Heterozygous gain of function mutations in the gene encoding p110δ subunit of PI3K have been recently associated with activated PI3K-δ syndrome (APDS), a novel combined immune deficiency characterized by recurrent sinopulmonary infections, lymphopenia, reduced class-switched memory B cells, lymphadenopathy, CMV and/or EBV viremia and EBV-related lymphoma. Here we report a dominant gain of function PIK3CD mutation (E1021K) in a patient presenting with recurrent otitis media, massive splenomegaly, and persistent EBV-viraemia. The immunological studies showed low IgA level, but normal IgM, IgG, and normal antibody response to diphtheria and tetanus toxoid vaccination. Analysis of B lymphocyte subsets revealed abnormal expansion of transitional B cells, and low percentage of switched CD27+IgD− and CD27+IgD+ memory B cells. Analysis of T cell compartment unveiled prevalence of terminally differentiated cells. This study suggests that PIK3CD gain of function mutations should be suspected despite incomplete phenotype in patients with early onset splenomegaly, persistent EBV viremia and abnormal B and T cell subsets despite normal IgG levels. Currently the optimal treatment is still debated, but prompt management can hopefully diminish incidence of severe long-lasting sequelae (i.e. bronchiectasis, ear and sinus damage).

Saettini, F., Pelagatti, M., Sala, D., Moratto, D., Giliani, S., Badolato, R., et al. (2017). Early diagnosis of PI3Kδ syndrome in a 2 years old girl with recurrent otitis and enlarged spleen. IMMUNOLOGY LETTERS, 190, 279-281 [10.1016/j.imlet.2017.08.021].

Early diagnosis of PI3Kδ syndrome in a 2 years old girl with recurrent otitis and enlarged spleen

Saettini, F;Sala, D;Biondi, A
2017

Abstract

Heterozygous gain of function mutations in the gene encoding p110δ subunit of PI3K have been recently associated with activated PI3K-δ syndrome (APDS), a novel combined immune deficiency characterized by recurrent sinopulmonary infections, lymphopenia, reduced class-switched memory B cells, lymphadenopathy, CMV and/or EBV viremia and EBV-related lymphoma. Here we report a dominant gain of function PIK3CD mutation (E1021K) in a patient presenting with recurrent otitis media, massive splenomegaly, and persistent EBV-viraemia. The immunological studies showed low IgA level, but normal IgM, IgG, and normal antibody response to diphtheria and tetanus toxoid vaccination. Analysis of B lymphocyte subsets revealed abnormal expansion of transitional B cells, and low percentage of switched CD27+IgD− and CD27+IgD+ memory B cells. Analysis of T cell compartment unveiled prevalence of terminally differentiated cells. This study suggests that PIK3CD gain of function mutations should be suspected despite incomplete phenotype in patients with early onset splenomegaly, persistent EBV viremia and abnormal B and T cell subsets despite normal IgG levels. Currently the optimal treatment is still debated, but prompt management can hopefully diminish incidence of severe long-lasting sequelae (i.e. bronchiectasis, ear and sinus damage).
Articolo in rivista - Articolo scientifico
Hypogammaglobulinemia; Lymphopenia; Lymphoproliferation; Perisistant EBV viremia; PI3Kδ syndrome; B-Lymphocyte Subsets; Child, Preschool; Class I Phosphatidylinositol 3-Kinases; Early Diagnosis; Female; Humans; Immunologic Deficiency Syndromes; Lymphopenia; Mutation; Otitis; Phosphatidylinositol 3-Kinases; Respiratory Tract Infections; Sirolimus; Spleen; Splenomegaly; T-Lymphocyte Subsets
English
2017
190
279
281
none
Saettini, F., Pelagatti, M., Sala, D., Moratto, D., Giliani, S., Badolato, R., et al. (2017). Early diagnosis of PI3Kδ syndrome in a 2 years old girl with recurrent otitis and enlarged spleen. IMMUNOLOGY LETTERS, 190, 279-281 [10.1016/j.imlet.2017.08.021].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/239765
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