Portal de Periódicos da CAPES

Reduced thymic output, cell cycle abnormalities, and increased apoptosis of T lymphocytes in patients with cartilage-hair hypoplasia

2011; Elsevier BV; Volume: 128; Issue: 1 Linguagem: Inglês

10.1016/j.jaci.2011.03.042

1097-6825

Miguel Á. de la Fuente, Mike Recher, Nicholas L. Rider, Kevin A. Strauss, D. Holmes Morton, Margaret Adair, Francisco A. Bonilla, Hans D. Ochs, Erwin W. Gelfand, Itai M. Pessach, Jolán E. Walter, Alejandra King, Silvia Giliani, Sung‐Yun Pai, Luigi D. Notarangelo,

Respiratory viral infections research

BackgroundCartilage-hair hypoplasia (CHH) is characterized by metaphyseal dysplasia, bone marrow failure, increased risk of malignancies, and a variable degree of immunodeficiency. CHH is caused by mutations in the RNA component of the mitochondrial RNA processing (RMRP) endoribonuclease gene, which is involved in ribosomal assembly, telomere function, and cell cycle control.ObjectivesWe aimed to define thymic output and characterize immune function in a cohort of patients with molecularly defined CHH with and without associated clinical immunodeficiency.MethodsWe studied the distribution of B and T lymphocytes (including recent thymic emigrants), in vitro lymphocyte proliferation, cell cycle, and apoptosis in 18 patients with CHH compared with controls.ResultsPatients with CHH have a markedly reduced number of recent thymic emigrants, and their peripheral T cells show defects in cell cycle control and display increased apoptosis, resulting in poor proliferation on activation.ConclusionThese data confirm that RMRP mutations result in significant defects of cell-mediated immunity and provide a link between the cellular phenotype and the immunodeficiency in CHH. Cartilage-hair hypoplasia (CHH) is characterized by metaphyseal dysplasia, bone marrow failure, increased risk of malignancies, and a variable degree of immunodeficiency. CHH is caused by mutations in the RNA component of the mitochondrial RNA processing (RMRP) endoribonuclease gene, which is involved in ribosomal assembly, telomere function, and cell cycle control. We aimed to define thymic output and characterize immune function in a cohort of patients with molecularly defined CHH with and without associated clinical immunodeficiency. We studied the distribution of B and T lymphocytes (including recent thymic emigrants), in vitro lymphocyte proliferation, cell cycle, and apoptosis in 18 patients with CHH compared with controls. Patients with CHH have a markedly reduced number of recent thymic emigrants, and their peripheral T cells show defects in cell cycle control and display increased apoptosis, resulting in poor proliferation on activation. These data confirm that RMRP mutations result in significant defects of cell-mediated immunity and provide a link between the cellular phenotype and the immunodeficiency in CHH.