RESUMO
Banked unrelated umbilical cord blood matched at 5 of 6 human leukocyte antigen loci was used to reconstitute the immune system in 2 brothers with X-linked lymphoproliferative syndrome and 1 boy with X-linked hyperimmunoglobulin-M syndrome. Pretransplant cytoreduction and posttransplant graft-versus-host prophylaxis were given. Hematopoietic engraftment and correction of the genetic defects were documented by molecular techniques. Two years after transplantation, all 3 patients have normal immune systems. These reports support the wider use of banked partially matched cord blood for transplantation in primary immunodeficiencies.
Assuntos
Sangue Fetal/citologia , Transplante de Células-Tronco Hematopoéticas/métodos , Transtornos Linfoproliferativos/terapia , Ligante de CD40/genética , Criança , Pré-Escolar , Análise Mutacional de DNA/métodos , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Lactente , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/imunologia , Masculino , Linfócitos T/imunologiaRESUMO
We describe 5 children from 2 families with mutations in the CD40 ligand (CD40L) gene leading to absent expression of CD40L on activated CD4 cells. All subjects presented with interstitial pneumonia with low serum IgG and normal serum IgM. One child had normal and one child had elevated serum IgA. Four had confirmed Pneumocystis carinii pneumonia. In spite of intravenous immunoglobulin treatment yielding therapeutic serum immunoglobulin levels, 3 children had enteroviral encephalitis. When assessed by flow cytometry, the 3 surviving affected male children had absent CD40L expression on activated CD4(+) T cells. The affected children from both families were shown to have the same single nucleotide insertion (codon 131) resulting in frameshift and early termination within exon 4 (extracellular domain). This observation demonstrates that persistent enteroviral infection is not only observed in X-linked agammaglobulinemia but may also occur in patients with X-linked hyper IgM syndrome.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Antígenos CD40/imunologia , Infecções por Enterovirus/etiologia , Hipergamaglobulinemia/complicações , Hipergamaglobulinemia/genética , Imunoglobulina M/sangue , Glicoproteínas de Membrana/genética , Meningoencefalite/etiologia , Mutação , Ligante de CD40 , Análise Mutacional de DNA , Citometria de Fluxo , Ligação Genética , Humanos , Hipergamaglobulinemia/terapia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Ligantes , Ativação Linfocitária , Masculino , Linhagem , Pneumonia por Pneumocystis/complicações , Reação em Cadeia da Polimerase , Síndrome , Cromossomo XRESUMO
We examined T-cell proliferation in five patients with X-linked hyper-IgM syndrome (XHIM), using a panel of antigens and lectins. All patients had impaired antigen-induced proliferation, whereas their lectin responses were normal. Thus, in addition to severely depressed antibody responses, patients with XHIM have a defect in antigen-specific T-cell proliferation, which may explain their susceptibility to pathogens such as Pneumocystis carinii.