Publications (3)13.47 Total impact
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Article: Effect of fluoride exposure on different immune parameters in humans.
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ABSTRACT: T regulatory (Treg) cells play an important role in the modulation of the immune response, and are implicated in the pathogenesis of autoimmune diseases. Many people is exposed to fluoride (F), mainly through drinking water. The aim of this work was to assess the possible effect of F exposure on different immune parameters, mainly Treg cells. We studied 61 subjects from a community of the state of Durango, Mexico, where the population is exposed to F levels over 2.0 ppm in drinking water. Peripheral blood mononuclear cells (PBMC) were isolated and the level and function of Treg cells was analyzed by flow cytometry and cell proliferation assays. In addition, we detected the presence of apoptotic cells, the expression of TLR/CD14, and the in vitro synthesis of TNF-α by monocytes. We found a negative correlation between urinary F and percentage of CD4(+)CD25(+) Treg cells (r = -0.55, P < 0.001). Accordingly, a defective function of these cells was detected in 30% of individuals exposed to F. In contrast, a positive association between levels of CD4(+)TGF-β(+) or CD4(+)IL-10(+) Treg lymphocytes and F urine concentrations was detected. In addition, a negative correlation was detected between the F urinary levels and the proportion of apoptotic cells, in PBMC or T cells or monocytes (P < 0.05 in all cases). Finally, no apparent association between F exposure and TLR4/CD14 expression or the synthesis of TNF-α was detected. Our data suggest that F exposure exerts a complex and relevant effect on Treg cells in humans.Immunopharmacology and Immunotoxicology 03/2011; 33(1):169-77. · 1.83 Impact Factor -
Article: Regulatory T cells in patients with systemic lupus erythematosus.
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ABSTRACT: Regulatory T cells have an important role in the control of self-reactivity, and in the pathogenesis of autoimmune inflammatory conditions. The aim of this work was to perform a quantitative and functional analysis of regulatory T cells in patients with systemic lupus erythematosus (SLE). We studied twenty-three patients with SLE (19 active, 4 inactive), and twenty-seven healthy subjects as well as fifteen patients with rheumatoid arthritis (RA). The following cell subsets were analyzed in peripheral blood mononuclear cells by flow cytometry: CD4+CD25+, CD4+CD25(bright), CD4+Foxp3+ (Treg cells), CD8+CD28- (Ts cells), CD4+IL-10+ (Tr1 cells), and CD4+TGF-beta+ (Th3 cells). In addition, the in vitro suppressive activity of CD4+CD25+ lymphocytes was tested. We found no significant differences in the levels of all regulatory cell subsets studied in SLE patients compared to controls and RA patients. However, a defective regulatory function of CD4+CD25+T cells was observed in a significant fraction (31%) of patients with SLE. Our data indicate that although approximately one third of patients with SLE show an abnormal immunosuppressive function of Treg lymphocytes, their levels of the different regulatory T cell subsets in peripheral blood are not significantly different from those found in controls.Journal of Autoimmunity 10/2006; 27(2):110-8. · 7.37 Impact Factor -
Article: Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study.
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ABSTRACT: We studied the clinical and immunological effects of Rituximab (anti-CD20) therapy in patients with lupus nephritis. In an open clinical trial, 22 patients with active systemic lupus erythematosis and renal involvement (mainly class III and IV according to the WHO classification) that was refractory to conventional therapy were studied. In all these patients, Rituximab (0.5 to 1.0 g at days 1 and 15) was added to the immunosuppressive therapy and its therapeutic effect was evaluated. In addition, the levels and function of regulatory T lymphocytes and the apoptosis of immune cells were assessed. We found a significant reduction in disease activity (p < 0.05, MEX-SLEDAI index), and proteinuria (p < 0.05) at days 60 and 90 of Rituximab therapy. Although most patients showed improvement in creatinine clearance and erythrocyturia, no significant changes in these parameters were detected. In most patients (20/22), B cell depletion was observed, but no clear-cut effect of Rituximab on complement levels or auto-antibody titers was detected (p > 0.05 in all cases). One patient died at day 70 with invasive histoplasmosis. No important adverse effects of Rituximab therapy were registered in other patients. A significant enhancement in the levels of different CD4+ regulatory cells (TREG, Th3, Tr1), but not CD8+ Ts lymphocytes, was observed at day 30. This increase was sustained for TREG cells at day 90, and accompanied by an improvement in their regulatory function. In addition, we observed an unexpected increase in the apoptosis of T cells at day 30. Interestingly, the enhancement in the suppressive function of TREG cells was not observed in the two patients that showed the poorest clinical response to Rituximab. We conclude that the data obtained in this open clinical trial suggest that Rituximab is a promising candidate for randomized controlled trials in patients with lupus nephritis refractory to the conventional immunosuppressive therapy. The effects of Rituximab on regulatory cells and apoptosis of T lymphocytes are interesting and its possible role in the putative effect of this biological agent in systemic lupus erythematosis deserves additional studies.Arthritis research & therapy 01/2006; 8(3):R83. · 4.27 Impact Factor
