ABSTRACT
Abstract Objective: There is evidence of an important role of immune system changes in the triggering and maintenance of idiopathic nephrotic syndrome (INS). The aim of this study was to investigate the expression of cytokines in lymphocyte populations of patients with INS in comparison to healthy individuals, according to proteinuria. Methods: This cross-sectional study included 44 patients with INS and eight healthy children, matched for age and sex (controls). Patients were subdivided according to proteinuria: persistent proteinuria or partial remission (PP ≥ 300 mg/24 h, n = 17) and low proteinuria or complete remission (LP < 300 mg/24 h, n = 27). Ex vivo analysis of peripheral blood leukocytes by flow cytometry was performed using surface markers for T-lymphocytes, TCD4, TCD8, natural killer (NK) cells, NKT, and B-lymphocytes. Frequencies of intracellular cytokines were analyzed in these cells. Results: The frequencies of B-lymphocytes, NK cells, and NKT cells were lower in INS than in controls, whereas INS patients had a higher frequency of CD4+tumor necrosis factor (TNF)-α+ cells than controls. Cytotoxic-T-lymphocytes expressing IFN-γ were lower in INS than in controls. Patients with PP showed higher frequencies of CD4-T-lymphocytes expressing IFN-γ and TNF-α than controls. CD8-lymphocytes expressing TNF-α were increased in PP group when compared with LP and controls, while CD8+interferon (IFN)-γ+ cells were lower than in LP and in controls. Conclusion: Regardless the level of proteinuria, INS patients had increased expression of TNF-α in CD4-lymphocytes and reduced expression of IFN-γ in CD8-lymphocytes. Persistence of proteinuria was associated with higher levels of inflammatory markers.
Resumo Objetivo Há comprovação do importante papel das alterações no sistema imunológico no desencadeamento e manutenção da síndrome nefrótica idiopática (SNI). O objetivo deste estudo foi investigar a expressão das citocinas em populações de linfócitos de pacientes com SNI em comparação a indivíduos saudáveis e de acordo com a proteinúria. Métodos Este estudo transversal incluiu 44 pacientes com SNI e oito crianças saudáveis, pareados por idade e sexo (controles). Os pacientes foram subdivididos de acordo com a proteinúria: proteinúria persistente ou remissão parcial (PP ≥ 300 mg/24 h, n = 17) e proteinúria baixa ou remissão completa (PB < 300 mg/24 h, n = 27). A análise ex vivo de leucócitos no sangue periférico por citometria de fluxo foi feita utilizando marcadores de superfície para linfócitos T, TCD4, TCD8, células natural killer (NK), linfócitos NKT e B. As frequências das citocinas intracelulares foram analisadas nessas células. Resultados A frequência dos linfócitos B, células NK e células NKT foi menor em pacientes com SNI do que nos controles, ao passo que os pacientes com SNI apresentaram maior frequência de células CD4+fator de necrose tumoral (TNF)-α+ do que nos controles. Os linfócitos T citotóxicos que expressam interferon (IFN)-γ foram menores nos pacientes com SNI do que nos controles. Os pacientes com PP mostraram maiores frequências de linfócitos T CD4 que expressam IFN-γ e TNF-α que os controles. Os linfócitos CD8 que expressam TNF-α apresentaram aumento no grupo com PP, em comparação aos com PB e os controles, apesar de as células CD8+IFN-γ+ serem mais baixas nos pacientes com PB e nos controles. Conclusão Com relação ao nível de proteinúria, os pacientes com SNI apresentaram aumento na expressão de TNF-α nos linfócitos CD4 e expressão reduzida de IFN-γ nos linfócitos CD8. A persistência da proteinúria foi associada a maiores níveis de marcadores inflamatórios.
Subject(s)
Humans , Male , Female , Child , Adolescent , Proteinuria/etiology , Killer Cells, Natural/immunology , T-Lymphocytes/immunology , Cytokines/immunology , Nephrotic Syndrome/immunology , Proteinuria/immunology , Proteinuria/blood , Biomarkers , Case-Control Studies , Cross-Sectional Studies , Cytokines/blood , Disease Progression , Flow Cytometry , Leukocyte Count , Nephrotic Syndrome/complications , Nephrotic Syndrome/bloodABSTRACT
We report a 19 years old male presenting with knee pain, elevated liver enzymes and proteinuria. Further investigation found positive antinuclear and anti-smooth muscle antibodies and a liver biopsy revealed the presence of an autoimmune hepatitis. Treatment with corticosteroids and azathioprine was started, resulting in normalization of liver enzymes but proteinuria persisted and a kidney biopsy disclosed a focal segmental glomerulosclerosis. The use of lisinopril resulted in a significative reduction of proteinuria and, after 30 months of follow up, he continues with azathioprine, lisinopril and a low prednisone dose without evidence of liver or kidney disease activity.
Subject(s)
Humans , Male , Young Adult , Proteinuria/complications , Glomerulosclerosis, Focal Segmental/complications , Hepatitis, Autoimmune/complications , Proteinuria/diagnosis , Proteinuria/immunology , Proteinuria/drug therapy , Immunohistochemistry , Glomerulosclerosis, Focal Segmental/diagnosis , Glomerulosclerosis, Focal Segmental/immunology , Autoimmunity , Hepatitis, Autoimmune/diagnosis , Hepatitis, Autoimmune/immunology , Diagnosis, Differential , Kidney/pathology , Liver/pathologyABSTRACT
La preeclampsia es un trastorno multisistémico caracterizado por hipertensión inducida por el embarazo, asociada a proteinuria, edema e incremento de la permeabilidad vascular. Aparece en la segunda mitad de la gestación y es característicamente reversible en el post parto. Además puede presentar múltiples complicaciones llegando incluso a la muerte del feto o de su progenitora.De su fisiopatología aún en estudio, se ha podido concluir que es una sucesión multifactorial de eventos que se centran principalmente en dos etapas: la primera es una invasión placentaria pobre que conlleva una isquemia secundaria y una segunda etapa caracterizada por una activación endotelial y una respuesta autoinmune exagerada. Para cada una de estas etapas se han descrito múltiples alteraciones moleculares, las que se ven influidas tanto por la carga genética, factores maternos, paternos, del feto y también del ambiente.
Preeclampsia is a multisystemic disorder characterized by hypertension induced by the pregnancy, associated to proteinuria, edema and increase of the vascular permeability. It appears during the second half of gestation and is characteristically reversible during postpartum. In addition, it can elicit many complications including the death of the fetus or the mother. Of its physiopathology still in study, it has been possible to conclude that it is a multifactorial succession of events divided mainly in two stages: first there is a poor placental invasion that leads to secondary ischemia and the second stage is characterized by an endothelial activation and an exaggerated autoimmune response. For each one of these stages, multiple molecular alterations have been described, which are influenced by genetic load, maternal and father factors, fetal factors and also by environmental factors.