Activating PI3Kδ mutations in a cohort of 669 patients with primary immunodeficiency

Clinical and Experimental Immunology

Volumn 183, Issue 2, 2016, Pages 221-229

  Elgizouli, M ^a,c   Lowe, D M ^b   Speckmann, C ^a   Schubert, D ^a,c   Hulsdunker J ^a,c   Eskandarian, Z ^a   Dudek, A ^a,c   Schmitt Graeff, A ^a   Wanders, J ^b   Jorgensen S F ^d   Fevang, B ^d   Salzer, U ^a   Nieters, A ^a   Burns, S ^b   Grimbacher, B ^a,b  

^a UNIVERSITY OF FREIBURG   (Germany)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c UNIVERSITY OF FREIBURG   (Germany)

^d UNIVERSITY OF OSLO   (Norway)

Author keywords

B cells; Common variable immunodeficiency; Hypogammaglobulinaemia; PI3K ; Primary immunodeficiency

Indexed keywords

GRANULOCYTE COLONY STIMULATING FACTOR; IMMUNOGLOBULIN; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M; PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE 3 KINASE; PIK3CD PROTEIN, HUMAN;

ACTIVATED PHOSPHATIDYLINOSITOL 3 KINASE DELTA SYNDROME; ADOLESCENT; ADULT; ARTICLE; CASE REPORT; CHILD; COMBINED IMMUNODEFICIENCY; COMMON VARIABLE IMMUNODEFICIENCY; FEMALE; GAIN OF FUNCTION MUTATION; GENE; GENETIC DISORDER; GENETIC SCREENING; HUMAN; IMMUNE DEFICIENCY; IMMUNOGLOBULIN G DEFICIENCY; MALE; PHOSPHATIDYLINOSITOL 3 KINASE DELTA GENE; PRIORITY JOURNAL; PYROSEQUENCING; SCHOOL CHILD; SIBLING; YOUNG ADULT; AGAMMAGLOBULINEMIA; B LYMPHOCYTE; GENETICS; HIGH THROUGHPUT SEQUENCING; IMMUNOLOGY; IMMUNOPHENOTYPING; METABOLISM; MIDDLE AGED; MUTATION; T LYMPHOCYTE;

ADOLESCENT; ADULT; AGAMMAGLOBULINEMIA; B-LYMPHOCYTES; CHILD; CLASS I PHOSPHATIDYLINOSITOL 3-KINASES; COMMON VARIABLE IMMUNODEFICIENCY; FEMALE; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; IMMUNOLOGIC DEFICIENCY SYNDROMES; IMMUNOPHENOTYPING; MALE; MIDDLE AGED; MUTATION; SIBLINGS; T-LYMPHOCYTES; YOUNG ADULT;

EID: 84955199772     PISSN: 00099104     EISSN: 13652249     Source Type: Journal    
DOI: 10.1111/cei.12706     Document Type: Article

References (34)

