Clinical, molecular, and cellular immunologic findings in patients with SP110-associated veno-occlusive disease with immunodeficiency syndrome.
J Allergy Clin Immunol
; 130(3): 735-742.e6, 2012 Sep.
Article
em En
| MEDLINE
| ID: mdl-22621957
ABSTRACT
BACKGROUND:
Mutations in the SP110 gene result in infantile onset of the autosomal recessive primary immunodeficiency disease veno-occlusive disease with immunodeficiency syndrome (VODI), which is characterized by hypogammaglobulinemia, T-cell dysfunction, and a high frequency of hepatic veno-occlusive disease.OBJECTIVES:
We sought to further characterize the clinical features, B-lineage cellular immunologic findings, and molecular pathogenesis of this disorder in 9 patients with new diagnoses, including 4 novel mutations from families of Italian, Hispanic, and Arabic ethnic origin.METHODS:
Methods used include clinical review; Sanger DNA sequencing of the SP110 gene; determination of transfected mutant protein function by using immunofluorescent studies in Hep-2 cells; quantitation of B-cell subsets by means of flow cytometry; assessments of B-cell function after stimulation with CD40 ligand, IL-21, or both; and differential gene expression array studies of EBV-transformed B cells.RESULTS:
We confirm the major diagnostic criteria and the clinical utility of SP110 mutation testing for the diagnosis of VODI. Analysis of 4 new alleles confirms that VODI is caused by reduced functional SP110 protein levels. Detailed B-cell immunophenotyping demonstrated that Sp110 deficiency compromises the ability of human B cells to respond to T cell-dependent stimuli and differentiate into immunoglobulin-secreting cells in vitro. Expression microarray studies have identified pathways involved in B-lymphocyte differentiation and macrophage function.CONCLUSION:
These studies show that a range of mutations in SP110 that cause decreased SP110 protein levels and impaired late B-cell differentiation cause VODI and that the condition is not restricted to the Lebanese population.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hepatopatia Veno-Oclusiva
/
Proteínas Nucleares
/
Síndromes de Imunodeficiência
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Child
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Child, preschool
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Humans
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Infant
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2012
Tipo de documento:
Article