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

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• 作者：Miguel A. de la Fuente MD ; PhD^a ; ^* ; Mike Recher MD^a ; ^* ; Nicholas L. Rider DO^c ; Kevin A. Strauss MD^c ; ^h ; D. Holmes Morton MD^c ; ^h ; Margaret Adair MD^d ; Francisco A. Bonilla MD ; PhD^a ; Hans D. Ochs MD^e ; Erwin W. Gelfand MD^d ; Itai M. Pessach MD ; PhD^a ; Jolan E. Walter MD ; PhD^a ; Alejandra King MD^f ; Silvia Giliani PhD^g ; Sung-Yun Pai MD^b ; Luigi D. Notarangelo MD^a ; ^{luigi.notarangelo@childrens.harvard.edu"" rel=""nofollow}
• 关键词：Cartilage-hair hypoplasia ; RMRP ; immunodeficiency ; T  ; lymphocytes ; thymus ; cell cycle ; apoptosis
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2011
• 出版时间：July 2011
• 年：2011
• 卷：128
• 期：1
• 页码：139-146
• 全文大小：996 K

文摘

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.