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Natural Course of Activated Phosphoinositide 3-Kinase Delta Syndrome in Childhood and Adolescence
Activated phosphoinositide 3-kinase delta syndrome (APDS), caused by mutations in PI3Kδ catalytic p110δ (PIK3CD) or regulatory p85α (PIK3R1) subunits, is a primary immunodeficiency affecting both humoral and cellular immunity, which shares some phenotypic similarities with hyper-IgM syndromes and co...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326455/ https://www.ncbi.nlm.nih.gov/pubmed/34350147 http://dx.doi.org/10.3389/fped.2021.697706 |
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author | Bloomfield, Marketa Klocperk, Adam Zachova, Radana Milota, Tomas Kanderova, Veronika Sediva, Anna |
author_facet | Bloomfield, Marketa Klocperk, Adam Zachova, Radana Milota, Tomas Kanderova, Veronika Sediva, Anna |
author_sort | Bloomfield, Marketa |
collection | PubMed |
description | Activated phosphoinositide 3-kinase delta syndrome (APDS), caused by mutations in PI3Kδ catalytic p110δ (PIK3CD) or regulatory p85α (PIK3R1) subunits, is a primary immunodeficiency affecting both humoral and cellular immunity, which shares some phenotypic similarities with hyper-IgM syndromes and common variable immunodeficiency (CVID). Since its first description in 2013, over 200 patients have been reported worldwide. Unsurprisingly, many of the newly diagnosed patients were recruited later in life from previously long-standing unclassified immunodeficiencies and the early course of the disease is, therefore, often less well-described. In this study, we report clinical and laboratory features of eight patients followed for APDS, with particular focus on early warning signs, longitudinal development of their symptoms, individual variations, and response to therapy. The main clinical features shared by our patients included recurrent bacterial and viral respiratory tract infections, gastrointestinal disease, non-malignant lymphoproliferation, autoimmune thyroiditis, and susceptibility to EBV. All patients tolerated vaccination with both attenuated live and subunit vaccines with no adverse effects, although some failed to mount adequate antibody response. Laboratory findings were characterized by dysgammaglobulinaemia, elevated serum IgM, block in B-cell maturation with high transitional B cells, and low naïve T cells with CD8 T-cell activation. All patients benefited from immunoglobulin replacement therapy, whereas immunosuppression with mTOR pathway inhibitors was only partially successful. Therapy with specific PI3K inhibitor leniolisib was beneficial in all patients in the clinical trial. These vignettes, summary data, and particular tell-tale signs should serve to facilitate early recognition, referral, and initiation of outcome-improving therapy. |
format | Online Article Text |
id | pubmed-8326455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83264552021-08-03 Natural Course of Activated Phosphoinositide 3-Kinase Delta Syndrome in Childhood and Adolescence Bloomfield, Marketa Klocperk, Adam Zachova, Radana Milota, Tomas Kanderova, Veronika Sediva, Anna Front Pediatr Pediatrics Activated phosphoinositide 3-kinase delta syndrome (APDS), caused by mutations in PI3Kδ catalytic p110δ (PIK3CD) or regulatory p85α (PIK3R1) subunits, is a primary immunodeficiency affecting both humoral and cellular immunity, which shares some phenotypic similarities with hyper-IgM syndromes and common variable immunodeficiency (CVID). Since its first description in 2013, over 200 patients have been reported worldwide. Unsurprisingly, many of the newly diagnosed patients were recruited later in life from previously long-standing unclassified immunodeficiencies and the early course of the disease is, therefore, often less well-described. In this study, we report clinical and laboratory features of eight patients followed for APDS, with particular focus on early warning signs, longitudinal development of their symptoms, individual variations, and response to therapy. The main clinical features shared by our patients included recurrent bacterial and viral respiratory tract infections, gastrointestinal disease, non-malignant lymphoproliferation, autoimmune thyroiditis, and susceptibility to EBV. All patients tolerated vaccination with both attenuated live and subunit vaccines with no adverse effects, although some failed to mount adequate antibody response. Laboratory findings were characterized by dysgammaglobulinaemia, elevated serum IgM, block in B-cell maturation with high transitional B cells, and low naïve T cells with CD8 T-cell activation. All patients benefited from immunoglobulin replacement therapy, whereas immunosuppression with mTOR pathway inhibitors was only partially successful. Therapy with specific PI3K inhibitor leniolisib was beneficial in all patients in the clinical trial. These vignettes, summary data, and particular tell-tale signs should serve to facilitate early recognition, referral, and initiation of outcome-improving therapy. Frontiers Media S.A. 2021-07-19 /pmc/articles/PMC8326455/ /pubmed/34350147 http://dx.doi.org/10.3389/fped.2021.697706 Text en Copyright © 2021 Bloomfield, Klocperk, Zachova, Milota, Kanderova and Sediva. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pediatrics Bloomfield, Marketa Klocperk, Adam Zachova, Radana Milota, Tomas Kanderova, Veronika Sediva, Anna Natural Course of Activated Phosphoinositide 3-Kinase Delta Syndrome in Childhood and Adolescence |
title | Natural Course of Activated Phosphoinositide 3-Kinase Delta Syndrome in Childhood and Adolescence |
title_full | Natural Course of Activated Phosphoinositide 3-Kinase Delta Syndrome in Childhood and Adolescence |
title_fullStr | Natural Course of Activated Phosphoinositide 3-Kinase Delta Syndrome in Childhood and Adolescence |
title_full_unstemmed | Natural Course of Activated Phosphoinositide 3-Kinase Delta Syndrome in Childhood and Adolescence |
title_short | Natural Course of Activated Phosphoinositide 3-Kinase Delta Syndrome in Childhood and Adolescence |
title_sort | natural course of activated phosphoinositide 3-kinase delta syndrome in childhood and adolescence |
topic | Pediatrics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326455/ https://www.ncbi.nlm.nih.gov/pubmed/34350147 http://dx.doi.org/10.3389/fped.2021.697706 |
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