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Abstract

Primary atopic disorders describes a series of monogenic diseases that have allergy- or atopic effector–related symptoms as a substantial feature. The underlying pathogenic genetic lesions help illustrate fundamental pathways in atopy, opening up diagnostic and therapeutic options for further study in those patients, but ultimately for common allergic diseases as well. Key pathways affected in these disorders include T cell receptor and B cell receptor signaling, cytokine signaling, skin barrier function, and mast cell function, as well as pathways that have not yet been elucidated. While comorbidities such as classically syndromic presentation or immune deficiency are often present, in some cases allergy alone is the presenting symptom, suggesting that commonly encountered allergic diseases exist on a spectrum of monogenic and complex genetic etiologies that are impacted by environmental risk factors.

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2020-04-26
2024-06-14
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Literature Cited

  1. 1. 
    Bonnelykke K, Sparks R, Waage J, Milner JD 2015. Genetics of allergy and allergic sensitization: common variants, rare mutations. Curr. Opin. Immunol. 36:115–26
    [Google Scholar]
  2. 2. 
    Lyons JJ, Milner JD. 2018. Primary atopic disorders. J. Exp. Med. 215:1009–22
    [Google Scholar]
  3. 3. 
    Sacco KA, Milner JD. 2019. Gene-environment interactions in primary atopic disorders. Curr. Opin. Immunol. 60:148–55
    [Google Scholar]
  4. 4. 
    Sokol K, Milner JD. 2018. The overlap between allergy and immunodeficiency. Curr. Opin. Pediatr. 30:848–54
    [Google Scholar]
  5. 5. 
    Villa A, Notarangelo LD, Roifman CM 2008. Omenn syndrome: inflammation in leaky severe combined immunodeficiency. J. Allergy Clin. Immunol. 122:1082–86
    [Google Scholar]
  6. 6. 
    Joshi AY, Ham EK, Shah NB, Dong X, Khan SP, Abraham RS 2012. Atypical Omenn syndrome due to adenosine deaminase deficiency. Case Rep. Immunol. 2012:919241
    [Google Scholar]
  7. 7. 
    Turul T, Tezcan I, Artac H, de Bruin-Versteeg S, Barendregt BH et al. 2009. Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency. Eur. J. Pediatr. 168:87–93
    [Google Scholar]
  8. 8. 
    Markert ML, Alexieff MJ, Li J, Sarzotti M, Ozaki DA et al. 2004. Complete DiGeorge syndrome: development of rash, lymphadenopathy, and oligoclonal T cells in 5 cases. J. Allergy Clin. Immunol. 113:734–41
    [Google Scholar]
  9. 9. 
    Milner JD, Ward JM, Keane-Myers A, Paul WE 2007. Lymphopenic mice reconstituted with limited repertoire T cells develop severe, multiorgan, Th2-associated inflammatory disease. PNAS 104:576–81
    [Google Scholar]
  10. 10. 
    Haribhai D, Williams JB, Jia S, Nickerson D, Schmitt EG et al. 2011. A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity. Immunity 35:109–22
    [Google Scholar]
  11. 11. 
    Lawrence MG, Barber JS, Sokolic RA, Garabedian EK, Desai AN et al. 2013. Elevated IgE and atopy in patients treated for early-onset ADA-SCID. J. Allergy Clin. Immunol. 132:1444–46
    [Google Scholar]
  12. 12. 
    Cavadini P, Vermi W, Facchetti F, Fontana S, Nagafuchi S et al. 2005. AIRE deficiency in thymus of 2 patients with Omenn syndrome. J. Clin. Investig. 115:728–32
    [Google Scholar]
  13. 13. 
    Milner JD, Fazilleau N, McHeyzer-Williams M, Paul W 2010. Cutting edge: lack of high affinity competition for peptide in polyclonal CD4+ responses unmasks IL-4 production. J. Immunol. 184:6569–73
    [Google Scholar]
  14. 14. 
    Constant SL, Bottomly K. 1997. Induction of Th1 and Th2 CD4+ T cell responses: the alternative approaches. Annu. Rev. Immunol. 15:297–322
    [Google Scholar]
  15. 15. 
    Yamane H, Paul WE. 2013. Early signaling events that underlie fate decisions of naive CD4+ T cells toward distinct T-helper cell subsets. Immunol. Rev. 252:12–23
    [Google Scholar]
  16. 16. 
    Hosken NA, Shibuya K, Heath AW, Murphy KM, O'Garra A 1995. The effect of antigen dose on CD4+ T helper cell phenotype development in a T cell receptor–αβ–transgenic model. J. Exp. Med. 182:1579–84
    [Google Scholar]
  17. 17. 
    Tao X, Grant C, Constant S, Bottomly K 1997. Induction of IL-4-producing CD4+ T cells by antigenic peptides altered for TCR binding. J. Immunol. 158:4237–44
    [Google Scholar]
  18. 18. 
    Jorritsma PJ, Brogdon JL, Bottomly K 2003. Role of TCR-induced extracellular signal-regulated kinase activation in the regulation of early IL-4 expression in naive CD4+ T cells. J. Immunol. 170:2427–34
    [Google Scholar]
  19. 19. 
    Barber JS, Yokomizo LK, Sheikh V, Freeman AF, Garabedian E et al. 2013. Peptide library-based evaluation of T-cell receptor breadth detects defects in global and regulatory activation in human immunologic diseases. PNAS 110:8164–69
    [Google Scholar]
  20. 20. 
    van Panhuys N, Klauschen F, Germain RN 2014. T-cell-receptor-dependent signal intensity dominantly controls CD4+ T cell polarization in vivo. Immunity 41:63–74
    [Google Scholar]
  21. 21. 
    Jakob T, Kollisch GV, Howaldt M, Bewersdorff M, Rathkolb B et al. 2008. Novel mouse mutants with primary cellular immunodeficiencies generated by genome-wide mutagenesis. J. Allergy Clin. Immunol. 121:179–84.e7
    [Google Scholar]
  22. 22. 
    Mingueneau M, Roncagalli R, Gregoire C, Kissenpfennig A, Miazek A et al. 2009. Loss of the LAT adaptor converts antigen-responsive T cells into pathogenic effectors that function independently of the T cell receptor. Immunity 31:197–208
    [Google Scholar]
  23. 23. 
    Jun JE, Wilson LE, Vinuesa CG, Lesage S, Blery M et al. 2003. Identifying the MAGUK protein Carma-1 as a central regulator of humoral immune responses and atopy by genome-wide mouse mutagenesis. Immunity 18:751–62
    [Google Scholar]
  24. 24. 
    Policheni A, Horikawa K, Milla L, Kofler J, Bouillet P et al. 2019. CARD11 is dispensable for homeostatic responses and suppressive activity of peripherally induced FOXP3+ regulatory T cells. Immunol. Cell Biol. 97:740–52
    [Google Scholar]
  25. 25. 