1. Al-Herz W, Bousfiha A, Casanova JL et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency. Front Immunol 2014; 5:162.
2. Grimbacher B, Hutloff A, Schlesier M et al. Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat Immunol 2003; 4:261-8.
3. Vanhaesebroeck B, Welham MJ, Kotani K et al. P110delta, a novel phosphoinositide 3-kinase in leukocytes. Proc Natl Acad Sci USA 1997; 94:4330-5.
4. Kok K, Geering B, Vanhaesebroeck B. Regulation of phosphoinositide 3-kinase expression in health and disease. Trends Biochem Sci 2009; 34:115-27.
5. Okkenhaug K. Signaling by the phosphoinositide 3-kinase family in immune cells. Annu Rev Immunol 2013; 31:675-704.
6. Angulo I, Vadas O, Garcon F et al. Phosphoinositide 3-kinase delta gene mutation predisposes to respiratory infection and airway damage. Science 2013; 342:866-71.
7. Lucas CL, Kuehn HS, Zhao F et al. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110delta result in T cell senescence and human immunodeficiency. Nat Immunol 2014; 15:88-97.
8. Lucas CL, Zhang Y, Venida A et al. Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K. J Exp Med 2014; 211:2537-47.
9. Deau MC, Heurtier L, Frange P et al. A human immunodeficiency caused by mutations in the PIK3R1 gene. J Clin Invest 2014; 124:3923-8.
10. Yong PF, Thaventhiran JE, Grimbacher B. 'A rose is a rose is a rose, ' but CVID is not CVID common variable immune deficiency (CVID), what do we know in 2011? Adv Immunol 2011; 111:47-107.
11. Felgentreff K, Perez-Becker R, Speckmann C et al. Clinical and immunological manifestations of patients with atypical severe combined immunodeficiency. Clin Immunol 2011; 141:73-82.
12. Roifman CM, Somech R, Kavadas F et al. Defining combined immunodeficiency. J Allergy Clin Immunol 2012; 130:177-83.
13. van der Burg M, Gennery AR. Educational paper. The expanding clinical and immunological spectrum of severe combined immunodeficiency. Eur J Pediatr 2011; 170:561-71.
14. Conley ME, Dobbs AK, Farmer DM et al. Primary B cell immunodeficiencies: comparisons and contrasts. Annu Rev Immunol 2009; 27:199-227.
15. Bauer TM, Patel MR, Infante JR. Targeting PI3 kinase in cancer. Pharmacol Ther 2015; 146:53-60.
16. Chonmaitree T, Revai K, Grady JJ et al. Viral upper respiratory tract infection and otitis media complication in young children. Clin Infect Dis 2008; 46:815-23.
17. Kusel MM, de Klerk NH, Holt PG, Kebadze T, Johnston SL, Sly PD. Role of respiratory viruses in acute upper and lower respiratory tract illness in the first year of life: a birth cohort study. Pediatr Infect Dis J 2006; 25:680-6.
18. Kracker S, Curtis J, Ibrahim MA et al. Occurrence of B-cell lymphomas in patients with activated phosphoinositide 3-kinase delta syndrome. J Allergy Clin Immunol 2014; 134:233-6.
19. Crank MC, Grossman JK, Moir S et al. Mutations in PIK3CD can cause hyper-IgM syndrome (HIGM) associated with increased cancer susceptibility. J Clin Immunol 2014; 34:272-6.
20. Conley ME, Fruman DA. Genetics. Can cancer drugs treat immunodeficiency? Science 2013; 342:814-5.
21. Royo JL, Hidalgo M, Ruiz A. Pyrosequencing protocol using a universal biotinylated primer for mutation detection and SNP genotyping. Nat Protoc 2007; 2:1734-9.
22. Qamar N, Fuleihan RL. The hyper-IgM syndromes. Clin Rev Allergy Immunol 2014; 46:120-30.
23. Lopez-Herrera G, Tampella G, Pan-Hammarstrom Q et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet 2012; 90:986-1001.
24. Alangari A, Alsultan A, Adly N et al. LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency. J Allergy Clin Immunol 2012; 130:481-8.e2.
25. Huck K, Feyen O, Niehues T et al. Girls homozygous for an IL-2-inducible T cell kinase mutation that leads to protein deficiency develop fatal EBV-associated lymphoproliferation. J Clin Invest 2009; 119:1350-8.
26. Serwas NK, Cagdas D, Ban SA et al. Identification of ITK deficiency as a novel genetic cause of idiopathic CD4+ T-cell lymphopenia. Blood 2014; 124:655-7.
27. Bienemann K, Borkhardt A, Klapper W, Oschlies I. High incidence of Epstein-Barr virus (EBV)-positive Hodgkin lymphoma and Hodgkin lymphoma-like B-cell lymphoproliferations with EBV latency profile 2 in children with interleukin-2-inducible T-cell kinase deficiency. Histopathology 2015; 67:607-16.
28. van Montfrans JM, Hoepelman AI, Otto S et al. CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia. J Allergy Clin Immunol 2012; 129:787-93.e6.
29. Salzer E, Daschkey S, Choo S et al. Combined immunodeficiency with life-threatening EBV-associated lymphoproliferative disorder in patients lacking functional CD27. Haematologica 2013; 98:473-8.
30. Booth C, Gilmour KC, Veys P et al. X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease. Blood 2011; 117:53-62.
31. Cleland SY, Siegel RM. Wiskott-Aldrich Syndrome at the nexus of autoimmune and primary immunodeficiency diseases. FEBS Lett 2011; 585:3710-4.
32. Imai K, Morio T, Zhu Y et al. Clinical course of patients with WASP gene mutations. Blood 2004; 103:456-64.
33. Schubert D, Bode C, Kenefeck R et al. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat Med 2014; 20:1410-6.
34. Kuehn HS, Ouyang W, Lo B et al. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science 2014; 345:1623-7.