The First Iranian Cohort of Pediatric Patients with Activated Phosphoinositide 3-Kinase-δ (PI3Kδ) Syndrome (APDS)

Fekrvand, Saba; Delavari, Samaneh; Chavoshzadeh, Zahra; Sherkat, Roya; Mahdaviani, Seyed Alireza; Shabestari, Mahnaz Sadeghi; Azizi, Gholamreza; Arzanian, Mohammad Taghi; Shamsian, Bibi Shahin; Eskandarzadeh, Shabnam; Eslami, Neda; Rae, William; Condino‐Neto, Antônio; Mohammadi, Javad; Abolhassani, Hassan; Yazdani, Reza; Aghamohammadi, Asghar

doi:10.1080/08820139.2020.1863982

Cited by 7 publications

(11 citation statements)

References 46 publications

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“…Similar most common presentations (recurrent infection, lymphoproliferation, and autoimmunity) and immunoglobulins profiles (Hypogammaglobulinemia, Agammaglobulinemia, selective IgA deficiency, or hyper-IgM) were found in an Iranian Cohort of fifteen paediatric patients with APDS were studied and published in 2021. 33 As in our case, Autosomal dominant mutations within splice acceptor and donor sites of exon 11 of the PIK3R1 gene lead to APDS2. In a Cohort study done by Elodie Elkaim et al, records of 36 patients with genetically diagnosed APDS2 were collected and reviewed.…”

Section: Discussionsupporting

confidence: 62%

PIK3R1 mutation associated with primary immunodeficiency: a case of a 14-year-old male and review of the literature: case report

Alharbi¹,

Alzahrani²,

Afqi³

et al. 2023

JPNC

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We report a rare case of a 14-year-old boy diagnosed with Activated phosphoinositide 3-kinase delta syndrome Type 2 (APDS2). Based on a typical clinical presentation (Delayed teething, Prominent lymphadenopathy and recurrent characteristic infections started early in life and including multiple episodes of bilateral conjunctivitis, an extensive herpes skin infection in addition to recurrent upper sinopulmonary infections) along with suggestive laboratory immunological findings, and positive confirmatory genetic testing. After diagnosis, the patient was commenced on prophylactic antibiotics which resulted in a reduction in the frequency of his infections and hospitalizations. The targeted therapy of mTOR inhibition with Sirolimus and the possibility of hematopoietic stem cells transplantation are considered and discussed with the family, and he is on regular follow-up with the Allergy/Immunology team. APDS is a rare but increasingly reported inborn error of immunity. Gain-of-function and loss-of-function mutations in phosphoinositide 3-kinase (PIK3CD (encoding P 110 δ ) and PIK3R1 (encoding p 85 α , p 55 α , a n d p 50 α )) lead to APDS1 and APDS2, respectively. Our aim in reporting our case is to allow room for more elaboration of the different genotypes and clinical presentations of both types of APDS, in which early and accurate diagnosis will subsequently help in the initiation of outcome-improving therapy.

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Section: Discussionsupporting

confidence: 62%

PIK3R1 mutation associated with primary immunodeficiency: a case of a 14-year-old male and review of the literature: case report

Alharbi¹,

Alzahrani²,

Afqi³

et al. 2023

JPNC

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“…Notably, in APDS type 1, recurrent respiratory tract infections occur in nearly 98% of patients, followed by lymphoproliferation in 75%. Conversely, APDS type 2 is associated with upper respiratory tract infections in 100% of cases and lower respiratory tract infections in 77% [ 96 , 97 , 98 ]. Pathogens commonly implicated in APDS include Streptococcus pneumoniae , Haemophilus influenzae , Staphylococcus aureus , Moraxella catarrhalis , Pseudomonas aeruginosa , and the Klebsiella species, as well as viral infections such as Epstein–Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV), and varicella-zoster virus (VZV) [ 96 , 97 , 98 ].…”