    Bertin J, Wang L, Guo Y, Jacobson MD, Poyet JL et al. 2001. CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-κB. J. Biol. Chem. 276:11877–82
    [Google Scholar]
  26. 26. 
    Hamilton KS, Phong B, Corey C, Cheng J, Gorentla B et al. 2014. T cell receptor-dependent activation of mTOR signaling in T cells is mediated by Carma1 and MALT1, but not Bcl10. Sci. Signal. 7:ra55
    [Google Scholar]
  27. 27. 
    Greil J, Rausch T, Giese T, Bandapalli OR, Daniel V et al. 2013. Whole-exome sequencing links caspase recruitment domain 11 (CARD11) inactivation to severe combined immunodeficiency. J. Allergy Clin. Immunol. 131:1376–83.e3
    [Google Scholar]
  28. 28. 
    Stepensky P, Keller B, Buchta M, Kienzler AK, Elpeleg O et al. 2013. Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects. J. Allergy Clin. Immunol. 131:477–85.e1
    [Google Scholar]
  29. 29. 
    Jabara HH, Ohsumi T, Chou J, Massaad MJ, Benson H et al. 2013. A homozygous mucosa-associated lymphoid tissue 1 (MALT1) mutation in a family with combined immunodeficiency. J. Allergy Clin. Immunol. 132:151–58
    [Google Scholar]
  30. 30. 
    Punwani D, Wang H, Chan AY, Cowan MJ, Mallott J et al. 2015. Combined immunodeficiency due to MALT1 mutations, treated by hematopoietic cell transplantation. J. Clin. Immunol. 35:135–46
    [Google Scholar]
  31. 31. 
    Torres JM, Martinez-Barricarte R, Garcia-Gomez S, Mazariegos MS, Itan Y et al. 2014. Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity. J. Clin. Investig. 124:5239–48
    [Google Scholar]
  32. 32. 
    Frizinsky S, Rechavi E, Barel O, Najeeb RH, Greenberger S et al. 2019. Novel MALT1 mutation linked to immunodeficiency, immune dysregulation, and an abnormal T cell receptor repertoire. J. Clin. Immunol. 39:401–13
    [Google Scholar]
  33. 33. 
    Somech R, Lev A, Lee YN, Simon AJ, Barel O et al. 2017. Disruption of thrombocyte and T lymphocyte development by a mutation in ARPC1B.J. . Immunol 199:4036–45
    [Google Scholar]
  34. 34. 
    Dadi H, Jones TA, Merico D, Sharfe N, Ovadia A et al. 2017. Combined immunodeficiency and atopy caused by a dominant negative mutation in caspase activation and recruitment domain family member 11 (CARD11). J. Allergy Clin. Immunol. 141:1818–30.e2
    [Google Scholar]
  35. 35. 
    Altin JA, Tian L, Liston A, Bertram EM, Goodnow CC, Cook MC 2011. Decreased T-cell receptor signaling through CARD11 differentially compromises forkhead box protein 3-positive regulatory versus TH2 effector cells to cause allergy. J. Allergy Clin. Immunol. 127:1277–85.e5
    [Google Scholar]
  36. 36. 
    Barnes MJ, Krebs P, Harris N, Eidenschenk C, Gonzalez-Quintial R et al. 2009. Commitment to the regulatory T cell lineage requires CARMA1 in the thymus but not in the periphery. PLOS Biol 7:e51
    [Google Scholar]
  37. 37. 
    Bornancin F, Renner F, Touil R, Sic H, Kolb Y et al. 2015. Deficiency of MALT1 paracaspase activity results in unbalanced regulatory and effector T and B cell responses leading to multiorgan inflammation. J. Immunol. 194:3723–34
    [Google Scholar]
  38. 38. 
    Brustle A, Brenner D, Knobbe-Thomsen CB, Cox M, Lang PA et al. 2017. MALT1 is an intrinsic regulator of regulatory T cells. Cell Death Differ 24:1214–23
    [Google Scholar]
  39. 39. 
    Di Pilato M, Kim EY, Cadilha BL, Prussmann JN, Nasrallah MN et al. 2019. Targeting the CBM complex causes Treg cells to prime tumours for immune checkpoint therapy. Nature 570:112–16
    [Google Scholar]
  40. 40. 
    Medoff BD, Sandall BP, Landry A, Nagahama K, Mizoguchi A et al. 2009. Differential requirement for CARMA1 in agonist-selected T-cell development. Eur. J. Immunol. 39:78–84
    [Google Scholar]
  41. 41. 
    Molinero LL, Yang J, Gajewski T, Abraham C, Farrar MA, Alegre ML 2009. CARMA1 controls an early checkpoint in the thymic development of FoxP3+ regulatory T cells. J. Immunol. 182:6736–43
    [Google Scholar]
  42. 42. 
    Schmidt-Supprian M, Tian J, Grant EP, Pasparakis M, Maehr R et al. 2004. Differential dependence of CD4+CD25+ regulatory and natural killer-like T cells on signals leading to NF-κB activation. PNAS 101:4566–71
    [Google Scholar]
  43. 43. 
    Rosenbaum M, Gewies A, Pechloff K, Heuser C, Engleitner T et al. 2019. Bcl10-controlled Malt1 paracaspase activity is key for the immune suppressive function of regulatory T cells. Nat. Commun. 10:2352
    [Google Scholar]
  44. 44. 
    Nakaya M, Xiao Y, Zhou X, Chang JH, Chang M et al. 2014. Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation. Immunity 40:692–705
    [Google Scholar]
  45. 45. 
    Delgoffe GM, Pollizzi KN, Waickman AT, Heikamp E, Meyers DJ et al. 2011. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat. Immunol. 12:295–303
    [Google Scholar]
  46. 46. 
    Klysz D, Tai X, Robert PA, Craveiro M, Cretenet G et al. 2015. Glutamine-dependent α-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation. Sci. Signal. 8:ra97
    [Google Scholar]
  47. 47. 
    Liu Y, Wang Z, De La Torre R, Barling A, Tsujikawa T et al. 2017. Trim32 deficiency enhances Th2 immunity and predisposes to features of atopic dermatitis. J. Investig. Dermatol. 137:359–66
    [Google Scholar]
  48. 48. 
    Mark BJ, Becker BA, Halloran DR, Bree AF, Sindwani R et al. 2012. Prevalence of atopic disorders and immunodeficiency in patients with ectodermal dysplasia syndromes. Ann. Allergy Asthma Immunol. 108:435–38
    [Google Scholar]
  49. 49. 
    Tuano KS, Orange JS, Sullivan K, Cunningham-Rundles C, Bonilla FA, Davis CM 2015. Food allergy in patients with primary immunodeficiency diseases: prevalence within the US Immunodeficiency Network (USIDNET). J. Allergy Clin. Immunol. 135:273–75
    [Google Scholar]
  50. 50. 
