Successful Sirolimus Treatment for Korean Patients with Activated Phosphoinositide 3-kinase δ Syndrome 1: the First Case Series in Korea

Kang, Jeung-Mo; Kim, Su Kyung; Kim, Dongsub; Choi, Sae Rom; Lim, Yeon Jung; Kim, Soon Ki; Park, Byung Kiu; Park, Weon Seo; Kang, Eun Suk; Ko, Young Hyeh; Choe, Yon Ho; Lee, Ji Won; Kim, Yae Jean

doi:10.3349/ymj.2020.61.6.542

Cited by 10 publications

(12 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These frequencies are consistent with previously reported studies (6). In our subjects, diarrhea was the most common symptom (13/19, 68.4%), followed by hematochezia, abdominal pain and growth impairment, which were previously reported as prevalent GI symptoms in IEI patients (7,9,(15)(16)(17)(18)(19)(20)(21)(22). It is already known that growth impairment was frequently detected, and the risk of growth failure is four times higher than in the healthy pediatric population (23)(24)(25).…”

Section: Discussionsupporting

confidence: 92%

Needs for Increased Awareness of Gastrointestinal Manifestations in Patients With Human Inborn Errors of Immunity

Kim

Yoon

et al. 2021

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

The gastrointestinal (GI) tract is frequently affected by inborn errors of immunity (IEI), and GI manifestations can be present in IEI patients before a diagnosis is confirmed. We aimed to investigate clinical features, endoscopic and histopathologic findings in IEI patients. This was a retrospective cohort study conducted from 1995 to 2020. Eligible patients were diagnosed with IEI and had GI manifestations that were enough to require endoscopies. IEI was classified according to the International Union of Immunological Societies classification. Of 165 patients with IEI, 55 (33.3%) had GI manifestations, and 19 (11.5%) underwent endoscopy. Among those 19 patients, nine (47.4%) initially presented with GI manifestations. Thirteen patients (68.4%) were male, and the mean age of patients 11.5 ± 7.9 years (range, 0.6 – 26.6) when they were consulted and evaluated with endoscopy. The most common type of IEI with severe GI symptoms was “Disease of immune dysregulation” (31.6%) followed by “Phagocyte defects” (26.3%), according to the International Union of Immunological Societies classification criteria. Patients had variable GI symptoms such as chronic diarrhea (68.4%), hematochezia (36.8%), abdominal pain (31.6%), perianal disease (10.5%), and recurrent oral ulcers (10.5%). During the follow-up period, three patients developed GI tract neoplasms (early gastric carcinoma, mucosa associated lymphoid tissue lymphoma of colon, and colonic tubular adenoma, 15.8%), and 12 patients (63.2%) were diagnosed with inflammatory bowel disease (IBD)-like colitis. Investigating immunodeficiency in patients with atypical GI symptoms can provide an opportunity for correct diagnosis and appropriate disease-specific therapy. Gastroenterologists and immunologists should consider endoscopy when atypical GI manifestations appear in IEI patients to determine if IBD-like colitis or neoplasms including premalignant and malignant lesions have developed. Also, if physicians in various fields are better educated about IEI-specific complications, early diagnosis and disease-specific treatment for IEI will be made possible.

show abstract

Section: Discussionsupporting

confidence: 92%

Needs for Increased Awareness of Gastrointestinal Manifestations in Patients With Human Inborn Errors of Immunity

Kim

Yoon

et al. 2021

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Extended lymphocyte phenotypes have shown: reduced naive CD4+ T cells (CD4+CD45RA+); increased activated CD8+ T cells (CD8+CD45RO+); reduced class-switched memory B cells and expanded transitional B cells (15). Kang et al reported impaired lymphocyte proliferation to PHA in 3/3 of their patients (24).…”

Section: Lymphocyte Studiesmentioning

confidence: 99%

“…Septicaemia, meningitis, infectious lymphadenitis, osteomyelitis, dental abscesses and Staphylococcus aureus skin abscesses are also described ( 15 , 16 , 19 , 24 ).…”

Section: Introductionmentioning

confidence: 99%

“…Benign lymphoproliferation is the second most common manifestation of APDS (after respiratory tract infections), present in the majority of patients (59–93%) ( 3 , 15 , 16 , 19 , 20 , 24 ). Lymphadenopathy occurs most frequently (61%), followed by splenomegaly (47%) and hepatomegaly (29%) ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

“…Neurodevelopmental delay may present as mild cognitive impairment or learning disabilities ( 21 ). Macrocrania has been described in APDS1 ( 3 , 24 ) and microcephaly in APDS2 ( 35 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Redenbaugh

Coulter

2021

Front. Pediatr.

View full text Add to dashboard Cite

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.

show abstract

Systematic review of mortality and survival rates for APDS

Hanson,

Bonnen

2024

Clin Exp Med

View full text Add to dashboard Cite

Activated phosphoinositide 3-kinase delta syndrome (APDS) is a rare genetic disorder that presents clinically as a primary immunodeficiency. Clinical presentation of APDS includes severe, recurrent infections, lymphoproliferation, lymphoma, and other cancers, autoimmunity and enteropathy. Autosomal dominant variants in two independent genes have been demonstrated to cause APDS. Pathogenic variants in PIK3CD and PIK3R1, both of which encode components of the PI3-kinase, have been identified in subjects with APDS. APDS1 is caused by gain of function variants in the PIK3CD gene, while loss of function variants in PIK3R1 have been reported to cause APDS2. We conducted a review of the medical literature and identified 256 individuals who had a molecular diagnosis for APDS as well as age at last report; 193 individuals with APDS1 and 63 with APDS2. Despite available treatments, survival for individuals with APDS appears to be shortened from the average lifespan. A Kaplan–Meier survival analysis for APDS showed the conditional survival rate at the age of 20 years was 87%, age of 30 years was 74%, and ages of 40 and 50 years were 68%. Review of causes of death showed that the most common cause of death was lymphoma, followed by complications from HSCT. The overall mortality rate for HSCT in APDS1 and APDS2 cases was 15.6%, while the mortality rate for lymphoma was 47.6%. This survival and mortality data illustrate that new treatments are needed to mitigate the risk of death from lymphoma and other cancers as well as infection. These analyses based on real-world evidence gathered from the medical literature comprise the largest study of survival and mortality for APDS to date.

show abstract

Successful Sirolimus Treatment for Korean Patients with Activated Phosphoinositide 3-kinase δ Syndrome 1: the First Case Series in Korea

Cited by 10 publications

References 12 publications

Needs for Increased Awareness of Gastrointestinal Manifestations in Patients With Human Inborn Errors of Immunity

Needs for Increased Awareness of Gastrointestinal Manifestations in Patients With Human Inborn Errors of Immunity

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

Systematic review of mortality and survival rates for APDS

Contact Info

Product

Resources

About