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Clinical Reviews in Allergy & Immunology

Erschienen in:

01.04.2014

New Genetic Discoveries and Primary Immune Deficiencies

verfasst von: Vivian Hernandez-Trujillo

Erschienen in: Clinical Reviews in Allergy & Immunology | Ausgabe 2/2014

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Abstract

The field of immunology has undergone recent discoveries of genetic causes for many primary immunodeficiency diseases (PIDD). The ever-expanding knowledge has led to increased understanding behind the pathophysiology of these diseases. Since these diseases are rare, the patients are frequently misdiagnosed early in the presentation of their illnesses. The identification of new genes has increased our opportunities for recognizing and making the diagnosis in patients with PIDD before they succumb to infections that may result secondary to their PIDD. Some mutations lead to a variety of presentations of severe combined immunodeficiency (SCID). The myriad and ever-growing genetic mutations which lead to SCID phenotypes have been identified in recent years. Other mutations associated with some genetic syndromes have associated immunodeficiency and are important for making the diagnosis of primary immunodeficiency in patients with some syndromes, who may otherwise be missed within the larger context of their syndromes. A variety of mutations also lead to increased susceptibility to infections due to particular organisms. These patterns of infections due to specific organisms are important keys in properly identifying the part of the immune system which is affected in these patients. This review will discuss recent genetic discoveries that enhance our understanding of these complex diseases.

Al-Herz W, Bousfiha A, Casanova JL et al (2011) Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency. Front Immun 2:1–26CrossRef

Cossu F (2010) Genetics of SCID. Ital J Pediatr 36:76–93PubMedCentralPubMedCrossRef

De Saint BG, Geissmann F, Flori E et al (2004) Severe combined immunodeficiency caused by deficiency in either the δ or the ε subunit of CD3. J Clin Invest 114:1512–1517CrossRef

Dadi HK, Simon AJ, Roifman CM (2003) Effect of CD3 delta deficiency on maturation of alpha/beta and gamma/delta T cell lineages in severe combined immunodeficiency. N Engl J Med 349:1821–1828PubMedCrossRef

Gil J, Busto EM, Garcillan B et al (2011) A leaky mutation in CD3D differentially affects αβ and γδ T cells and leads to a Tαβ-Tγδ + B + NK + human SCID. J Clin Invest 121:3872–3876PubMedCentralPubMedCrossRef

Siegers GM, Swamy M, Fernandez-Malave E et al (2007 Oct 29) Different composition of the human and the mouse gamma delta T cell receptor explains different phenotypes of CD3 gamma and CD3 delta immunodeficiencies. J Exp Med 204(11):2537–2544

Rieux-Laucat F, Hivroz C, Lim A et al (2006) Inherited and somatic CD3 zeta mutations in a patient with T-cell deficiency. N Engl J Med 354:1913–1921PubMedCrossRef

Roberts JL, Lauritsen JP, Cooney M et al (2007) T-B + NK + severe combined immunodeficiency caused by complete deficiency of the CD3 zeta subunit of the T-cell antigen receptor complex. Blood 109(8):3198–3206PubMedCentralPubMedCrossRef

Kalman L, Lindegren ML, Kobrynski L et al (2004) Mutations in genes required for T-cell development: IL7R, CD45, IL2RG, JAK3, RAG1, RAG2, ARTEMIS and ADA and severe combined immunodeficiency: HuGE review. Genet Med 6:16–26PubMedCrossRef

10.

Tchilian EZ, Wallace DL, Wells RS et al (2001) A deletion in the gene encoding the CD45 antigen in a patient with SCID. J Immunol 166:1308–1313PubMed

11.

Kung C, Pingel JT, Heikinheimo M et al (2000) Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease. Nat Med 6:343–345PubMedCrossRef

12.

Roberts JL, Buckley RH, Luo B et al (2012) CD45-deficient severe combined immunodeficiency caused by uniparental disomy. Proc Natl Acad Sci USA 109:10456–10461PubMedCentralPubMedCrossRef

13.

Shiow LR, Roadcap DW, Paris K et al (2008) The actin regulator coronin-1A is mutated in a thymic egress deficient mouse strain and in a T-B + NK + SCID patient. Nat Immunol 9:1307–1315PubMedCentralPubMedCrossRef

14.

Goldman FD, Ballas ZK, Schutte BC et al (1998) Defective expression of p56lck in an infant with severe combined immunodeficiency. J Clin Invest 102:421–429PubMedCentralPubMedCrossRef

15.

Hauck F, Randriamampita C, Martin E et al (2012) Primary T-cell immunodeficiency with immunodysregulation caused by autosomal recessive LCK deficiency. J Allergy Clin Immunol 130:1144–1152PubMedCrossRef

16.

Hubert P, Bergeron F, Ferreira V et al (2000) Defective p56Lck activity in T cells from an adult patient with idiopathic CD4+ lymphocytopenia. Int Immunol 12:449–457PubMedCrossRef

17.

Pignata C, Fiore M, Guzzetta V et al (1996) Congenital alopecia and nail dystrophy associated with severe functional T-cell immunodeficiency in two sibs. Am J Med Genet 65:167–170PubMedCrossRef

18.