    Peled A, Sarig O, Sun G, Samuelov L, Ma CA et al. 2019. Loss-of-function mutations in caspase recruitment domain-containing protein 14 (CARD14) are associated with a severe variant of atopic dermatitis. J. Allergy Clin. Immunol. 143:173–81.e10
    [Google Scholar]
  51. 51. 
    Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY et al. 2003. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J. Immunol. 171:3262–69
    [Google Scholar]
  52. 52. 
    Charbit-Henrion F, Jeverica AK, Begue B, Markelj G, Parlato M et al. 2017. Deficiency in mucosa-associated lymphoid tissue lymphoma translocation 1: a novel cause of IPEX-like syndrome. J. Pediatr. Gastroenterol. Nutr. 64:378–84
    [Google Scholar]
  53. 53. 
    Rozmus J, McDonald R, Fung SY, Del Bel KL, Roden J et al. 2016. Successful clinical treatment and functional immunological normalization of human MALT1 deficiency following hematopoietic stem cell transplantation. Clin. Immunol. 168:1–5
    [Google Scholar]
  54. 54. 
    McKinnon ML, Rozmus J, Fung SY, Hirschfeld AF, Del Bel KL et al. 2014. Combined immunodeficiency associated with homozygous MALT1 mutations. J. Allergy Clin. Immunol. 133:1458–62.e7
    [Google Scholar]
  55. 55. 
    Zigmond SH. 2000. How WASP regulates actin polymerization. J. Cell Biol. 150:F117–20
    [Google Scholar]
  56. 56. 
    Ochs HD. 2009. Mutations of the Wiskott-Aldrich Syndrome Protein affect protein expression and dictate the clinical phenotypes. Immunol. Res. 44:84–88
    [Google Scholar]
  57. 57. 
    Lexmond WS, Goettel JA, Lyons JJ, Jacobse J, Deken MM et al. 2016. FOXP3+ Tregs require WASP to restrain Th2-mediated food allergy. J. Clin. Investig. 126:4030–44
    [Google Scholar]
  58. 58. 
    Lanzi G, Moratto D, Vairo D, Masneri S, Delmonte O et al. 2012. A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP. J. Exp. Med. 209:29–34
    [Google Scholar]
  59. 59. 
    Kuijpers TW, Tool ATJ, van der Bijl I, de Boer M, van Houdt M et al. 2017. Combined immunodeficiency with severe inflammation and allergy caused by ARPC1B deficiency. J. Allergy Clin. Immunol. 140:273–77.e10
    [Google Scholar]
  60. 60. 
    Kahr WH, Pluthero FG, Elkadri A, Warner N, Drobac M et al. 2017. Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease. Nat. Commun. 8:14816
    [Google Scholar]
  61. 61. 
    Janssen E, Tohme M, Hedayat M, Leick M, Kumari S et al. 2016. A DOCK8-WIP-WASp complex links T cell receptors to the actin cytoskeleton. J. Clin. Investig. 126:3837–51
    [Google Scholar]
  62. 62. 
    Zhang Q, Davis JC, Lamborn IT, Freeman AF, Jing H et al. 2009. Combined immunodeficiency associated with DOCK8 mutations. N. Engl. J. Med. 361:2046–55
    [Google Scholar]
  63. 63. 
    Ogawa K, Tanaka Y, Uruno T, Duan X, Harada Y et al. 2014. DOCK5 functions as a key signaling adaptor that links FcεRI signals to microtubule dynamics during mast cell degranulation. J. Exp. Med. 211:1407–19
    [Google Scholar]
  64. 64. 
    Pivniouk VI, Snapper SB, Kettner A, Alenius H, Laouini D et al. 2003. Impaired signaling via the high-affinity IgE receptor in Wiskott-Aldrich syndrome protein-deficient mast cells. Int. Immunol. 15:1431–40
    [Google Scholar]
  65. 65. 
    Alroqi FJ, Charbonnier LM, Keles S, Ghandour F, Mouawad P et al. 2017. DOCK8 deficiency presenting as an IPEX-like disorder. J. Clin. Immunol. 37:811–19
    [Google Scholar]
  66. 66. 
    Humblet-Baron S, Sather B, Anover S, Becker-Herman S, Kasprowicz DJ et al. 2007. Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis. J. Clin. Investig. 117:407–18
    [Google Scholar]
  67. 67. 
    Maillard MH, Cotta-de-Almeida V, Takeshima F, Nguyen DD, Michetti P et al. 2007. The Wiskott-Aldrich syndrome protein is required for the function of CD4+CD25+Foxp3+ regulatory T cells. J. Exp. Med. 204:381–91
    [Google Scholar]
  68. 68. 
    Marangoni F, Trifari S, Scaramuzza S, Panaroni C, Martino S et al. 2007. WASP regulates suppressor activity of human and murine CD4+CD25+FOXP3+ natural regulatory T cells. J. Exp. Med. 204:369–80
    [Google Scholar]
  69. 69. 
    Tangye SG, Pillay B, Randall KL, Avery DT, Phan TG et al. 2017. Dedicator of cytokinesis 8-deficient CD4+ T cells are biased to a TH2 effector fate at the expense of TH1 and TH17 cells. J. Allergy Clin. Immunol. 139:933–49
    [Google Scholar]
  70. 70. 
    Taylor MD, Sadhukhan S, Kottangada P, Ramgopal A, Sarkar K et al. 2010. Nuclear role of WASp in the pathogenesis of dysregulated TH1 immunity in human Wiskott-Aldrich syndrome. Sci. Transl. Med. 2:37ra44
    [Google Scholar]
  71. 71. 
    Trifari S, Sitia G, Aiuti A, Scaramuzza S, Marangoni F et al. 2006. Defective Th1 cytokine gene transcription in CD4+ and CD8+ T cells from Wiskott-Aldrich syndrome patients. J. Immunol. 177:7451–61
    [Google Scholar]
  72. 72. 
    Morales-Tirado V, Sojka DK, Katzman SD, Lazarski CA, Finkelman FD et al. 2010. Critical requirement for the Wiskott-Aldrich syndrome protein in Th2 effector function. Blood 115:3498–507
    [Google Scholar]
  73. 73. 
    Roncagalli R, Cucchetti M, Jarmuzynski N, Gregoire C, Bergot E et al. 2016. The scaffolding function of the RLTPR protein explains its essential role for CD28 co-stimulation in mouse and human T cells. J. Exp. Med. 213:2437–57
    [Google Scholar]
  74. 74. 
    Wang Y, Ma CS, Ling Y, Bousfiha A, Camcioglu Y et al. 2016. Dual T cell– and B cell–intrinsic deficiency in humans with biallelic RLTPR mutations. J. Exp. Med. 213:2413–35
    [Google Scholar]
  75. 75. 
    Alazami AM, Al-Helale M, Alhissi S, Al-Saud B, Alajlan H et al. 2018. Novel CARMIL2 mutations in patients with variable clinical dermatitis, infections, and combined immunodeficiency. Front. Immunol. 9:203
    [Google Scholar]
  76. 76. 
