exchanged, an SNV can alter or inhibit the function of the gene in which it occurs. Immunoglobulin G (IgG) receptor genes have exhibited several polymorphisms, including rs1801274, which is found in the FcgRIIa gene. The replacement of A with T results in a Histidine (H) to Arginine (R) substitution, altering the affinity of the IgG receptor for IgG subtypes and C-reactive protein (CRP). In this study, we analyzed rs1801274 and its functional implications concerning L. Infantum uptake and cytokine production. Methods: We genotyped 201 individuals from an endemic area for visceral leishmaniasis to assess the presence of rs1801274 using Taqman probes for a candidate gene study. Additionally, we included seventy individuals from a non-endemic area for a functional study. Subsequently, we isolated and cultivated one-week adherent mononuclear cells (AMCs) derived from the peripheral blood of participants residing in the non-endemic region in the presence of L. infantum promastigotes, with and without antigen-specific IgG and/or CRP. We analyzed the rate of phagocytosis and the production of nitric oxide (NO), tumor necrosis factor (TNF)-a, interleukin (IL)-10, IL-12 p70, IL-1b, IL- 6, and IL-8 in the culture supernatants. Results and discussion: In participants from the endemic region, the A/G (H/R isoform) heterozygous genotype was significantly associated with susceptibility to the disease. Furthermore, SNVs induced a change in the phagocytosis rate in an opsonin-dependent manner. Opsonization with IgG increased the production of IL-10, TNF-a, and IL-6 in AMCs with the H/R isoform, followed by a decrease in NO production. The results presented here suggest that the rs1801274 polymorphism is linked to a higher susceptibility to visceral leishmaniasis.

IgG Subclass Analysis in Patients with Chagas Disease 4 Years After Benznidazole Treatment.

BACKGROUND: In humans, Trypanosoma cruzi infection is controlled by a complex immune response. Immunoglobulin G (IgG) is important for opsonizing blood trypomastigotes, activating the classic complement pathway, and reducing parasitemia. The trypanocidal activity of benznidazole is recognized, but its effects on the prevention and progression of Chagas disease is not well understood OBJECTIVE: We aimed to evaluate the levels of total IgG and cross-specific IgG subclasses in patients with chronic Chagas disease of different clinical forms before and after 4 years of benznidazole treatment. METHODS: Eight individuals with the indeterminate form and nine with the cardiac form who completed the treatment protocol were evaluated. The levels of total IgG and IgG1, IgG2, IgG3, and IgG4 isotypes were quantified in the serum of each individual using the fluorescent immunosorbent assay. The results are expressed as relative fluorescence unit. RESULTS: Patients with chronic Chagas disease presented decreased levels of total IgG at 48 months after benznidazole treatment. Increased IgG1 and decreased IgG3 levels were observed in patients with the cardiac form and those with exacerbated clinical forms. In addition, a decrease in the IgG3/IgG1 ratio was observed in individuals with the cardiac form of Chagas disease. CONCLUSIONS: Benznidazole administration in the chronic phase differentially changes IgG subclasses in patients with cardiac and indeterminate forms, and monitoring the IgG3 level may indicate the possible prognosis to the cardiac form or worsening of the already established clinical form.

Effects of the laying on of hands on anxiety, stress and autonomic response of employees in a hospital: A double-blind randomized controlled trial.

Mental and behavioral disorders result in increased absenteeism and abandonment of work. The objective of this study was to evaluate the anxiety, stress, depression, negative and positive affects, and hematological and autonomic responses of employees in a public hospital exposed to laying on of hands with (LHS) or without Spiritual connection (control-LHW). METHODOLOGY: Eighty-four employees with anxiety/stress were enrolled and randomly allocated into two groups of intervention LHS by Spiritist "passe" and control-LHW by volunteers with healing intent. Anxiety, stress and depression were evaluated by Depression Anxiety and Stress Scale (DASS21). Negative and positive affects by Subjective Well-being Scale (SWS), cardiac autonomic modulation by heart rate variability and cytokines and blood count were assessed by blood sample. RESULTS: Our study showed a significant improvement in the neutrophils (p = 0.041; d = 0.70) and cardiac parasympathetic activity, and reduction in VLF (p < 0.005) in the LHS. There was reduction in erythrocyte parameters and interleukin 10 (p < 0.005) in the control-LHW. In both groups there was a significant reduction in anxiety, stress, depression and negative affects after one session (p < 0.005). CONCLUSION: Laying on of hands with Spiritual connection by Spiritist "passe" appears to be effective in increasing cardiac vagal activity and regulation of immune responses of employees in a public hospital with stress/anxiety.

