Progress in treatment of activated phosphoinositide 3-kinase δ syndrome

Abstract

Abstract:

Phosphoinositide 3-kinase δ (PI3Kδ) activated phosphoinositide 3-kinase δ syndrome (APDS) was first reported in 2013. APDS is an autosomal dominant primary immunodeficiency disease (PID) caused by mutations in thePIK3CDgene orPIK3R1gene. The clinical manifestations of APDS are recurrent respiratory tract infection, non-neoplastic lymphoid hyperplasia, autoimmune diseases and lymphoma. In this paper, the treatment of APDS is introduced in detail. In addition to conventional treatment for immunodeficiency, treatment such as antimicrobial prophylaxis, immunoglobulin replacement therapy and hematopoietic stem cell transplantation were reviewed, and more specific mammalian target of rapamycin (mTOR) inhibitors and PI3Kδ inhibitors were also discussed.

Key words:PI3Kδ overactivation syndrome,Hematopoietic stem cell transplantation,mTOR inhibitor,PI3Kδ inhibitor

CLC Number:

WU Tao, LIU Wenhui. Progress in treatment of activated phosphoinositide 3-kinase δ syndrome[J]. Journal of Internal Medicine Concepts & Practice, 2024, 19(02): 140-143.

References24

[1]	Jamee M, Moniri S, Zaki-Dizaji M, et al. Clinical, immunological, and genetic features in patients with activated PI3Kδ syndrome (APDS)[J].Clin Rev Allergy Immunol,2020,59(3):323-333.
[2]	Fruman DA, Chiu H, Hopkins BD, et al. The PI3K pathway in human disease[J].Cell,2017,170(4):605-635. doi:S0092-8674(17)30865-6pmid:28802037
[3]	Bilanges B, Posor Y, Vanhaesebroeck B. PI3K isoforms in cell signalling and vesicle trafficking[J].Nat Rev Mol Cell Biol,2019,20(9):515-534.
[4]	Thouenon R, Moreno-Corona N, Poggi L, et al. Activated PI3 kinase delta syndrome[J].Front Pediatr,2021,9:652405.
[5]	Dornan GL, Siempelkamp BD, Jenkins ML, et al. Conformational disruption of PI3Kδ regulation by immunodeficiency mutations in PIK3CD and PIK3R1[J].Proc Natl Acad Sci U S A,2017,114(8):1982-1987.
[6]	Nunes-Santos CJ, Uzel G, Rosenzweig SD. PI3K pathway defects leading to immunodeficiency and immune dysregulation[J].J Allergy Clin Immunol,2019,143(5):1676-1687. doi:S0091-6749(19)30421-Xpmid:31060715
[7]	Brodsky NN, Lucas CL. Infections in activated PI3K delta syndrome (APDS)[J].Curr Opin Immunol,2021,72:146-157.
[8]	Coulter TI, Cant AJ. The treatment of activated PI3Kδ syndrome[J].Front Immunol,2018,9:2043.
[9]	Chiriaco M, Brigida I, Ariganello P, et al. The case of an APDS patient[J].Clin Immunol,2017,178:20-28.
[10]	Edgar JDM, Richter AG, Huissoon AP, et al. Prescribing immunoglobulin replacement therapy for patients with non-classical and secondary antibody deficiency[J].J Clin Immunol,2018,38(2):204-213.
[11]	Singh A, Joshi V, Jindal AK, et al. An updated review on activated PI3 kinase delta syndrome (APDS)[J].Genes Dis,2019,7(1):67-74.
[12]	Lougaris V, Cancrini C, Rivalta B, et al. Activated phosphoinositide 3-dinase delta syndrome (APDS)[J].Pediatr Allergy Immunol,2022,33 Suppl 27: 69-72.
[13]	Moriya K, Mitsui-Sekinaka K, Sekinaka Y, et al. Clinical practice guideline for activated phosphatidyl inositol 3-kinase-delta syndrome in Japan[J].Immunol Med,2023,46(4):153-157.
[14]	Durandy A, Kracker S. Increased activation of PI3 kinase-δ predisposes to B-cell lymphoma[J].Blood,2020,135(9):638-643. doi:10.1182/blood.2019002072pmid:31942637
[15]	Yang X, Xi R, Bai J, et al. Successful haploidentical hematopoietic stem cell transplantation for activated phosphoinositide 3-kinase δ syndrome[J].Medicine (Baltimore),2023,102(5):e32816.
[16]	Dimitrova D, Nademi Z, Maccari ME, et al. International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome[J].J Allergy Clin Immunol,2022,149(1):410-421.
[17]	Nademi Z, Slatter MA, Dvorak CC, et al. Hematopoietic stem cell transplant in patients with activated PI3K delta syndrome[J].J Allergy Clin Immunol,2017,139(3):1046-1049. doi:S0091-6749(16)31288-Xpmid:27847301
[18]	Okano T, Imai K, Tsujita Y, et al. Hematopoietic stem cell transplantation for progressive combined immunodeficiency and lymphoproliferation in patients with activated phosphatidylinositol-3-OH kinase delta syndrome type 1[J].J Allergy Clin Immunol,2019,143(1):266-275.
[19]	Jung S, Gámez-Díaz L, Proietti M, et al. “Immune TOR-opathies,” a novel disease entity in clinical immunology[J].Front Immunol,2018,9:966.
[20]	Vanselow S, Wahn V, Schuetz C. Activated PI3Kδ syndrome - reviewing challenges in diagnosis and treatment[J].Front Immunol,2023,14:1208567.
[21]	Maccari ME, Abolhassani H, Aghamohammadi A, et al. Disease evolution and response to rapamycin in activated phosphoinositide 3-kinase δ syndrome front immunol[J].Front Immunol,2018,9:543.
[22]	Rao VK, Webster S, Dalm VASH, et al. Effective “activated PI3Kδ syndrome”-targeted therapy with the PI3Kδ inhibitor leniolisib[J].Blood,2017,130(21):2307-2316.
[23]	Cahn A, Hamblin JN, Begg M, et al. Safety, pharmacokinetics and dose-response characteristics of GSK2269557, an inhaled PI3Kδ inhibitor under development for the treatment of COPD[J].Pulm Pharmacol Ther,2017,46:69-77.
[24]	Begg M, Amour A, Jarvis E, et al. An open label trial of nemiralisib, an inhaled PI3 kinase delta inhibitor for the treatment of activated PI3 kinase delta syndrome[J].Pulm Pharmacol Ther,2023,79:102201.

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