    Schober T, Magg T, Laschinger M, Rohlfs M, Linhares ND et al. 2017. A human immunodeficiency syndrome caused by mutations in CARMIL2. Nat. Commun. 8:14209
    [Google Scholar]
  77. 77. 
    Tangye SG, Pelham SJ, Deenick EK, Ma CS 2017. Cytokine-mediated regulation of human lymphocyte development and function: insights from primary immunodeficiencies. J. Immunol. 199:1949–58
    [Google Scholar]
  78. 78. 
    Wood PM, Fieschi C, Picard C, Ottenhoff TH, Casanova JL, Kumararatne DS 2005. Inherited defects in the interferon-gamma receptor or interleukin-12 signalling pathways are not sufficient to cause allergic disease in children. Eur. J. Pediatr. 164:741–47
    [Google Scholar]
  79. 79. 
    Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G et al. 2007. STAT3 mutations in the hyper-IgE syndrome. N. Engl. J. Med. 357:1608–19
    [Google Scholar]
  80. 80. 
    Minegishi Y, Saito M, Tsuchiya S, Tsuge I, Takada H et al. 2007. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 448:1058–62
    [Google Scholar]
  81. 81. 
    Davis SD, Schaller J, Wedgwood RJ 1966. Job's syndrome: recurrent, “cold”, staphylococcal abscesses. Lancet 287:1013–15
    [Google Scholar]
  82. 82. 
    Buckley RH, Wray BB, Belmaker EZ 1972. Extreme hyperimmunoglobulinemia E and undue susceptibility to infection. Pediatrics 49:59–70
    [Google Scholar]
  83. 83. 
    Buckley RH. 2001. The hyper-IgE syndrome. Clin. Rev. Allergy Immunol. 20:139–54
    [Google Scholar]
  84. 84. 
    Gorin LJ, Jeha SC, Sullivan MP, Rosenblatt HM, Shearer WT 1989. Burkitt's lymphoma developing in a 7-year-old boy with hyper-IgE syndrome. J. Allergy Clin. Immunol. 83:5–10
    [Google Scholar]
  85. 85. 
    Kashef MA, Kashef S, Handjani F, Karimi M 2006. Hodgkin lymphoma developing in a 4.5-year-old girl with hyper-IgE syndrome. Pediatr. Hematol. Oncol. 23:59–63
    [Google Scholar]
  86. 86. 
    Chandesris MO, Melki I, Natividad A, Puel A, Fieschi C et al. 2012. Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey. Medicine 91:e1–19
    [Google Scholar]
  87. 87. 
    Siegel AM, Stone KD, Cruse G, Lawrence MG, Olivera A et al. 2013. Diminished allergic disease in patients with STAT3 mutations reveals a role for STAT3 signaling in mast cell degranulation. J. Allergy Clin. Immunol. 132:1388–96
    [Google Scholar]
  88. 88. 
    Ives ML, Ma CS, Palendira U, Chan A, Bustamante J et al. 2013. Signal transducer and activator of transcription 3 (STAT3) mutations underlying autosomal dominant hyper-IgE syndrome impair human CD8+ T-cell memory formation and function. J. Allergy Clin. Immunol. 132:400–11.e9
    [Google Scholar]
  89. 89. 
    Arora M, Bagi P, Strongin A, Heimall J, Zhao X et al. 2017. Gastrointestinal manifestations of STAT3-deficient hyper-IgE syndrome. J. Clin. Immunol. 37:695–700
    [Google Scholar]
  90. 90. 
    Boos AC, Hagl B, Schlesinger A, Halm BE, Ballenberger N et al. 2014. Atopic dermatitis, STAT3- and DOCK8-hyper-IgE syndromes differ in IgE-based sensitization pattern. Allergy 69:943–53
    [Google Scholar]
  91. 91. 
    Hox V, O'Connell MP, Lyons JJ, Sackstein P, Dimaggio T et al. 2016. Diminution of signal transducer and activator of transcription 3 signaling inhibits vascular permeability and anaphylaxis. J. Allergy Clin. Immunol. 138:187–99
    [Google Scholar]
  92. 92. 
    Erlich TH, Yagil Z, Kay G, Peretz A, Migalovich-Sheikhet H et al. 2014. Mitochondrial STAT3 plays a major role in IgE-antigen-mediated mast cell exocytosis. J. Allergy Clin. Immunol. 134:460–69
    [Google Scholar]
  93. 93. 
    Dascani P, Ding C, Kong X, Tieri D, Hu X et al. 2018. Transcription factor STAT3 serves as a negative regulator controlling IgE class switching in mice. Immunohorizons 2:349–62
    [Google Scholar]
  94. 94. 
    Kane A, Lau A, Brink R, Tangye SG, Deenick EK 2016. B-cell-specific STAT3 deficiency: insight into the molecular basis of autosomal-dominant hyper-IgE syndrome. J. Allergy Clin. Immunol. 138:1455–58.e3
    [Google Scholar]
  95. 95. 
    Wesemann DR, Magee JM, Boboila C, Calado DP, Gallagher MP et al. 2011. Immature B cells preferentially switch to IgE with increased direct Sμ to Sε recombination. J. Exp. Med. 208:2733–46
    [Google Scholar]
  96. 96. 
    Massaad MJ, Cangemi B, Al-Herz W, LeFranc G, Freeman A et al. 2017. DOCK8 and STAT3 dependent inhibition of IgE isotype switching by TLR9 ligation in human B cells. Clin. Immunol. 183:263–65
    [Google Scholar]
  97. 97. 
    Schopfer K, Feldges A, Baerlocher K, Parisot RF, Wilhelm JA, Matter L 1983. Systemic lupus erythematosus in Staphylococcus aureus hyperimmunoglobulinaemia E syndrome. Br. Med. J. 287:524–26
    [Google Scholar]
  98. 98. 
    Jacobs DH, Macher AM, Handler R, Bennett JE, Collen MJ, Gallin JI 1984. Esophageal cryptococcosis in a patient with the hyperimmunoglobulin E-recurrent infection (Job's) syndrome. Gastroenterology 87:201–3
    [Google Scholar]
  99. 99. 
    Leyh F, Wendt V, Scherer R 1986. [Systemic lupus erythematosus and hyper-IgE syndrome in a 13-year-old child]. Z. Hautkr. 61:611–14 In German )
    [Google Scholar]
  100. 100. 
    Borges WG, Hensley T, Carey JC, Petrak BA, Hill HR 1998. The face of Job. J. Pediatr. 133:303–5
    [Google Scholar]
  101. 101. 
    Grimbacher B, Holland SM, Gallin JI, Greenberg F, Hill SC et al. 1999. Hyper-IgE syndrome with recurrent infections–an autosomal dominant multisystem disorder. N. Engl. J. Med. 340:692–702
    [Google Scholar]
  102. 102. 
