RESUMEN
BACKGROUND: Fabry nephropathy is a consequence of the deposition of globotriaosylceramide, caused by deficient GLA enzyme activity in all types of kidney cells. These deposits are perceived as damage signals leading to activation of inflammation resulting in renal fibrosis. There are few studies related to immunophenotype characterization of the renal infiltrate in kidneys in patients with Fabry disease and its relationship to mechanisms of fibrosis. This work aims to quantify TGF-ß1 and active caspase 3 expression and to analyze the profile of cells in inflammatory infiltration in kidney biopsies from Fabry naïve-patients, and to investigate correlations with clinical parameters. METHODS: Renal biopsies from 15 treatment-naïve Fabry patients were included in this study. Immunostaining was performed to analyze active caspase 3, TGF-ß1, TNF-α, CD3, CD20, CD68 and CD163. Clinical data were retrospectively gathered at time of kidney biopsy. RESULTS: Our results suggest the production of TNFα and TGFß1 by tubular cells, in Fabry patients. Active caspase 3 staining revealed that tubular cells are in apoptosis, and apoptotic levels correlated with clinical signs of chronic kidney disease, proteinuria, and inversely with glomerular filtration rate. The cell infiltrates consisted of macrophages, T and B cells. CD163 macrophages were found in biopsy specimens and their number correlates with TGFß1 and active caspase 3 tubular expression. CONCLUSIONS: These results suggest that CD163+ cells could be relevant mediators of fibrosis in Fabry nephropathy, playing a role in the induction of TGFß1 and apoptotic cell death by tubular cells. These cells may represent a new player in the pathogenic mechanisms of Fabry nephropathy.
Asunto(s)
Antígenos de Diferenciación Mielomonocítica , Apoptosis , Caspasa 3 , Enfermedad de Fabry , Fibrosis , Factor de Crecimiento Transformador beta1 , Humanos , Enfermedad de Fabry/patología , Enfermedad de Fabry/complicaciones , Masculino , Adulto , Femenino , Persona de Mediana Edad , Antígenos de Diferenciación Mielomonocítica/metabolismo , Caspasa 3/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Biopsia , Antígenos CD/metabolismo , Riñón/patología , Riñón/inmunología , Estudios Retrospectivos , Factor de Necrosis Tumoral alfa/metabolismo , Macrófagos/patología , Receptores de Superficie Celular/metabolismo , Tasa de Filtración Glomerular , Adulto Joven , Enfermedades Renales/patología , Enfermedades Renales/etiología , Túbulos Renales/patología , Trihexosilceramidas/metabolismo , Linfocitos T/inmunologíaRESUMEN
The objective of this work was to test the protective effect of a mixture (MM) constituted by kefir-isolated microorganisms (Lactobacillus plantarum, Lactobacillus kefir, Lc. lactis, Kluyveromyces marxianus and Saccharomyces cerevisiae) in a hamster model of infection with Clostridium difficile, an anaerobic Gram-positive bacterium that causes diarrhoea. Placebo or MM was administered ad libitum in drinking water from day 0 to the end of treatment. Hamsters received orally 200 µg of clyndamicin at day 7 and then were infected with 1 × 10(8) CFU of C. difficile by gavage. Development of diarrhoea and death was registered until the end of the protocol. Surviving animals were sacrificed at day 16, and a test for biological activity of clostridial toxins and histological stainings were performed in caecum samples. Six of seven infected animals developed diarrhoea and 5/7 died at the end of the experimental protocol. The histological sections showed oedema and inflammatory infiltrates with neutrophils and crypt abscesses. In the group of animals infected and treated with MM1/1000, only 1 of 7 hamsters showed diarrhoea and none of them died. The histological sections showed only a slight thickening of the mucosa with presence of lymphocytic infiltrate. These results demonstrate that an oral treatment with a mixture of kefir-isolated bacteria and yeasts was able to prevent diarrhoea and enterocolitis triggered by C. difficile.