Adriani M, Martinez-Mir A, Fusco F et al (2004) Ancestral founder mutation of the nude (FOXN1) gene in congenital severe combined immunodeficiency associated with alopecia in southern Italy population. Ann Hum Genet 68:265–268PubMedCrossRef

19.

Amorosi S, D’Armiento M, Calcagno G et al (2008) FOXN1 homozygous mutation associated with anencephaly and severe neural tube defect in human athymic Nude/SCID fetus. Clin Genet 73:380–384PubMedCrossRef

20.

van der Burg M, Ijspeert H, Verkaik N et al (2009) A DNA-PKcs mutation in a radiosensitive T-B-SCID patient inhibits Artemis activation and nonhomologous end-joining. J Clin Invest 119:91–98PubMedCentralPubMed

21.

van der Burg M, van Dongen JJ, van Gent DC (2009) DNA-PKcs deficiency in human: long predicted, finally found. Curr Opin Allergy Clin Immunol 9:503–509PubMedCrossRef

22.

Dvorak CC, Cowan MJ (2010) Radiosensitive severe combined immunodeficiency disease. Immunol Allergy Clin N Am 30:125–141CrossRef

23.

Van der Burg M, van Veelen LR, Verkalk NS et al (2006) A new type of radiosensitive T−B−NK+ severe combined immunodeficiency caused by a LIG4 mutation. J Clin Invest 116:137–145PubMedCentralPubMedCrossRef

24.

Enders A, Fisch P, Schwarz K et al (2006) A severe form of human combined immunodeficiency due to mutations in DNA ligase IV. J Immunol 176:5060–5068PubMed

25.

Buck D, Malivert E, de Chasseval R, et al. (2006) Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly. Cell 124:287–299.

26.

Turul T, Tezcan I, Sanal O (2011) Cernunnos deficiency: a case report. J Investig Allergol Clin Immunol 21:313–316PubMed

27.

Pannicke U, Honig M, Hess I et al (2009) Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2. Nat Genet 41:101–105PubMedCrossRef

28.

Turul T, Tezcan I, Artac H et al (2009) Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency. Eur J Pediatr 168:87–93PubMedCrossRef

29.

Ouederni M, Vincent QB, Frange P et al (2011) Major histocompatability complex class II expression deficiency caused by a RFXANK founder mutation: a survey of 35 patients. Blood 118:5108–5118PubMedCrossRef

30.

Feske S, Picard C, Fischer A (2010) Immunodeficiency due to mutations in ORAI1 and STIM1. Clin Immunol 135:169–182PubMedCentralPubMedCrossRef

31.

Schuetz C, Huck K, Gudowius S et al (2008) An immunodeficiency disease with RAG mutations and granulomas. N Engl J Med 358:2030–2038PubMedCrossRef

32.

Heimall J, Keller M, Saltman R et al (2012) Diagnosis of 22q11.2 deletion syndrome and artemis deficiency in two children with T−B−NK+ immunodeficiency. J Clin Immunol 32:1141–1144PubMedCrossRef

33.

Stepensky P, Weintraub M, Yanir A et al (2011) IL2-inducible T-cell kinase deficiency: clinical presentation and therapeutic approach. Haematologica 96:472–476PubMedCentralPubMedCrossRef

34.

Huck K, Feyen O, Niehues T et al (2009) Girls homozygous for an IL-2 inducible T cell kinase mutation that leads to protein deficiency develop fatal EBV-associated lymphoproliferation. J Clin Invest 119:1350–1358PubMedCentralPubMedCrossRef

35.

Li FY, Chaigne-Delalande B, Kanellopoulou C et al (2012) Signaling role for Mg²⁺ revealed by immunodeficiency due to loss of Mag T1. Nature 475:471–476CrossRef

36.

Hale JE, Bonilla FA, Pai SY et al (2010) Identification of an infant with severe combined immunodeficiency by newborn screening. J Allergy Clin Immunol 126:1073–1074PubMedCrossRef

37.

Verbsky J, Thakar M, Routes J (2012) The Wisconsin approach to newborn screening for severe combined immunodeficiency. J Allergy Clin Immunol 129:622–627PubMedCrossRef

38.

Puck JM (2011) The case for newborn screening for severe combined immunodeficiency and related disorders. Ann NY Acad Sci 124:108–117CrossRef

39.

Roifman CM, Somech R, Kavadas F et al (2012) Defining combined immunodeficiency. J Allergy Clin Immunol 130:177–183PubMedCrossRef

40.

Cole TS, Cant AJ (2010) Clinical experience in T cell deficient patients. Allergy Asthma Clin Immunol 6:9–19PubMedCentralPubMedCrossRef

41.

Jyonouchi S, McDonald-McGinn DM, Bale S et al (2009) CHARGE (Coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness) syndrome and chromosome 22q11.2 deletion syndrome. A comparison of immunologic and nonimmunologic phenotypic features. Pediatrics 123:e871–e877PubMedCrossRef

42.

