RESUMO
X-linked agammaglobulinemia (XLA) has been associated with a broad range of infections, but enteroviral disease represents one of the most damaging infections. The risk of enteroviral infection in XLA is lower now than in the setting of intramuscular immunoglobulin or in patients without immunoglobulin replacement, but the rate of infection has not declined significantly in the era of intravenous immunoglobulin replacement. Enteroviruses can cause inflammation of nearly every organ, but in XLA, infections often manifest as dermatomyositis or chronic meningoencephalitis. Difficulty and delay in recognizing symptoms and lack of specific therapy contribute to the poor outcomes. Furthermore, cerebrospinal fluid detection of enteroviruses is not very sensitive. Reluctance to perform brain biopsies can lead to significant delays. The other feature compromising outcomes is the lack of specific therapy. High-dose peripheral and intraventricular immunoglobulin have been used, but failure is still common. New antienteroviral drugs are in development and show promise for immunodeficient patients with life-threatening infections with enterovirus.
Assuntos
Agamaglobulinemia , Infecções por Enterovirus , Doenças Genéticas Ligadas ao Cromossomo X , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/tratamento farmacológico , Agamaglobulinemia/epidemiologia , Agamaglobulinemia/virologia , Antivirais/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/virologia , Pré-Escolar , Enterovirus/genética , Enterovirus/isolamento & purificação , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/tratamento farmacológico , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/virologia , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/tratamento farmacológico , Doenças Genéticas Ligadas ao Cromossomo X/epidemiologia , Doenças Genéticas Ligadas ao Cromossomo X/virologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Éteres Fenílicos/uso terapêuticoRESUMO
UNLABELLED: We have analysed the phenotype of T lymphocytes in two X-linked lymphoproliferative disease (XLP) patients with the same SH2D1A mutation differing in initial exposure to Epstein-Barr virus (EBV) and treatment. While memory T lymphocytes (with low CCR7 and CD62L expression) prevailed in both XLP patients, in patient 9, who developed acute infectious mononucleosis (AIM) and received B cell ablative treatment, the predominant phenotype was that of late effector CD8 T cells (CD27-, CD28-, CCR7-, CD62L-, CD45 RA+, perforin+), while in patient 4 (who did not suffer AIM) the prevalent phenotype of CD8 T lymphocytes was similar to that of normal controls (N) or to that of adult individuals who recovered from AIM: CD27+ , CD28+, CCR7-, CD62L-, CD45 RO+ and perforin-. CD57 expression (related to senescence) was also higher in CD8 T cells from patient 9 than in patient 4, AIM or N. Persistently high EBV viral load was observed in patient 9. The results obtained from this limited number of XLP patients suggest that events related to the initial EBV encounter (antigen load, treatment, cytokine environment) may have more weight than lack of SH2D1A in determining the long-term differentiation pattern of CD8 memory T cells.