Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: a large patient cohort study

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Abstract: Background
Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ).

Objective
We sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort.

Methods
We applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS.

Results
Recurrent sinopulmonary infections (98%) and nonneoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3Kδ in the central nervous system; consistent with this, PI3Kδ is broadly expressed in the developing murine central nervous system. Thoracic imaging revealed high rates of mosaic attenuation (90%) and bronchiectasis (60%). Increased IgM levels (78%), IgG deficiency (43%), and CD4 lymphopenia (84%) were significant immunologic features. No immunologic marker reliably predicted clinical severity, which ranged from asymptomatic to death in early childhood. The majority of patients received immunoglobulin replacement and antibiotic prophylaxis, and 5 patients underwent hematopoietic stem cell transplantation. Five patients died from complications of APDS.

Conclusion
APDS is a combined immunodeficiency with multiple clinical manifestations, many with incomplete penetrance and others with variable expressivity. The severity of complications in some patients supports consideration of hematopoietic stem cell transplantation for severe childhood disease. Clinical trials of selective PI3Kδ inhibitors offer new prospects for APDS treatment

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Notes: The journal of allergy and clinical immunology. - 139, 2 (2017) , 597-606.e4, ISSN: 1097-6825

Event: Veröffentlichung

(where): Freiburg

(who): Universität

(when): 2021

Creator: Coulter, Tanya I.
Ehl, Stephan
Speckmann, Carsten
Grimbacher, Bodo
Condliffe, Alison M.
Cant, Andrew

DOI: 10.1016/j.jaci.2016.06.021

URN: urn:nbn:de:bsz:25-freidok-1760987

Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 25.03.2025, 1:45 PM CET

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Associated

Coulter, Tanya I.
Ehl, Stephan
Speckmann, Carsten
Grimbacher, Bodo
Condliffe, Alison M.
Cant, Andrew
Universität

Time of origin

2021

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Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: a large patient cohort study

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Other Objects (12)

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