Natural Course of Activated Phosphoinositide 3-Kinase Delta Syndrome in Childhood and Adolescence

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064190%3A_____%2F21%3AN0000142" target="_blank" >RIV/00064190:_____/21:N0000142 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/21:10429942 RIV/00064203:_____/21:10429942 RIV/00216208:11110/21:10429942

Result on the web

<a href="https://doi.org/10.3389/fped.2021.697706" target="_blank" >https://doi.org/10.3389/fped.2021.697706</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fped.2021.697706" target="_blank" >10.3389/fped.2021.697706</a>

Result language

angličtina

Original language name

Natural Course of Activated Phosphoinositide 3-Kinase Delta Syndrome in Childhood and Adolescence

Original language 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.

Czech name

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Czech description

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Type

J_SC - Article in a specialist periodical, which is included in the SCOPUS database

CEP classification

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OECD FORD branch

30209 - Paediatrics

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

FRONTIERS IN PEDIATRICS

ISSN

2296-2360

e-ISSN

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Volume of the periodical

9

Issue of the periodical within the volume

19.7.2021

Country of publishing house

CH - SWITZERLAND

Number of pages

12

Pages from-to

Article number 697706

UT code for WoS article

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EID of the result in the Scopus database

2-s2.0-85111934893