Journal
JOURNAL OF CLINICAL IMMUNOLOGY
Volume 34, Issue 3, Pages 272-276Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10875-014-0012-9
Keywords
Immunodeficiency; hyper IgM; PI3K; lymphoma; cancer susceptibility; epstein-barr virus
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Funding
- Intramural NIH HHS [Z99 CL999999] Funding Source: Medline
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Autosomal dominant gain of function mutations in the gene encoding PI3K p110 delta were recently associated with a novel combined immune deficiency characterized by recurrent sinopulmonary infections, CD4 lymphopenia, reduced class-switched memory B cells, lymphadenopathy, CMV and/or EBV viremia and EBV-related lymphoma. A subset of affected patients also had elevated serum IgM. Here we describe three patients in two families who were diagnosed with HIGM at a young age and were recently found to carry heterozygous mutations in PIK3CD. These patients had an abnormal circulating B cell distribution featuring a preponderance of early transitional (T1) B cells and plasmablasts. When stimulated in vitro, PIK3CD mutated B cells were able to secrete class-switched immunoglobulins. This finding implies that the patients' elevated serum IgM levels were unlikely a product of an intrinsic B cell functional inability to class switch. All three patients developed malignant lymphoproliferative syndromes that were not associated with EBV. Thus, we identified a novel subset of patients with PIK3CD mutations associated with HIGM, despite indications of preserved in vitro B cell class switch recombination, as well as susceptibility to non-EBV-associated malignancies.
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