    Falah O, Thwaites SE, Chalmers RT 2012. Ruptured thoracoabdominal aneurysm in a 27-year-old with hyper IgE syndrome. J. Vasc. Surg. 55:830–32
    [Google Scholar]
  103. 103. 
    Kim Y, Nard JA, Saad A, Casselman J, Wessell KR et al. 2015. Cerebral aneurysm in a 12-year-old boy with a STAT3 mutation (hyper-IgE syndrome). Ann. Allergy Asthma Immunol. 114:430–31
    [Google Scholar]
  104. 104. 
    Ling JC, Freeman AF, Gharib AM, Arai AE, Lederman RJ et al. 2007. Coronary artery aneurysms in patients with hyper IgE recurrent infection syndrome. Clin. Immunol. 122:255–58
    [Google Scholar]
  105. 105. 
    Sharma A, Kumar S, Jagia P 2018. Pulmonary artery pseudoaneurysm in hyper-IgE syndrome: rare complication with successful endovascular management. Vasc. Endovasc. Surg. 52:375–77
    [Google Scholar]
  106. 106. 
    Takeuchi S, Wada K, Otani N, Nawashiro H 2012. Multiple intracranial aneurysms associated with hyper-IgE syndrome. Intern. Med. 51:515–16
    [Google Scholar]
  107. 107. 
    Freeman AF, Avila EM, Shaw PA, Davis J, Hsu AP et al. 2011. Coronary artery abnormalities in Hyper-IgE syndrome. J. Clin. Immunol. 31:338–45
    [Google Scholar]
  108. 108. 
    Beziat V, Li J, Lin JX, Ma CS, Li P et al. 2018. A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity. Sci. Immunol. 3:eaat4956
    [Google Scholar]
  109. 109. 
    Frey-Jakobs S, Hartberger JM, Fliegauf M, Bossen C, Wehmeyer ML et al. 2018. ZNF341 controls STAT3 expression and thereby immunocompetence. Sci. Immunol. 3:eaat4941
    [Google Scholar]
  110. 110. 
    Schwerd T, Twigg SRF, Aschenbrenner D, Manrique S, Miller KA et al. 2017. A biallelic mutation in IL6ST encoding the GP130 co-receptor causes immunodeficiency and craniosynostosis. J. Exp. Med. 214:2547–62
    [Google Scholar]
  111. 111. 
    Shahin T, Aschenbrenner D, Cagdas D, Bal SK, Conde CD et al. 2019. Selective loss of function variants in IL6ST cause Hyper-IgE syndrome with distinct impairments of T-cell phenotype and function. Haematologica 104:609–21
    [Google Scholar]
  112. 112. 
    Ozaki K, Spolski R, Feng CG, Qi CF, Cheng J et al. 2002. A critical role for IL-21 in regulating immunoglobulin production. Science 298:1630–34
    [Google Scholar]
  113. 113. 
    Pesce J, Kaviratne M, Ramalingam TR, Thompson RW, Urban JF Jr et al. 2006. The IL-21 receptor augments Th2 effector function and alternative macrophage activation. J. Clin. Investig. 116:2044–55
    [Google Scholar]
  114. 114. 
    Neveu WA, Allard JB, Dienz O, Wargo MJ, Ciliberto G et al. 2009. IL-6 is required for airway mucus production induced by inhaled fungal allergens. J. Immunol. 183:1732–38
    [Google Scholar]
  115. 115. 
    Suto A, Nakajima H, Hirose K, Suzuki K, Kagami S et al. 2002. Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line Cε transcription of IL-4-stimulated B cells. Blood 100:4565–73
    [Google Scholar]
  116. 116. 
    Kishida T, Hiromura Y, Shin-Ya M, Asada H, Kuriyama H et al. 2007. IL-21 induces inhibitor of differentiation 2 and leads to complete abrogation of anaphylaxis in mice. J. Immunol. 179:8554–61
    [Google Scholar]
  117. 117. 
    Avery DT, Ma CS, Bryant VL, Santner-Nanan B, Nanan R et al. 2008. STAT3 is required for IL-21-induced secretion of IgE from human naive B cells. Blood 112:1784–93
    [Google Scholar]
  118. 118. 
    Kotlarz D, Zietara N, Milner JD, Klein C 2014. Human IL-21 and IL-21R deficiencies: two novel entities of primary immunodeficiency. Curr. Opin. Pediatr. 26:704–12
    [Google Scholar]
  119. 119. 
    Kotlarz D, Zietara N, Uzel G, Weidemann T, Braun CJ et al. 2013. Loss-of-function mutations in the IL-21 receptor gene cause a primary immunodeficiency syndrome. J. Exp. Med. 210:433–43
    [Google Scholar]
  120. 120. 
    Palomares O, Martin-Fontecha M, Lauener R, Traidl-Hoffmann C, Cavkaytar O et al. 2014. Regulatory T cells and immune regulation of allergic diseases: roles of IL-10 and TGF-β. Genes Immun 15:511–20
    [Google Scholar]
  121. 121. 
    Engelhardt KR, Shah N, Faizura-Yeop I, Kocacik Uygun DF, Frede N et al. 2013. Clinical outcome in IL-10- and IL-10 receptor-deficient patients with or without hematopoietic stem cell transplantation. J. Allergy Clin. Immunol. 131:825–30
    [Google Scholar]
  122. 122. 
    Spencer S, Kostel Bal S, Egner W, Lango Allen H, Raza SI et al. 2019. Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses. J. Exp. Med. 216:1986–98
    [Google Scholar]
  123. 123. 
    Ferreira RC, Freitag DF, Cutler AJ, Howson JM, Rainbow DB et al. 2013. Functional IL6R 358Ala allele impairs classical IL-6 receptor signaling and influences risk of diverse inflammatory diseases. PLOS Genet 9:e1003444
    [Google Scholar]
  124. 124. 
    Wang Y, Hu H, Wu J, Zhao X, Zhen Y et al. 2016. The IL6R gene polymorphisms are associated with sIL-6R, IgE and lung function in Chinese patients with asthma. Gene 585:51–57
    [Google Scholar]
  125. 125. 
    Esparza-Gordillo J, Schaarschmidt H, Liang L, Cookson W, Bauerfeind A et al. 2013. A functional IL-6 receptor (IL6R) variant is a risk factor for persistent atopic dermatitis. J. Allergy Clin. Immunol. 132:371–77
    [Google Scholar]
  126. 126. 
    Puel A, Picard C, Lorrot M, Pons C, Chrabieh M et al. 2008. Recurrent staphylococcal cellulitis and subcutaneous abscesses in a child with autoantibodies against IL-6. J. Immunol. 180:647–54
    [Google Scholar]
  127. 127. 
    Ma CA, Xi L, Cauff B, DeZure A, Freeman AF et al. 2017. Somatic STAT5b gain-of-function mutations in early onset nonclonal eosinophilia, urticaria, dermatitis, and diarrhea. Blood 129:650–53
    [Google Scholar]
  128. 128. 
