TY - JOUR
T1 - Clinical Manifestations and Outcomes of Activated Phosphoinositide 3-Kinase δ Syndrome from the USIDNET Cohort
AU - Oh, Jessica
AU - Garabedian, Elizabeth
AU - Fuleihan, Ramsay
AU - Cunningham-Rundles, Charlotte
N1 - Funding Information:
This work was supported by the National Institutes of Health (grant nos. AI-061093 , AI-086037 , and AI-48693 ) and the David S. Gottesman Immunology Chair.
Publisher Copyright:
© 2021 American Academy of Allergy, Asthma & Immunology
PY - 2021/11
Y1 - 2021/11
N2 - Background: Activated phosphoinositide 3-kinase δ syndrome is a combined primary immunodeficiency characterized by gain-of-function mutations in PIK3CD and PIK3R1. Activated phosphoinositide 3-kinase δ syndrome demonstrates a large range of phenotypes including respiratory and herpesvirus infections, lymphadenopathy, autoimmunity, and developmental delay. Objective: To describe clinical phenotypes and disease outcomes of a large activated phosphoinositide 3-kinase δ syndrome cohort from the United States Immunodeficiency Network Registry. Methods: A total of 38 patients were enrolled in the United States Immunodeficiency Network Registry, and 2 additional patients were obtained from the Clinical Immunology Division at Mount Sinai Hospital. Each patient's demographic characteristics, disease complications, genetic studies, laboratory data, therapeutic interventions, and clinical outcomes were reviewed. Results: There was a high frequency of respiratory infections (70.0% pneumonia) and herpesvirus infections (37.5%). Bronchiectasis was observed in 45.0% of patients. Lymphadenopathy was common (52.5%), and 12.5% of patients developed lymphoma. Neurological and developmental findings were common: 20.0% had developmental delay, 15.0% had seizures, and 10.0% had dysmorphic features. Asthma was more common in PIK3CD compared with PIK3R1 patients (63.6% vs 14.3%). More subjects with PIK3CD had CD3 lymphopenia compared with the PIK3R1 cohort. Seven patients underwent hematopoietic stem cell transplantation. One patient died from infectious complications. Conclusions: This is the first cohort comparing clinical manifestations in PIK3CD and PIK3R1 patients from the USIDNET Registry. Similar frequencies of respiratory and herpesvirus infections, lymphadenopathy, and developmental delay were observed compared with previous cohort studies. However, a higher frequency of asthma and CD3 lymphopenia in the PIK3CD cohort compared with the PIK3R1 cohort was observed.
AB - Background: Activated phosphoinositide 3-kinase δ syndrome is a combined primary immunodeficiency characterized by gain-of-function mutations in PIK3CD and PIK3R1. Activated phosphoinositide 3-kinase δ syndrome demonstrates a large range of phenotypes including respiratory and herpesvirus infections, lymphadenopathy, autoimmunity, and developmental delay. Objective: To describe clinical phenotypes and disease outcomes of a large activated phosphoinositide 3-kinase δ syndrome cohort from the United States Immunodeficiency Network Registry. Methods: A total of 38 patients were enrolled in the United States Immunodeficiency Network Registry, and 2 additional patients were obtained from the Clinical Immunology Division at Mount Sinai Hospital. Each patient's demographic characteristics, disease complications, genetic studies, laboratory data, therapeutic interventions, and clinical outcomes were reviewed. Results: There was a high frequency of respiratory infections (70.0% pneumonia) and herpesvirus infections (37.5%). Bronchiectasis was observed in 45.0% of patients. Lymphadenopathy was common (52.5%), and 12.5% of patients developed lymphoma. Neurological and developmental findings were common: 20.0% had developmental delay, 15.0% had seizures, and 10.0% had dysmorphic features. Asthma was more common in PIK3CD compared with PIK3R1 patients (63.6% vs 14.3%). More subjects with PIK3CD had CD3 lymphopenia compared with the PIK3R1 cohort. Seven patients underwent hematopoietic stem cell transplantation. One patient died from infectious complications. Conclusions: This is the first cohort comparing clinical manifestations in PIK3CD and PIK3R1 patients from the USIDNET Registry. Similar frequencies of respiratory and herpesvirus infections, lymphadenopathy, and developmental delay were observed compared with previous cohort studies. However, a higher frequency of asthma and CD3 lymphopenia in the PIK3CD cohort compared with the PIK3R1 cohort was observed.
KW - Activated phosphoinositide 3-kinase δ syndrome
KW - Combined immunodeficiency
KW - Phosphoinositide 3-kinase δ
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U2 - 10.1016/j.jaip.2021.07.044
DO - 10.1016/j.jaip.2021.07.044
M3 - Article
C2 - 34352450
AN - SCOPUS:85112791619
SN - 2213-2198
VL - 9
SP - 4095
EP - 4102
JO - Journal of Allergy and Clinical Immunology: In Practice
JF - Journal of Allergy and Clinical Immunology: In Practice
IS - 11
ER -