RESUMO
X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.
Assuntos
Proteínas de Transporte/genética , Infecções por Herpesviridae/complicações , Herpesvirus Humano 4 , Peptídeos e Proteínas de Sinalização Intracelular , Transtornos Linfoproliferativos/genética , Mutação , Domínios de Homologia de src/genética , Antígenos CD , Linfócitos B/imunologia , Linfócitos B/virologia , Proteínas de Transporte/metabolismo , Clonagem Molecular , Feminino , Ligação Genética , Glicoproteínas/metabolismo , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/virologia , Humanos , Imunoglobulinas/metabolismo , Transtornos Linfoproliferativos/complicações , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/virologia , Masculino , Dados de Sequência Molecular , Linhagem , Receptores de Superfície Celular , Alinhamento de Sequência , Deleção de Sequência , Proteína Associada à Molécula de Sinalização da Ativação Linfocitária , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária , Linfócitos T/imunologia , Linfócitos T/virologia , Cromossomo XRESUMO
A 5-month-old male presented with fever, hepatosplenomegaly, leukocytosis with atypical lymphoblasts, anemia and thrombocytopenia. Severe combined imunodeficiency syndrome (T-, B+, NK+), B lymphoproliferative disease and hemophagocytic lymphohistiocytosis triggered by Epstein-Barr virus (EBV) were diagnosed. As his clinical situation deteriorated rapidly, BMT was performed with unmanipulated marrow stem cells from his EBV-positive HLA-identical sister after conditioning with dexamethasone (1.75 mg/kg/day), cyclophosphamide (114 mg/kg) and etoposide (10 mg/kg), with no immunosuppression given post transplant. Engraftment occurred on day 6 with explosive proliferation of donor CD8(+) T cells. The patient died 3 days later from acute respiratory distress syndrome. Autopsy revealed full donor engraftment and no signs of hemophagocytic lymphohistiocytosis or B lymphoproliferative disease. Thus, transplanted T cells can expand very rapidly within days after BMT and clear EBV lymphoproliferative disease and hemophagocytic lymphohistiocytosis.