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Activated Phosphoinositide 3-Kinase δ Syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F23%3A10465703" target="_blank" >RIV/00064203:_____/23:10465703 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11130/23:10465703

  • Result on the web

    <a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=rbwc7WkZ4C" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=rbwc7WkZ4C</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.jaci.2023.06.015" target="_blank" >10.1016/j.jaci.2023.06.015</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Activated Phosphoinositide 3-Kinase δ Syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity

  • Original language description

    BACKGROUND: Activated phosphoinositide-3-kinase (PI3K) δ Syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking. OBJECTIVES: Report the extended spectrum of disease manifestations in APDS1 versus APDS2, compare these to CTLA-4 deficiency, NFκB1 deficiency, and STAT3 gain-of-function (GOF) disease; identify predictors of severity in APDS. METHODS: Data collection with the European Society for Immunodeficiencies (ESID)-APDS registry. Comparison with published cohorts of the other IEIs. RESULTS: The analysis of 170 APDS patients outlines high penetrance and early-onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA-4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS. CONCLUSION: APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEI is substantial. Some specific features distinguish APDS1 from APDS2. Early-onset is a risk factor for severe disease course calling for specific treatment studies in younger patients.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30102 - Immunology

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2023

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    Journal of Allergy and Clinical Immunology

  • ISSN

    0091-6749

  • e-ISSN

    1097-6825

  • Volume of the periodical

    152

  • Issue of the periodical within the volume

    4

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    13

  • Pages from-to

    984-996

  • UT code for WoS article

    001088480400001

  • EID of the result in the Scopus database

    2-s2.0-85169451330