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Immunoglobulin E and Allergy: Antibodies in Immune Inflammation and Treatment

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  • Authors: Sophia N. Karagiannis1, Panagiotis Karagiannis2, Debra H. Josephs3, Louise Saul4, Amy E. Gilbert5, Nadine Upton6, Hannah J. Gould7
  • Editor: Diana Boraschi8
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Cutaneous Medicine and Immunotherapy Unit, St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine & NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London School of Medicine, Guy's Hospital, King's College London, London SE1 9RT, United Kingdom; 2: Cutaneous Medicine and Immunotherapy Unit, St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine & NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London School of Medicine, Guy's Hospital, King's College London, London SE1 9RT, United Kingdom; 3: Cutaneous Medicine and Immunotherapy Unit, St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine & NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London School of Medicine, Guy's Hospital, King's College London, London SE1 9RT, United Kingdom; 4: Cutaneous Medicine and Immunotherapy Unit, St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine & NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London School of Medicine, Guy's Hospital, King's College London, London SE1 9RT, United Kingdom; 5: Cutaneous Medicine and Immunotherapy Unit, St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine & NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London School of Medicine, Guy's Hospital, King's College London, London SE1 9RT, United Kingdom; 6: Randall Division of Cell and Molecular Biophysics, Division of Asthma, Allergy, and Lung Biology, MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, United Kingdom; 7: Randall Division of Cell and Molecular Biophysics, Division of Asthma, Allergy, and Lung Biology, MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, United Kingdom; 8: National Research Council, Pisa, Italy
    • Source: microbiolspec October 2013 vol. 1 no. 1 doi:10.1128/microbiolspec.AID-0006-2012
  • Received 24 October 2012 Accepted 21 March 2013 Published 25 October 2013
  • Sophia N. Karagiannis, [email protected]
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  • Abstract:

    The pathogenic role of immunoglobulin E (IgE) antibodies in triggering and maintaining allergic inflammation in response to allergens is due to the binding of multivalent allergens to allergen-specific IgEs on sensitized effector cells. These interactions trigger effector cell activation, resulting in release of potent inflammatory mediators, recruitment of inflammatory cells, antigen presentation, and production of allergen-specific antibody responses. Since its discovery in the 1960s, the central role of IgE in allergic disease has been intensively studied, placing IgE and its functions at the heart of therapeutic efforts for the treatment of allergies. Here, we provide an overview of the nature, roles, and significance of IgE antibodies in allergic diseases, infections, and inflammation and the utility of antibodies as therapies. We place special emphasis on allergen-IgE-Fcε receptor complexes in the context of allergic and inflammatory diseases and describe strategies, including monoclonal antibodies, aimed at interrupting these complexes. Of clinical significance, one antibody, omalizumab, is presently in clinical use and works by preventing formation of IgE-Fcε receptor interactions. Active immunotherapy approaches with allergens and allergen derivatives have also demonstrated clinical benefits for patients with allergic diseases. These treatments are strongly associated with serum increases of IgE-neutralizing antibodies and feature a notable redirection of humoral responses towards production of antibodies of the IgG4 subclass in patients receiving immunotherapies. Lastly, we provide a new perspective on the rise of recombinant antibodies of the IgE class recognizing tumor-associated antigens, and we discuss the potential utility of tumor antigen-specific IgE antibodies to direct potent IgE-driven immune responses against tumors.

  • Citation: Karagiannis S, Karagiannis P, Josephs D, Saul L, Gilbert A, Upton N, Gould H. 2013. Immunoglobulin E and Allergy: Antibodies in Immune Inflammation and Treatment. Microbiol Spectrum 1(1):AID-0006-2012. doi:10.1128/microbiolspec.AID-0006-2012.