    Ando T, Xiao W, Gao P, Namiranian S, Matsumoto K et al. 2014. Critical role for mast cell Stat5 activity in skin inflammation. Cell Rep 6:366–76
    [Google Scholar]
  129. 129. 
    Kawakami T, Ando T, Kawakami Y 2015. Hypothetical atopic dermatitis-myeloproliferative neoplasm syndrome. Front. Immunol. 6:434
    [Google Scholar]
  130. 130. 
    Bandapalli OR, Schuessele S, Kunz JB, Rausch T, Stutz AM et al. 2014. The activating STAT5B N642H mutation is a common abnormality in pediatric T-cell acute lymphoblastic leukemia and confers a higher risk of relapse. Haematologica 99:e188–92
    [Google Scholar]
  131. 131. 
    Kucuk C, Jiang B, Hu X, Zhang W, Chan JK et al. 2015. Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells. Nat. Commun. 6:6025
    [Google Scholar]
  132. 132. 
    Rajala HL, Eldfors S, Kuusanmaki H, van Adrichem AJ, Olson T et al. 2013. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood 121:4541–50
    [Google Scholar]
  133. 133. 
    Cross NCP, Hoade Y, Tapper WJ, Carreno-Tarragona G, Fanelli T et al. 2019. Recurrent activating STAT5B N642H mutation in myeloid neoplasms with eosinophilia. Leukemia 33:415–25
    [Google Scholar]
  134. 134. 
    Del Bel KL, Ragotte RJ, Saferali A, Lee S, Vercauteren SM et al. 2017. JAK1 gain-of-function causes an autosomal dominant immune dysregulatory and hypereosinophilic syndrome. J. Allergy Clin. Immunol. 139:2016–20.e5
    [Google Scholar]
  135. 135. 
    Minegishi Y, Saito M, Morio T, Watanabe K, Agematsu K et al. 2006. Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity 25:745–55
    [Google Scholar]
  136. 136. 
    Kreins AY, Ciancanelli MJ, Okada S, Kong XF, Ramirez-Alejo N et al. 2015. Human TYK2 deficiency: mycobacterial and viral infections without hyper-IgE syndrome. J. Exp. Med. 212:1641–62
    [Google Scholar]
  137. 137. 
    Rawson R, Yang T, Newbury RO, Aquino M, Doshi A et al. 2016. TGF-β1-induced PAI-1 contributes to a profibrotic network in patients with eosinophilic esophagitis. J. Allergy Clin. Immunol. 138:791–800.e4
    [Google Scholar]
  138. 138. 
    Balzar S, Chu HW, Silkoff P, Cundall M, Trudeau JB et al. 2005. Increased TGF-β2 in severe asthma with eosinophilia. J. Allergy Clin. Immunol. 115:110–17
    [Google Scholar]
  139. 139. 
    Kotlarz D, Marquardt B, Baroy T, Lee WS, Konnikova L et al. 2018. Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy. Nat. Genet. 50:344–48
    [Google Scholar]
  140. 140. 
    Kinoshita A, Saito T, Tomita H, Makita Y, Yoshida K et al. 2000. Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease. Nat. Genet. 26:19–20
    [Google Scholar]
  141. 141. 
    Abonia JP, Wen T, Stucke EM, Grotjan T, Griffith MS et al. 2013. High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders. J. Allergy Clin. Immunol. 132:378–86
    [Google Scholar]
  142. 142. 
    Morgan AW, Pearson SB, Davies S, Gooi HC, Bird HA 2007. Asthma and airways collapse in two heritable disorders of connective tissue. Ann. Rheum. Dis. 66:1369–73
    [Google Scholar]
  143. 143. 
    Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH et al. 2006. Aneurysm syndromes caused by mutations in the TGF-β receptor. N. Engl. J. Med. 355:788–98
    [Google Scholar]
  144. 144. 
    Dewan AK, Tomlinson RE, Mitchell S, Goh BC, Yung RM et al. 2015. Dysregulated TGF-β signaling alters bone microstructure in a mouse model of Loeys-Dietz syndrome. J. Orthop. Res. 33:1447–54
    [Google Scholar]
  145. 145. 
    Frischmeyer-Guerrerio PA, Guerrerio AL, Oswald G, Chichester K, Myers L et al. 2013. TGFβ receptor mutations impose a strong predisposition for human allergic disease. Sci. Transl. Med. 5:195ra94
    [Google Scholar]
  146. 146. 
    Dietz HC, Cutting GR, Pyeritz RE, Maslen CL, Sakai LY et al. 1991. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 352:337–39
    [Google Scholar]
  147. 147. 
    Schalkwijk J, Zweers MC, Steijlen PM, Dean WB, Taylor G et al. 2001. A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency. N. Engl. J. Med. 345:1167–75
    [Google Scholar]
  148. 148. 
    Lindsay ME, Dietz HC. 2014. The genetic basis of aortic aneurysm. Cold Spring Harb. Perspect. Med. 4:a015909
    [Google Scholar]
  149. 149. 
    Lyons JJ, Liu Y, Ma CA, Yu X, O'Connell MP et al. 2017. ERBIN deficiency links STAT3 and TGF-β pathway defects with atopy in humans. J. Exp. Med 214:669–80 Correction. 2017 J. Exp. Med 214:1201
    [Google Scholar]
  150. 150. 
    Chen C, Akiyama K, Wang D, Xu X, Li B et al. 2015. mTOR inhibition rescues osteopenia in mice with systemic sclerosis. J. Exp. Med. 212:73–91
    [Google Scholar]
  151. 151. 
    Hershey GK, Friedrich MF, Esswein LA, Thomas ML, Chatila TA 1997. The association of atopy with a gain-of-function mutation in the α subunit of the interleukin-4 receptor. N. Engl. J. Med. 337:1720–25
    [Google Scholar]
  152. 152. 
    Oetjen LK, Mack MR, Feng J, Whelan TM, Niu H et al. 2017. Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch. Cell 171:217–28.e13
    [Google Scholar]
  153. 153. 
    Brunkow ME, Jeffery EW, Hjerrild KA, Paeper B, Clark LB et al. 2001. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 27:68–73
    [Google Scholar]
  154. 154. 
    Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ et al. 2001. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 27:20–21
    [Google Scholar]
  155. 155. 
    Wildin RS, Ramsdell F, Peake J, Faravelli F, Casanova JL et al. 2001. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat. Genet. 27:18–20
    [Google Scholar]
  156. 156. 
    Chatila TA, Blaeser F, Ho N, Lederman HM, Voulgaropoulos C et al. 2000. JM2, encoding a fork head–related protein, is mutated in X-linked autoimmunity–allergic disregulation syndrome. J. Clin. Investig. 106:R75–81
    [Google Scholar]
  157. 157. 
    Ramsdell F, Ziegler SF. 2014. FOXP3 and scurfy: how it all began. Nat. Rev. Immunol. 14:343–49
    [Google Scholar]
  158. 158. 
