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Review
. 2011 Jan;163(1):96-103.
doi: 10.1111/j.1365-2249.2010.04280.x. Epub 2010 Nov 9.

Do ribosomopathies explain some cases of common variable immunodeficiency?

S Khan  1 , J Pereira, P J Darbyshire, S Holding, P C Doré, W A C Sewell, A Huissoon
Affiliations
Review

Do ribosomopathies explain some cases of common variable immunodeficiency?

S Khan et al. Clin Exp Immunol. 2011 Jan.

Abstract

The considerable clinical heterogeneity of patients with common variable immunodeficiency disorders (CVID) shares some similarity with bone-marrow failure disorders such as Diamond-Blackfan anaemia (DBA) and Shwachman-Diamond syndrome (SDS), now recognized as defects in ribosome biogenesis or ribosomopathies. The recognition of a patient with DBA who subsequently developed CVID lends support to our previous finding of a heterozygous mutation in the SBDS gene of SBDS in another CVID patient, suggesting that ribosome biogenesis defects are responsible for a subset of CVID. Genetic defects in the ribosomal translational machinery responsible for various bone marrow failure syndromes are recognized readily when they manifest in children, but diagnosing these in adults presenting with complex phenotypes and hypogammaglobulinaemia can be a challenge. In this perspective paper, we discuss our clinical experience in CVID patients with ribosomopathies, and review the immunological abnormalities in other conditions associated with ribosomal dysfunction. With genetic testing available for various bone marrow failure syndromes, our hypothesis that ribosomal abnormalities may be present in patients with CVID could be proved in future studies by testing for mutations in specific ribosomal genes. New knowledge might then be translated into novel therapeutic strategies for patients in this group of immunodeficiency disorders.

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Figures

Fig. 1
Fig. 1
An overview of the biogenesis of the eukaryotic ribosome. Synthesis of ribosomal proteins and assembly of the mature eukaryotic ribosome has several step: (1) DNA transcription and RNA processing; (2) translation of ribosomal RNA (rRNA); (3) modification and processing by small nucleolar RNPs (snoRNPs) and Rnase; (4) formation of immature large and small ribosomal subunits and exit from nucleolus; and (5) formation of mature eukaryotic ribosome[8]. The 60S subunit has a cleft for tRNA and amino acids from the endoplasmic reticulum (ER) are translated into protein. rRNA, ribosomal RNA; mRNA, messenger RNA; tRNA, transfer RNA; AAA, amino acids.
Fig. 3
Fig. 3
Multiplex ligand-dependent probe amplification (MLPA) results of the RPS19 gene.
Fig. 2
Fig. 2
Sequencing results showing the polymorphisms found in the RPS24, RPL11 and RPS17 genes.
See this image and copyright information in PMC

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