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J Allergy Clin Immunol. 2011 Jul;128(1):139-146. doi: 10.1016/j.jaci.2011.03.042. Epub 2011 May 13.

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

Author information

1
Division of Immunology and the Manton Center for Orphan Disease Research.
2
Clinic for Special Children, Strasburg.
3
Department of Biology, Franklin and Marshall College, Lancaster.
4
Department of Pediatrics, National Jewish Health, Denver.
5
Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Research Institute.
6
Immunology Unit, Hospital Luis Calvo Mackenna, Santiago.
7
"Angelo Nocivelli" Institute for Molecular Medicine and Department of Pediatrics, University of Brescia.
8
Division of Hematology, Children's Hospital Boston.
#
Contributed equally

Abstract

BACKGROUND:

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.

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

PMID:
21570718
PMCID:
PMC4287238
DOI:
10.1016/j.jaci.2011.03.042
[Indexed for MEDLINE]
Free PMC Article
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