Key Concept Ranking

Immune Receptors
0.5121212
Mast Cells
0.47567698
Major Histocompatibility Complex Class II
0.44351926
Immune Cells
0.4186722
0.5121212

References

1. Galli SJ, Tsai M, Piliponsky AM. 2008. The development of allergic inflammation. Nature 454:445–454.
2. Oppenheimer J, Nelson HS. 2006. Skin testing. Ann Allergy Asthma Immunol 96:S6–S12.
3. Bernstein IL, Li JT, Bernstein DI, Hamilton R, Spector SL, Tan R, Sicherer S, Golden DB, Khan DA, Nicklas RA, Portnoy JM, Blessing-Moore J, Cox L, Lang DM, Oppenheimer J, Randolph CC, Schuller DE, Tilles SA, Wallace DV, Levetin E, Weber R. 2008. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol 100:S1–S148. [PubMed][CrossRef]
4. Akhabir L, Sandford AJ. 2011. Genome-wide association studies for discovery of genes involved in asthma. Respirology 16:396–406. [PubMed][CrossRef]
5. Valenta R, Ball T, Focke M, Linhart B, Mothes N, Niederberger V, Spitzauer S, Swoboda I, Vrtala S, Westritschnig K, Kraft D. 2004. Immunotherapy of allergic disease. Adv Immunol 82:105–153.
6. Barnes PJ. 2011. Pathophysiology of allergic inflammation. Immunol Rev 242:31–50. [PubMed][CrossRef]
7. Johansson SG, Bennich H. 1967. Immunological studies of an atypical (myeloma) immunoglobulin. Immunology 13:381–394. [PubMed]
8. Ishizaka K, Ishizaka T, Hornbrook MM. 1966. Physico-chemical properties of human reaginic antibody. IV. Presence of a unique immunoglobulin as a carrier of reaginic activity. J Immunol 97:75–85. [PubMed]
9. Geha RS, Jabara HH, Brodeur SR. 2003. The regulation of immunoglobulin E class-switch recombination. Nat Rev Immunol 3:721–732. [PubMed][CrossRef]
10. Gould HJ, Sutton BJ. 2008. IgE in allergy and asthma today. Nat Rev Immunol 8:205–217. [PubMed][CrossRef]
11. Galli SJ, Tsai M. 2012. IgE and mast cells in allergic disease. Nat Med 18:693–704. [PubMed][CrossRef]
12. Dhaliwal B, Yuan D, Pang MO, Henry AJ, Cain K, Oxbrow A, Fabiane SM, Beavil AJ, McDonnell JM, Gould HJ, Sutton BJ. 2012. Crystal structure of IgE bound to its B-cell receptor CD23 reveals a mechanism of reciprocal allosteric inhibition with high affinity receptor FcepsilonRI. Proc Natl Acad Sci USA 109:12686–12691. [PubMed][CrossRef]
13. Kraft S, Kinet JP. 2007. New developments in FcepsilonRI regulation, function and inhibition. Nat Rev Immunol 7:365–378. [PubMed][CrossRef]
14. Dullaers M, De Bruyne R, Ramadani F, Gould HJ, Gevaert P, Lambrecht BN. 2012. The who, where, and when of IgE in allergic airway disease. J Allergy Clin Immunol 129:635–645. [PubMed][CrossRef]
15. Acharya M, Borland G, Edkins AL, Maclellan LM, Matheson J, Ozanne BW, Cushley W. 2010. CD23/FcepsilonRII: molecular multi-tasking. Clin Exp Immunol 162:12–23.
16. Dierks SE, Bartlett WC, Edmeades RL, Gould HJ, Rao M, Conrad DH. 1993. The oligomeric nature of the murine Fc epsilon RII/CD23. Implications for function. J Immunol 150:2372–2382. [PubMed]
17. Vouldoukis I, Mazier D, Moynet D, Thiolat D, Malvy D, Mossalayi MD. 2011. IgE mediates killing of intracellular Toxoplasma gondii by human macrophages through CD23-dependent, interleukin-10 sensitive pathway. PLoS One 6:e18289. [PubMed][CrossRef]
18. Vouldoukis I, Riveros-Moreno V, Dugas B, Ouaaz F, Becherel P, Debre P, Moncada S, Mossalayi MD. 1995. The killing of Leishmania major by human macrophages is mediated by nitric oxide induced after ligation of the Fc epsilon RII/CD23 surface antigen. Proc Natl Acad Sci USA 92:7804–7808. [PubMed][CrossRef]
19. Chen HY, Liu FT, Yang RY. 2005. Roles of galectin-3 in immune responses. Arch Immunol Ther Exp (Warsaw) 53:497–504. [PubMed]