    Caudy AA, Reddy ST, Chatila T, Atkinson JP, Verbsky JW 2007. CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome, and defective IL-10 expression from CD4 lymphocytes. J. Allergy Clin. Immunol. 119:482–87
    [Google Scholar]
  159. 159. 
    Nadeau K, Hwa V, Rosenfeld RG 2011. STAT5b deficiency: an unsuspected cause of growth failure, immunodeficiency, and severe pulmonary disease. J. Pediatr. 158:701–8
    [Google Scholar]
  160. 160. 
    Kanai T, Jenks J, Nadeau KC 2012. The STAT5b pathway defect and autoimmunity. Front. Immunol. 3:234
    [Google Scholar]
  161. 161. 
    Josefowicz SZ, Niec RE, Kim HY, Treuting P, Chinen T et al. 2012. Extrathymically generated regulatory T cells control mucosal TH2 inflammation. Nature 482:395–99
    [Google Scholar]
  162. 162. 
    Van Gool F, Nguyen MLT, Mumbach MR, Satpathy AT, Rosenthal WL et al. 2019. A mutation in the transcription factor Foxp3 drives T helper 2 effector function in regulatory T cells. Immunity 50:362–77.e6
    [Google Scholar]
  163. 163. 
    Sandilands A, Sutherland C, Irvine AD, McLean WH 2009. Filaggrin in the frontline: role in skin barrier function and disease. J. Cell Sci. 122:1285–94
    [Google Scholar]
  164. 164. 
    Smith FJ, Irvine AD, Terron-Kwiatkowski A, Sandilands A, Campbell LE et al. 2006. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat. Genet. 38:337–42
    [Google Scholar]
  165. 165. 
    Sandilands A, Terron-Kwiatkowski A, Hull PR, O'Regan GM, Clayton TH et al. 2007. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat. Genet. 39:650–54
    [Google Scholar]
  166. 166. 
    Irvine AD, McLean WH, Leung DY 2011. Filaggrin mutations associated with skin and allergic diseases. N. Engl. J. Med. 365:1315–27
    [Google Scholar]
  167. 167. 
    Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M et al. 2007. Cytokine modulation of atopic dermatitis filaggrin skin expression. J. Allergy Clin. Immunol. 120:150–55
    [Google Scholar]
  168. 168. 
    Hvid M, Vestergaard C, Kemp K, Christensen GB, Deleuran B, Deleuran M 2011. IL-25 in atopic dermatitis: a possible link between inflammation and skin barrier dysfunction. ? J. Investig. Dermatol. 131:150–57
    [Google Scholar]
  169. 169. 
    Kottke MD, Delva E, Kowalczyk AP 2006. The desmosome: cell science lessons from human diseases. J. Cell Sci. 119:797–806
    [Google Scholar]
  170. 170. 
    Jonca N, Leclerc EA, Caubet C, Simon M, Guerrin M, Serre G 2011. Corneodesmosomes and corneodesmosin: from the stratum corneum cohesion to the pathophysiology of genodermatoses. Eur. J. Dermatol. 21:Suppl. 235–42
    [Google Scholar]
  171. 171. 
    Oji V, Eckl KM, Aufenvenne K, Natebus M, Tarinski T et al. 2010. Loss of corneodesmosin leads to severe skin barrier defect, pruritus, and atopy: unraveling the peeling skin disease. Am. J. Hum. Genet. 87:274–81
    [Google Scholar]
  172. 172. 
    McAleer MA, Pohler E, Smith FJ, Wilson NJ, Cole C et al. 2015. Severe dermatitis, multiple allergies, and metabolic wasting syndrome caused by a novel mutation in the N-terminal plakin domain of desmoplakin. J. Allergy Clin. Immunol. 136:1268–76
    [Google Scholar]
  173. 173. 
    Samuelov L, Sarig O, Harmon RM, Rapaport D, Ishida-Yamamoto A et al. 2013. Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nat. Genet. 45:1244–48
    [Google Scholar]
  174. 174. 
    Ishida-Yamamoto A, Deraison C, Bonnart C, Bitoun E, Robinson R et al. 2005. LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum. J. Investig. Dermatol. 124:360–66
    [Google Scholar]
  175. 175. 
    Chavanas S, Bodemer C, Rochat A, Hamel-Teillac D, Ali M et al. 2000. Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat. Genet. 25:141–42
    [Google Scholar]
  176. 176. 
    Jungersted JM, Scheer H, Mempel M, Baurecht H, Cifuentes L et al. 2010. Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema. Allergy 65:911–18
    [Google Scholar]
  177. 177. 
    Kezic S, O'Regan GM, Lutter R, Jakasa I, Koster ES et al. 2012. Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency. J. Allergy Clin. Immunol. 129:1031–39.e1
    [Google Scholar]
  178. 178. 
    Miajlovic H, Fallon PG, Irvine AD, Foster TJ 2010. Effect of filaggrin breakdown products on growth of and protein expression by Staphylococcus aureus. J. Allergy Clin. . Immunol 126:1184–90.e3
    [Google Scholar]
  179. 179. 
    Simpson EL, Chalmers JR, Hanifin JM, Thomas KS, Cork MJ et al. 2014. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J. Allergy Clin. Immunol. 134:818–23
    [Google Scholar]
  180. 180. 
    Kaplan AP, Beaven MA. 1976. In vivo studies of the pathogenesis of cold urticaria, cholinergic urticaria, and vibration-induced swelling. J. Investig. Dermatol. 67:327–32
    [Google Scholar]
  181. 181. 
    Ombrello MJ, Remmers EF, Sun G, Freeman AF, Datta S et al. 2012. Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. N. Engl. J. Med. 366:330–38
    [Google Scholar]
  182. 182. 
    Gandhi C, Healy C, Wanderer AA, Hoffman HM 2009. Familial atypical cold urticaria: description of a new hereditary disease. J. Allergy Clin. Immunol. 124:1245–50
    [Google Scholar]
  183. 183. 
    Aderibigbe OM, Priel DL, Lee CC, Ombrello MJ, Prajapati VH et al. 2015. Distinct cutaneous manifestations and cold-induced leukocyte activation associated with PLCG2 mutations. JAMA Dermatol 151:627–34
    [Google Scholar]
  184. 184. 
    Schade A, Walliser C, Wist M, Haas J, Vatter P et al. 2016. Cool-temperature-mediated activation of phospholipase C-γ2 in the human hereditary disease PLAID. Cell Signal 28:1237–51
    [Google Scholar]
  185. 185. 
    Wang J, Sohn H, Sun G, Milner JD, Pierce SK 2014. The autoinhibitory C-terminal SH2 domain of phospholipase C-γ2 stabilizes B cell receptor signalosome assembly. Sci. Signal. 7:ra89
    [Google Scholar]
  186. 186. 
    Aksentijevich I, Putnam CD, Remmers EF, Mueller JL, Le J et al. 2007. The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum 56:1273–85
    [Google Scholar]
  187. 187. 