Pemphigus foliaceus patients (Fogo Selvagem) treated with kinesiotherapy presented lower levels of proinflammatory cytokines.

Fogo Selvagem (FS) is a rare autoimmune disease characterized by acantholysis and inflammation of the epidermis. It was evidenced in this disease the increase of proinflammatory cytokines levels which can be influenced by physical activities. Kinesiotherapy, as physiotherapeutic interventions, was associated improvement levels of the quality of live, mainly the pain. Understanding the impact of such methodology in immunology of the FS, may constitute an alternative and effective approach. We compare the levels of serum cytokines and chemokines between nine patients with FS submitted to kinesiotherapy for 12 weeks and ten patients not submitted to kinesiotherapy. The kinesiotherapy was composed by self-stretching followed by a resistance training for upper and lower limbs. The protocol was carried out in three sections of eight to ten repetitions with 70% of the maximum load measured by test maximum of ten repetitions. After strengthening period patients performed a passive stretching. The training sessions lasted 50 min and were performed 3 times a week at least 12 weeks. Cytokines and chemokines were assessed in plasma using enzyme-linked immunosorbent assay and/or cytometric bead array. Patients with FS were being kinesiotherapy presented minors levels of interferon-γ, interleukin (IL)-17, IL-22, and IL-15 when compared to those not submitted to kinesiotherapy. No differences were observed for the detection of the chemokines chemokine ligand (CCL)-2, CCL-3, CCL-5, CCL-11, C-X-C motif chemokine 8 (CXCL-8), and CXCL-10. These results suggest that kinesiotherapy had a positive impact on inflammatory markers that are associated with disease worsening in FS.

T-Cell Immunophenotyping and Cytokine Production Analysis in Patients with Chagas Disease 4 Years after Benznidazole Treatment.

The major problem with Chagas disease is evolution of the chronic indeterminate form to a progressive cardiac disease. Treatment diminishes parasitemia but not clinical progression, and the immunological features involved are unclear. Here, we studied the clinical course and the immune response in patients with chronic-phase Chagas disease at 48 months after benznidazole treatment. Progression to the cardiac form of Chagas disease or its aggravation was associated with higher in vitro antigen-specific production of interferon gamma (IFN-γ) in patients with cardiac Chagas disease than in patients with the indeterminate form. Predominance of IFN-γ production over interleukin-10 (IL-10) production in antigen-specific cultures was associated with cardiac involvement. Significantly higher numbers of antigen-specific T helper 1 cells (T-Bet+ IFN-γ+) and a significantly higher IFN-γ+/IL-10+ ratio were observed in patients with cardiac Chagas disease than in patients with the indeterminate form. Cardiac damage was associated with higher numbers of T helper cells than cytotoxic T lymphocytes producing IFN-γ. Patients with cardiac Chagas disease had predominant CD25- and CD25low T regulatory (Treg) subpopulations, whereas patients with the indeterminate form manifested a higher relative mean percentage of CD25high Treg subpopulations. These findings suggest that at 48 months after benznidazole treatment, the disease can worsen or progress to the cardiac form. The progression may be related to increased IFN-γ production (mostly from CD4+ T cells) relative to IL-10 production and increased Treg percentages. Patients with the indeterminate form of Chagas disease show a more balanced ratio of proinflammatory and anti-inflammatory cytokines.

Cytokine and Chemokines Alterations in the Endemic Form of Pemphigus Foliaceus (Fogo Selvagem).

INTRODUCTION: The endemic form (fogo selvagem-FS) of pemphigus foliaceus is an autoimmune disease characterized by the presence of IgG autoantibodies against desmoglein-1. Despite the array of findings, the role of chemokines and cytokines that dictate the immune response and disease outcome is still poorly investigated. MATERIALS AND METHODS: Serum from 64 patients diagnosed with FS was used to draw and establish the levels of these molecules on this disease and establish the levels of these molecules with the severity of FS, and influence of treatment. RESULTS: In comparison to healthy subjects, FS patients, newly diagnosed and still without therapeutic intervention, had higher levels of IL-22 and CXCL-8, and reduced levels of IFN-γ, IL-2, IL-15, and CCL-11. Furthermore, treatment using immunosuppressant drugs augmented the production of IFN-γ, IL-2, CCL-5, and CCL-11 besides reducing the levels of IL-22 and CXCL-10. Immunosuppressive therapy seemed to have long-lasting effects on the production of higher amounts of IFN-γ, IL-2, and CCL-5, besides keeping lowered the levels of IL-22 in remission FS patients. CONCLUSION: Taken together, our findings suggest a putative role of IL-22 in the pathogenesis of FS. Finally, data presented here may contribute for better understanding the immune aspects that control disease outcome.