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

Autor: Ma Pelagatti, Silvia Giliani, Francesco Saettini, Daniele Moratto, Raffaele Badolato, Andrea Biondi, D Sala
Přispěvatelé: Saettini, F, Pelagatti, M, Sala, D, Moratto, D, Giliani, S, Badolato, R, Biondi, A
Rok vydání: 2017
Předmět:
0301 basic medicine
Pathology
Immunoglobulin D
Hypogammaglobulinemia
Phosphatidylinositol 3-Kinases
T-Lymphocyte Subsets
Early Diagnosi
Respiratory Tract Infection
Immunology and Allergy
Sirolimu
Otitis
Respiratory Tract Infections
Class I Phosphatidylinositol 3-Kinase
Immunologic Deficiency Syndrome
biology
Lymphoproliferation
medicine.anatomical_structure
Child
Preschool
Female
Perisistant EBV viremia
medicine.symptom
Human
medicine.medical_specialty
Class I Phosphatidylinositol 3-Kinases
Primary Immunodeficiency Diseases
T cell
Immunology
B-Lymphocyte Subsets
Spleen
03 medical and health sciences
Immune system
Lymphopenia
medicine
Humans
PI3Kδ syndrome
B-Lymphocyte Subset
Sirolimus
business.industry
Immunologic Deficiency Syndromes
medicine.disease
Otiti
Lymphoma
Early Diagnosis
030104 developmental biology
P110δ
Mutation
Splenomegaly
biology.protein
Phosphatidylinositol 3-Kinase
business
Zdroj: Immunology Letters. 190:279-281
ISSN: 0165-2478
DOI: 10.1016/j.imlet.2017.08.021
Popis: 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).
Databáze: OpenAIRE
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