RESUMO
Autoimmune lymphoproliferative syndrome (ALPS) is characterized by splenomegaly, lymphadenopathy, hypergammaglobulinemia, accumulation of double-negative TCRalphabeta(+) CD4(-)CD8(-) T cells (DNT cells), and autoimmunity. Previously, DNT cell detection and a functional defect of T cells in a FAS-induced apoptosis test in vitro had been used for ALPS diagnosis. However, a functional defect can also be detected in mutation-positive relatives (MPRs) who remain free of any ALPS-related disease. In contrast, lymphocytes from patients carrying a somatic mutation of FAS exhibit normal sensitivity to FAS-induced apoptosis in vitro. We assessed the soluble FAS-L concentration in the plasma of ALPS patients carrying FAS mutations. Overall, we showed that determination of the FAS-L represents, together with the IL-10 concentration and the DNT cell percentage, a reliable tool for the diagnosis of ALPS.
Assuntos
Doenças Autoimunes/diagnóstico , Proteína Ligante Fas/metabolismo , Interleucina-10/metabolismo , Transtornos Linfoproliferativos/diagnóstico , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Linfócitos T/metabolismo , Receptor fas/genética , Adolescente , Adulto , Doenças Autoimunes/sangue , Doenças Autoimunes/genética , Doenças Autoimunes/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Antígenos CD4/sangue , Antígenos CD4/metabolismo , Antígenos CD8/sangue , Antígenos CD8/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Proteína Ligante Fas/sangue , Humanos , Lactente , Recém-Nascido , Interleucina-10/sangue , Transtornos Linfoproliferativos/sangue , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/metabolismo , Pessoa de Meia-Idade , Mutação/fisiologia , Síndrome , Linfócitos T/patologia , Adulto Jovem , Receptor fas/fisiologiaRESUMO
Exhaled nitric oxide (eNO) levels are correlated with several markers of atopy and inflammatory activity in the airways, but the relationship between eNO and total serum IgE has not been fully elucidated in the context of allergic sensitization. The aim of this study was to investigate the relationship between eNO, total serum IgE and allergic sensitization in childhood asthma and allergic rhinitis. eNO levels, lung function, skin prick tests and total serum IgE were determined in 109 children (mean age, 10.4 yr) with mild intermittent asthma and in 41 children (mean age, 10.1 yr) with allergic rhinitis; 25 healthy non-atopic children were recruited as controls. eNO levels (median) were significantly higher in patients with asthma (22.7 p.p.b.) and in those with allergic rhinitis (15.3 p.p.b.) than in healthy controls (5.9 p.p.b.). Children with allergic asthma had higher eNO levels than children with allergic rhinitis. A significant positive correlation was found between eNO and total serum IgE (asthma, r = 0.42, p < 0.0001; allergic rhinitis, r = 0.31, p < 0.01), and between eNO and the number of positive skin prick tests (asthma, r = 0.31, p < 0.0001; allergic rhinitis, r = 0.39, p < 0.01). eNO levels were better correlated with total IgE than with the number of positive skin prick tests. This correlation was independent of allergic sensitization. High total serum IgE represents a specific and predictive marker of eNO increase in children with asthma or allergic rhinitis. This finding adds further support to the hypothesis that increased serum IgE could be a marker itself of airway inflammation in patients with allergic disease.
