Clinical, Immunological, and Genetic Features in Patients with Activated PI3Kδ Syndrome (APDS): a Systematic Review

被引:90
作者
Jamee, Mahnaz [1 ,2 ]
Moniri, Shakiba [1 ,2 ]
Zaki-Dizaji, Majid [3 ,4 ]
Olbrich, Peter [5 ]
Yazdani, Reza [4 ]
Jadidi-Niaragh, Farhad [6 ,7 ]
Aghamahdi, Fatemeh [2 ,8 ]
Abolhassani, Hassan [9 ]
Condliffe, Alison M. [10 ]
Aghamohammadi, Asghar [4 ]
Azizi, Gholamreza [2 ]
机构
[1] Alborz Univ Med Sci, Student Res Comm, Karaj, Iran
[2] Alborz Univ Med Sci, Noncommunicable Dis Res Ctr, Karaj, Iran
[3] Legal Med Org, Legal Med Res Ctr, Tehran, Iran
[4] Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Childrens Med Ctr, Tehran, Iran
[5] Hosp Virgen Rocio, Inst Biomed Sevilla IBiS, Secc Infectol & Inmunopatol, Unidad Pediat, Seville, Spain
[6] Tabriz Univ Med Sci, Immunol Res Ctr, Tabriz, Iran
[7] Tabriz Univ Med Sci, Sch Med, Dept Immunol, Tabriz, Iran
[8] Alborz Univ Med Sci, Sch Med, Dept Pediat Endocrinol, Karaj, Iran
[9] Karolinska Inst, Karolinska Univ Hosp Huddinge, Dept Lab Med, Div Clin Immunol, Stockholm, Sweden
[10] Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England
关键词
APDS; Activated phosphoinositide 3-kinase δ syndrome; Phosphoinositide-3-kinase δ Hyper-IgM syndrome; 3-KINASE DELTA SYNDROME; EPSTEIN-BARR-VIRUS; GAIN-OF-FUNCTION; RECURRENT SINOPULMONARY INFECTIONS; HYPER IGM SYNDROME; PHOSPHATIDYLINOSITOL; 3-KINASE; HUMAN IMMUNODEFICIENCY; HIGH-FREQUENCY; B-CELLS; MUTATIONS;
D O I
10.1007/s12016-019-08738-9
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Activated phosphoinositide 3-kinase delta syndrome (APDS) is a novel primary immunodeficiency (PID) caused by heterozygous gain of function mutations in PI3K delta catalytic p110 delta (PIK3CD) or regulatory p85 alpha (PIK3R1) subunits leading to APDS1 and APDS2, respectively. Patients with APDS present a spectrum of clinical manifestations, particularly recurrent respiratory infections and lymphoproliferation. We searched PubMed, Web of Science, and Scopus databases for APDS patients and screened for eligibility criteria. A total of 243 APDS patients were identified from 55 articles. For all patients, demographic, clinical, immunologic, and molecular data were collected. Overall, 179 APDS1 and 64 APDS2 patients were identified. The most common clinical manifestations were respiratory tract infections (pneumonia (43.6%), otitis media (28.8%), and sinusitis (25.9%)), lymphoproliferation (70.4%), autoimmunity (28%), enteropathy (26.7%), failure to thrive (20.6%), and malignancy (12.8%). The predominant immunologic phenotype was hyper-IgM syndrome (48.1%). Immunologic profiling showed decreased B cells in 74.8% and CD4(+) T cells in 64.8% of APDS patients. The c.3061 G>A (p. E1021K) mutation in APDS1 with 85% frequency and c.1425+1 G> (A, C, T) (p.434-475del) mutation in APDS2 with 79% frequency were hotspot mutations. The majority of APDS patients were placed on long-term immunoglobulin replacement therapy. Immunosuppressive agents such as rituximab, tacrolimus, rapamycin, and leniolisib were also administered for autoimmunity and inflammatory complications. In addition, hematopoietic stem cell transplantation (HSCT) was used in 12.8% of patients. APDS has heterogynous clinical manifestations. It should be suspected in patients with history of recurrent respiratory infections, lymphoproliferation, and raised IgM levels. Moreover, HSCT should be considered in patients with severe and complicated clinical manifestations with no or insufficient response to the conventional therapies.
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收藏
页码:323 / 333
页数:11
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