Section: Activated Phosphoinositide 3-kinase δ Syndrome (Apds)mentioning

confidence: 99%

Infections in Disorders of Immune Regulation

Thangaraj,

Tyagi,

Suri

et al. 2024

Pathogens

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Primary immune regulatory disorders (PIRDs) constitute a spectrum of inborn errors of immunity (IEIs) that are primarily characterized by autoimmunity, lymphoproliferation, atopy, and malignancy. In PIRDs, infections are infrequent compared to other IEIs. While susceptibility to infection primarily stems from antibody deficiency, it is sometimes associated with additional innate immune and T or NK cell defects. The use of immunotherapy and chemotherapy further complicates the immune landscape, increasing the risk of diverse infections. Recurrent sinopulmonary infections, particularly bacterial infections such as those associated with staphylococcal and streptococcal organisms, are the most reported infectious manifestations. Predisposition to viral infections, especially Epstein–Barr virus (EBV)-inducing lymphoproliferation and malignancy, is also seen. Notably, mycobacterial and invasive fungal infections are rarely documented in these disorders. Knowledge about the spectrum of infections in these disorders would prevent diagnostic delays and prevent organ damage. This review delves into the infection profile specific to autoimmune lymphoproliferative syndrome (ALPS), Tregopathies, and syndromes with autoimmunity within the broader context of PIRD. Despite the critical importance of understanding the infectious aspects of these disorders, there remains a scarcity of comprehensive reports on this subject.

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“…Recurrent sinopulmonary tract infections are the most common clinical manifestation of APDS, affecting almost all patients described in the largest studies (3,(16)(17)(18)(19)(20)(21)(22) (see Table 1 for clinical features).…”

Section: Respiratory Tract Infectionsmentioning

confidence: 99%

“…Persistent local granulomatosis skin reactions to BCG vaccination have been described in 3 of 10 known BGC vaccinated patients with APDS1, and 2 of 18 BCG vaccinated patients with APDS2 ( 3 , 18 , 23 , 25 ). Recently, Fekrvand et al (2021) reported a patient with APDS2 who succumbed to a fatal BCG infection following BCG vaccination ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

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Disorders Related to PI3Kδ Hyperactivation: Characterizing the Clinical and Immunological Features of Activated PI3-Kinase Delta Syndromes

Redenbaugh

Coulter

2021

Front. Pediatr.

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Phosphoinositide-3-kinase δ (PI3Kδ) is found in immune cells and is part of the PI3K/AKT/mTOR/S6K signalling pathway essential to cell survival, growth and differentiation. Hyperactivation of PI3Kδ enzyme results in Activated PI3-kinase delta syndrome (APDS). This childhood onset, autosomal dominant, combined immunodeficiency, is caused by heterozygous gain of function (GOF) mutations in PIK3CD (encodes PI3Kδ catalytic subunit p110δ), mutations in PIK3R1 (encodes PI3Kδ regulatory subunit p85α) or LOF mutations in PTEN (terminates PI3Kδ signalling) leading to APDS1, APDS2 and APDS-Like (APDS-L), respectively. APDS was initially described in 2013 and over 285 cases have now been reported. Prompt diagnosis of APDS is beneficial as targeted pharmacological therapies such as sirolimus and potentially PI3Kδ inhibitors can be administered. In this review, we provide an update on the clinical and laboratory features of this primary immunodeficiency. We discuss the common manifestations such as sinopulmonary infections, bronchiectasis, lymphoproliferation, susceptibility to herpesvirus, malignancy, as well as more rare non-immune features such as short stature and neurodevelopmental abnormalities. Laboratory characteristics, such as antibody deficiency and B cell and T cell, phenotypes are also summarised.

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The First Iranian Cohort of Pediatric Patients with Activated Phosphoinositide 3-Kinase-δ (PI3Kδ) Syndrome (APDS)

Cited by 7 publications

References 46 publications

PIK3R1 mutation associated with primary immunodeficiency: a case of a 14-year-old male and review of the literature: case report

PIK3R1 mutation associated with primary immunodeficiency: a case of a 14-year-old male and review of the literature: case report

Infections in Disorders of Immune Regulation

Disorders Related to PI3Kδ Hyperactivation: Characterizing the Clinical and Immunological Features of Activated PI3-Kinase Delta Syndromes

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