Back to Search
Start Over
Mutations in PIK3CD Can Cause Hyper IgM Syndrome (HIGM) Associated with Increased Cancer Susceptibility
- Source :
- Journal of Clinical Immunology. 34:272-276
- Publication Year :
- 2014
- Publisher :
- Springer Science and Business Media LLC, 2014.
-
Abstract
- Autosomal dominant gain of function mutations in the gene encoding PI3K p110δ 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.
- Subjects :
- Adult
Male
Heterozygote
Hyper IgM syndrome
Class I Phosphatidylinositol 3-Kinases
Biopsy
Hyper-IgM Immunodeficiency Syndrome
Immunology
Activated PI3K-delta syndrome
Biology
medicine.disease_cause
Article
Young Adult
Neoplasms
medicine
Humans
Immunology and Allergy
Genetic Predisposition to Disease
Child
B cell
Immunodeficiency
medicine.disease
Epstein–Barr virus
Pedigree
medicine.anatomical_structure
Immunoglobulin class switching
Mutation
biology.protein
Female
Lymph Nodes
Antibody
Subjects
Details
- ISSN :
- 15732592 and 02719142
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Immunology
- Accession number :
- edsair.doi.dedup.....e521a869b9cb2a3e758dd191599184b4