    Boyden SE, Desai A, Cruse G, Young ML, Bolan HC et al. 2016. Vibratory urticaria associated with a missense variant in ADGRE2. N. Engl. J. Med. 374:656–63
    [Google Scholar]
  188. 188. 
    Huang YS, Chiang NY, Hu CH, Hsiao CC, Cheng KF et al. 2012. Activation of myeloid cell-specific adhesion class G protein-coupled receptor EMR2 via ligation-induced translocation and interaction of receptor subunits in lipid raft microdomains. Mol. Cell. Biol. 32:1408–20
    [Google Scholar]
  189. 189. 
    Lyons JJ, Yu X, Hughes JD, Le QT, Jamil A et al. 2016. Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number. Nat. Genet. 48:1564–69
    [Google Scholar]
  190. 190. 
    Lyons JJ, Sun G, Stone KD, Nelson C, Wisch L et al. 2014. Mendelian inheritance of elevated serum tryptase associated with atopy and connective tissue abnormalities. J. Allergy Clin. Immunol. 133:1471–74
    [Google Scholar]
  191. 191. 
    Ui H, Andoh T, Lee JB, Nojima H, Kuraishi Y 2006. Potent pruritogenic action of tryptase mediated by PAR-2 receptor and its involvement in anti-pruritic effect of nafamostat mesilate in mice. Eur. J. Pharmacol. 530:172–78
    [Google Scholar]
  192. 192. 
    Sommerhoff CP. 2001. Mast cell tryptases and airway remodeling. Am. J. Respir. Crit. Care Med. 164:S52–58
    [Google Scholar]
  193. 193. 
    Doong JC, Chichester K, Oliver ET, Schwartz LB, Saini SS 2017. Chronic idiopathic urticaria: systemic complaints and their relationship with disease and immune measures. J. Allergy Clin. Immunol. Pract. 5:1314–18
    [Google Scholar]
  194. 194. 
    Fellinger C, Hemmer W, Wohrl S, Sesztak-Greinecker G, Jarisch R, Wantke F 2014. Clinical characteristics and risk profile of patients with elevated baseline serum tryptase. Allergol. Immunopathol. 42:544–52
    [Google Scholar]
  195. 195. 
    Kucharewicz I, Bodzenta-Lukaszyk A, Szymanski W, Mroczko B, Szmitkowski M 2007. Basal serum tryptase level correlates with severity of hymenoptera sting and age. J. Investig. Allergol. Clin. Immunol. 17:65–69
    [Google Scholar]
  196. 196. 
    Sahiner UM, Yavuz ST, Buyuktiryaki B, Cavkaytar O, Yilmaz EA et al. 2014. Serum basal tryptase may be a good marker for predicting the risk of anaphylaxis in children with food allergy. Allergy 69:265–68
    [Google Scholar]
  197. 197. 
    Valent P, Akin C, Metcalfe DD 2017. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood 129:1420–27
    [Google Scholar]
  198. 198. 
    Le QT, Lyons JJ, Naranjo AN, Olivera A, Lazarus RA et al. 2019. Impact of naturally forming human α/β-tryptase heterotetramers in the pathogenesis of hereditary α-tryptasemia. J. Exp. Med. 216:2348–61
    [Google Scholar]
  199. 199. 
    Bernth-Jensen JM, Holm M, Christiansen M 2016. Neonatal-onset TBNK+ severe combined immunodeficiency and neutropenia caused by mutated phosphoglucomutase 3. J. Allergy Clin. Immunol. 137:321–24
    [Google Scholar]
  200. 200. 
    Sassi A, Lazaroski S, Wu G, Haslam SM, Fliegauf M et al. 2014. Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. J. Allergy Clin. Immunol. 133:1410–19.e13
    [Google Scholar]
  201. 201. 
    Stray-Pedersen A, Backe PH, Sorte HS, Morkrid L, Chokshi NY et al. 2014. PGM3 mutations cause a congenital disorder of glycosylation with severe immunodeficiency and skeletal dysplasia. Am. J. Hum. Genet. 95:96–107
    [Google Scholar]
  202. 202. 
    Zhang Y, Yu X, Ichikawa M, Lyons JJ, Datta S et al. 2014. Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment. J. Allergy Clin. Immunol. 133:1400–9.e5
    [Google Scholar]
  203. 203. 
    Ben-Khemis L, Mekki N, Ben-Mustapha I, Rouault K, Mellouli F et al. 2017. A founder mutation underlies a severe form of phosphoglutamase 3 (PGM3) deficiency in Tunisian patients. Mol. Immunol. 90:57–63
    [Google Scholar]
  204. 204. 
    Carlson RJ, Bond MR, Hutchins S, Brown Y, Wolfe LA et al. 2017. Detection of phosphoglucomutase-3 deficiency by lectin-based flow cytometry. J. Allergy Clin. Immunol. 140:291–94.e4
    [Google Scholar]
  205. 205. 
    Wu G, Hitchen PG, Panico M, North SJ, Barbouche MR et al. 2016. Glycoproteomic studies of IgE from a novel hyper IgE syndrome linked to PGM3 mutation. Glycoconj. J. 33:447–56
    [Google Scholar]
  206. 206. 
    Tanoue A, Endo F, Kitano A, Matsuda I 1990. A single nucleotide change in the prolidase gene in fibroblasts from two patients with polypeptide positive prolidase deficiency: expression of the mutant enzyme in NIH 3T3 cells. J. Clin. Investig. 86:351–55
    [Google Scholar]
  207. 207. 
    Fukumura A, Asaka T, Kasakura H, Doshita T, Chen W et al. 2009. [Prolidase deficiency with various clinical conditions including hyper-IgE and multiple lung bulla formation]. Nihon Naika Gakkai Zasshi 98:150–52 In Japanese )
    [Google Scholar]
  208. 208. 
    Hershkovitz T, Hassoun G, Indelman M, Shlush LI, Bergman R et al. 2006. A homozygous missense mutation in PEPD encoding peptidase D causes prolidase deficiency associated with hyper-IgE syndrome. Clin. Exp. Dermatol. 31:435–40
    [Google Scholar]
  209. 209. 
    Lopes I, Marques L, Neves E, Silva A, Taveira M et al. 2002. Prolidase deficiency with hyperimmunoglobulin E: a case report. Pediatr. Allergy Immunol. 13:140–42
    [Google Scholar]
  210. 210. 
    Viglio S, Annovazzi L, Conti B, Genta I, Perugini P et al. 2006. The role of emerging techniques in the investigation of prolidase deficiency: from diagnosis to the development of a possible therapeutical approach. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 832:1–8
    [Google Scholar]
  211. 211. 
    Lubick KJ, Robertson SJ, McNally KL, Freedman BA, Rasmussen AL et al. 2015. Flavivirus antagonism of type I interferon signaling reveals prolidase as a regulator of IFNAR1 surface expression. Cell Host Microbe 18:61–74
    [Google Scholar]
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