Do ribosomopathies explain some cases of common variable immunodeficiency?
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.
Department of Immunology, Frimley Park Hospital NHS Foundation Trust, Portsmouth Road, Frimley, Camberley, Surrey, UK. sujoy.khan@fph-tr.nhs.uk
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S
Khan
J
J
Pereira
P J
PJ
Darbyshire
S
S
Holding
P C
PC
Doré
W A C
WA
Sewell
A
A
Huissoon
D000361:Agammaglobulinemia / Q000175:diagnosis / Q000235:genetics; D000368:Aged; D029503:Anemia, Diamond-Blackfan / Q000175:diagnosis / Q000235:genetics*; D001855:Bone Marrow Diseases / Q000175:diagnosis / Q000235:genetics; D017074:Common Variable Immunodeficiency / Q000175:diagnosis / Q000235:genetics*; D010188:Exocrine Pancreatic Insufficiency / Q000175:diagnosis / Q000235:genetics; D005260:Female; D006801:Humans; D008068:Lipomatosis; D008297:Male; D009154:Mutation; D011506:Proteins / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics; D012270:Ribosomes / Q000235:genetics* / Q000276:immunology*; D000081003:Shwachman-Diamond Syndrome; D016896:Treatment Outcome; D055815:Young Adult
D011506:Proteins; D012269:Ribosomal Proteins; C470521:SBDS protein, human; C040343:ribosomal protein S19