Grimbacher B, Holland SM, Gallin JI et al (1999) Hyper-IgE syndrome with recurrent infections—an autosomal dominant multisystem disorder. N Engl J Med 340:692–702PubMedCrossRef

43.

Holland SM, DeLeo FR, Elloumi HZ et al (2007) STAT3 mutations in the hyper-IgE syndrome. N Engl J Med 357:1608–1619PubMedCrossRef

44.

Milner JD, Brenchley JM, Laurence A et al (2008) Impaired TH 17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452:773–776PubMedCentralPubMedCrossRef

45.

Ma CS, Chew GYJ, Simpson N et al (2008) Deficiency of TH 17 cells in hyper IgE syndrome due to mutations in STAT3. J Exp Med 205:1551–1557PubMedCentralPubMedCrossRef

46.

Engelhardt KR, McGhee S, Winkler S et al (2009) Large deletions and point mutations involving DOCK8 in the autosomal recessive form of the hyper-IgE Syndrome. J Allergy Clin Immunol 124:1289–1300PubMedCentralPubMedCrossRef

47.

Su HC (2012) DOCK8 (dedicator of cytokinesis 8) deficiency. Curr Opin Allergy Clin Immunol 10:515–520CrossRef

48.

Zhang Q, Su HC (2011) Hyperimmunoglobulin E syndromes in pediatrics. Curr Opin Pediatr 23:653–658PubMedCentralPubMedCrossRef

49.

Minegishi Y, Karasuyama H (2009 Feb) Defects in Jak-STAT-mediated cytokine signals cause hyper-IgE syndrome: lessons from a primary immunodeficiency. Int Immunol 21(2):105–112

50.

Woellner C, Schaffer A, Puck JM et al (2007) The hyper IgE syndrome with mutations in TYK2. Immunity 26:535PubMedCrossRef

51.

Casey JP, Nobbs M, McGettigan P et al (2012) Recessive mutations in MCM4/PRKDC cause a novel syndrome involving a primary immunodeficiency and disorder of DNA repair. J Med Genet 49:242–245PubMedCrossRef

52.

Van Montfrans JM, Hoepelman AI, Otto S et al (2012) CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia. J Allergy Clin Immunol 129:787–793PubMedCentralPubMedCrossRef

53.

Tassone L, Notorangelo LD, Bonomi V et al (2009) Clinical and genetic diagnosis of warts, hypogammaglobulinemia, infections andmyelokathesis syndrome in 10 patients. J Allergy Clin Immunol 123:1170–1173PubMedCrossRef

54.

Bigley V, Collin M (2011 Aug) Dendritic cell, monocyte, B and NK lymphoid deficiency defines the lost lineages of a new GATA-2 dependent myelodysplastic syndrome. Haematologica 96:1081–1083

55.

Hambleton S, Salem S, Bustamante J et al (2011) Mutations in IRF8 and human dendritic cell immunodeficiency. N Engl J Med 365:127–138PubMedCentralPubMedCrossRef

56.

Van de Veerdonk FL, Plantinga TS, Hoischen A et al (2011) STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis. N Engl J Med 365:54–61PubMedCrossRef

57.

Liu L, Okada S, Kong XF et al (2011) Gain-of-functon human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J Exp Med 208:1635–1648PubMedCentralPubMedCrossRef

58.

Puel A, Cypowyj S, Buatamante J et al (2011) Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science 332:65–68PubMedCentralPubMedCrossRef

59.

Puel A, Doffinger R, Natividad A et al (2010) Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J Exp Med 207:291–297PubMedCentralPubMedCrossRef

60.

Hanna S, Etzioni A (2011) New host defense mechanisms against Candida species clarify the basis of clinical phenotypes. J Allergy Clin Immunol 127:1433–1437PubMedCrossRef

61.

Nahsen A, Dadi H, Bates A (2011) The L412F variant of Toll-like receptor 3 (TLR3) is associated with cutaneous candidiasis, increased susceptibility to cytomegalovirus, and autoimmunity. J Allergy Clin Immunol 127:528–531CrossRef

62.

Casrouge A, Zhang SY, Eidenschenk C et al (2006 Oct) Herpes simplex virus encephalitis in human UNC-93B deficiency. Science 314:308–312

63.

Pérez de Diego R, Sancho-Shimizu V et al (2010) Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like receptor 3 response and susceptibility to herpes simplex encephalitis. Immunity 33:400–411PubMedCrossRef

64.

Picard C, Casanova JL, Puel A (2011) Infectious diseases in patients with IRAK-4, MyD88, NEMO or Iκβα deficiency. Clin Microbiol Rev 24:490–497PubMedCentralPubMedCrossRef

Titel: New Genetic Discoveries and Primary Immune Deficiencies
verfasst von: Vivian Hernandez-Trujillo
Publikationsdatum: 01.04.2014
Verlag: Springer US
Erschienen in: Clinical Reviews in Allergy & Immunology / Ausgabe 2/2014
Print ISSN: 1080-0549
Elektronische ISSN: 1559-0267
DOI: https://doi.org/10.1007/s12016-013-8380-0

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