Expansion of CD4+CD25+and FOXP3+ regulatory T cells during the follicular phase of the menstrual cycle: implications in human reproduction

Regulatory T cells (Tregs) are thought to affect the severity of various infectious and autoimmune diseases. The incidence of autoimmune disease is higher in fertile women than in men. Thus, we investigated whether Treg numbers were modulated during the menstrual cycle by sex hormones. In fertile nonpregnant women, we detected an expansion of CD4 CD25 FOXP3 Tregs in the late follicular phase of the menstrual cycle. This increase was tightly correlated with serum levels of estradiol and was followed by a dramatic decrease in Treg numbers at the luteal phase. Women who have had recurrent spontaneous abortions (RSA) showed similarly low numbers of Tregs at both the follicular and luteal phases, comparable to numbers we observed in postmenopausal women. In addition to decreased numbers, Tregs from women with RSA were also functionally deficient, as higher numbers were required to exert a similar magnitude of suppression to CD4 CD25 FOXP3 cells from fertile women. Consequently, reproductive failure might result from the inability of Tregs in women with RSA to expand during the preimplantatory phase combined with their lower functional capacity. Additionally, the modulation of Treg numbers we observed in fertile women suggests that the stage of the menstrual cycle should be taken into account when Treg numbers are investigated clinically. The Journal of Immunology, 2007, 178: 2572–2578.Fil: Arruvito, Maria Lourdes. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sanz, Marianela. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Banham, Alison H.. University of Oxford; Reino UnidoFil: Fainboim, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentin

Hepatitis A, B and C viral co-infections among HIV-infected adults presenting for care and treatment at Muhimbili National Hospital in Dar es Salaam, Tanzania

<p>Abstract</p> <p>Background</p> <p>Tanzania is currently scaling-up access to anti-retro viral therapy (ART) to reach as many eligible persons as possible. Hepatitis viral co-infections are known to influence progression, management as well as outcome of HIV infection. However, information is scarce regarding the prevalence and predictors of viral hepatitis co-infection among HIV-infected individuals presenting at the HIV care and treatment clinics in the country.</p> <p>Methods</p> <p>A cross-sectional study conducted between April and September 2006 enrolled 260 HIV-1 infected, HAART naïve patients aged ≥18 years presenting at the HIV care and treatment clinic (CTC) of the Muhimbili National Hospital (MNH). The evaluation included clinical assessment and determination of CD4+ T-lymphocyte count, serum transaminases and serology for Hepatitis A, B and C markers by ELISA.</p> <p>Results</p> <p>The prevalence of anti HAV IgM, HBsAg, anti-HBc IgM and anti-HCV IgG antibodies were 3.1%, 17.3%, 2.3% and 18.1%, respectively. Dual co-infection with HBV and HCV occurred in 10 individuals (3.9%), while that of HAV and HBV was detected in two subjects (0.8%). None of the patients had all the three hepatitis viruses. Most patients (81.1%) with hepatitis co-infection neither had specific clinical features nor raised serum transaminases. History of blood transfusion and jaundice were independent predictors for HBsAg and anti-HBc IgM positivity, respectively.</p> <p>Conclusion</p> <p>There is high prevalence of markers for hepatitis B and C infections among HIV infected patients seeking care and treatment at MNH. Clinical features and a raise in serum alanine aminotransferase were of limited predictive values for the viral co-infections. Efforts to scale up HAART should also address co-infections with Hepatitis B and C viruses.</p

Liver infiltrating mononuclear cells in children with type 1 autoimmune hepatitis

OBJECTIVE: To investigate infiltrating cells in the liver of children with type 1 autoimmune hepatitis (AH‐1). METHODS: liver biopsies from 24 untreated AH‐1 patients (14 children, 10 adults), five patients with hepatitis C virus related chronic hepatitis (HCV), and 10 control liver specimens (CL) were processed for immunohistochemical cell characterisation. RESULTS: Two different cell distribution patterns were detected in the liver of patients with AH‐1: (1) CD4(+) and CD20(+) cells were found in the central areas of the portal tracts (portal distribution); (2) CD8(+) cells were observed at the periphery of the portal space (periportal distribution). Some cell subsets, like CD56, CD57, Fas‐L, and Bak, showed a non‐defined distribution pattern. The presence of two well defined patterns of cell distribution was not observed in HCV and CL (CD4(+), CD20(+), and CD8(+) cells were uniformly distributed in the portal space). In AH‐1 and CL, the NK markers CD56 and CD57 were found scattered throughout the liver parenchyma. However, in HCV biopsies, CD56(+) cells were also clearly increased in both the portal and the periportal areas. Biopsies of AH‐1 and HCV patients showed a uniform distribution of Fas‐L and Bak in the portal and periportal areas, with Bak staining also detected in the hepatic parenchyma. CONCLUSIONS: Despite clinical and genetic differences, there was a similar distribution of liver infiltrating mononuclear cells in children and adults with AH‐1. These results raise the possibility of reclassifying cryptogenic chronic hepatitis by immunohistochemical analysis of infiltrating liver cells

La proteína transportadora del factor de crecimiento insulínico Tipo 1: ¿un nuevo marcador para la enfermedad hepática grasa no alcohólica?

Objetivo: evaluar la presencia de enfermedad hepáticagrasa no alcohólica en pacientes con factores de riesgo para esta patología (obesidad, síndrome metabólico y diabetes tipo 2) y determinar el papel de la insulina, índice HOMA, IGFBP-1, SHBG y PAI-1, como marcadores bioquímicos. Métodos: se evaluaron 91 pacientes con factores de riesgo para desarrollar enfermedad hepática grasa no alcohólica. Se determinaron en plasma transaminasas, insulina, SHBG, IGFBP-1 y PAI-1. El diagnóstico de enfermedad hepática se efectuó por ecografía y a 31 individuos, los cuales tenían esteatosis por ecografía y alanina aminotransferasa elevada, y a quienes se les practicó biopsia hepática. Resultados: la enfermedad hepática estuvo presente en 65 de los 91 pacientes (71,4%). La biopsia hepática efectuada en 31 pacientes diagnosticó la esteatohepatitis no alcohólica en todos y 25 pacientes tuvieron diferentes grados de fibrosis. Aquellos individuos con hígado graso tenían mayor circunferencia de cintura, niveles séricos de triglicéridos, insulina e índice HOMA y niveles más bajos de IGFBP-1, comparada con aquellos sin esteatosis. El grado de esteatosis hepática por ecografía correlacionó positivamente con la circunferencia de cintura, triglicéridos, insulina e índice HOMA (p<0,003; p<0,003; p<0,002 y p<0,001, respectivamente) y negativamente con HDL-colesterol e IGFBP-1 (p<0,025 y p<0,018, respectivamente). Conclusiones: se encontró una alta prevalencia de la EHGNA en pacientes con factores de riesgo metabólico, la mayoría con sobrepeso u obesidad. La SHBG y el PAI-1, aunque están íntimamente relacionados con la insulinorresistencia, no mostraron ser un marcador bioquímico de EHGNA. Si bien la disminución del nivel de IGFBP- 1 correlacionó con EHGNA, su determinación no sólo es menos accesible que la insulina, los triglicéridos, el índice HOMA y la circunferencia de cintura, sino además, la IGFBP-1 no es mejor marcador que los anteriormente nombrados