20. Bax HJ, Keeble AH, Gould HJ. 2012. Cytokinergic IgE action in mast cell activation. Front Immunol 3:229. [PubMed][CrossRef]
21. Ziegler SF, Artis D. 2010. Sensing the outside world: TSLP regulates barrier immunity. Nat Immunol 11:289–293. [PubMed][CrossRef]
22. Fort MM, Cheung J, Yen D, Li J, Zurawski SM, Lo S, Menon S, Clifford T, Hunte B, Lesley R, Muchamuel T, Hurst SD, Zurawski G, Leach MW, Gorman DM, Rennick DM. 2001. IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity 15:985–995. [PubMed]
23. Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, Gorman DM, Bazan JF, Kastelein RA. 2005. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23:479–490. [PubMed][CrossRef]
24. Lambrecht BN, Hammad H. 2010. The role of dendritic and epithelial cells as master regulators of allergic airway inflammation. Lancet 376:835–843. [PubMed][CrossRef]
25. Sokol CL, Chu NQ, Yu S, Nish SA, Laufer TM, Medzhitov R. 2009. Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response. Nat Immunol 10:713–720. [PubMed][CrossRef]
26. Yoshimoto T, Yasuda K, Tanaka H, Nakahira M, Imai Y, Fujimori Y, Nakanishi K. 2009. Basophils contribute to T(H)2-IgE responses in vivo via IL-4 production and presentation of peptide-MHC class II complexes to CD4 + T cells. Nat Immunol 10:706–712. [PubMed][CrossRef]
27. Perrigoue JG, Saenz SA, Siracusa MC, Allenspach EJ, Taylor BC, Giacomin PR, Nair MG, Du Y, Zaph C, van Rooijen N, Comeau MR, Pearce EJ, Laufer TM, Artis D. 2009. MHC class II-dependent basophil-CD4 + T cell interactions promote T(H)2 cytokine-dependent immunity. Nat Immunol 10:697–705.
28. Saenz SA, Siracusa MC, Perrigoue JG, Spencer SP, Urban JF, Jr, Tocker JE, Budelsky AL, Kleinschek MA, Kastelein RA, Kambayashi T, Bhandoola A, Artis D. 2010. IL25 elicits a multipotent progenitor cell population that promotes T(H)2 cytokine responses. Nature 464:1362–1366. [PubMed][CrossRef]
29. Karagiannis SN, Warrack JK, Jennings KH, Murdock PR, Christie G, Moulder K, Sutton BJ, Gould HJ. 2001. Endocytosis and recycling of the complex between CD23 and HLA-DR in human B cells. Immunology 103:319–331. [PubMed]
30. Mudde GC, Bheekha R, Bruijnzeel-Koomen CA. 1995. Consequences of IgE/CD23-mediated antigen presentation in allergy. Immunol Today 16:380–383. [PubMed][CrossRef]
31. Ying S, Humbert M, Meng Q, Pfister R, Menz G, Gould HJ, Kay AB, Durham SR. 2001. Local expression of epsilon germline gene transcripts and RNA for the epsilon heavy chain of IgE in the bronchial mucosa in atopic and nonatopic asthma. J Allergy Clin Immunol 107:686–692. [PubMed]
32. Cameron L, Hamid Q, Wright E, Nakamura Y, Christodoulopoulos P, Muro S, Frenkiel S, Lavigne F, Durham S, Gould H. 2000. Local synthesis of epsilon germline gene transcripts, IL-4, and IL-13 in allergic nasal mucosa after ex vivo allergen exposure. J Allergy Clin Immunol 106:46–52. [PubMed]
33. Fawaz LM, Sharif-Askari E, Hajoui O, Soussi-Gounni A, Hamid Q, Mazer BD. 2007. Expression of IL-9 receptor alpha chain on human germinal center B cells modulates IgE secretion. J Allergy Clin Immunol 120:1208–1215. [PubMed][CrossRef]
34. Karagiannis SN, Bracher MG, Beavil RL, Beavil AJ, Hunt J, McCloskey N, Thompson RG, East N, Burke F, Sutton BJ, Dombrowicz D, Balkwill FR, Gould HJ. 2008. Role of IgE receptors in IgE antibody-dependent cytotoxicity and phagocytosis of ovarian tumor cells by human monocytic cells. Cancer Immunol Immunother 57:247–263. [PubMed][CrossRef]
35. Karagiannis SN, Bracher MG, Hunt J, McCloskey N, Beavil RL, Beavil AJ, Fear DJ, Thompson RG, East N, Burke F, Moore RJ, Dombrowicz DD, Balkwill FR, Gould HJ. 2007. IgE-antibody-dependent immunotherapy of solid tumors: cytotoxic and phagocytic mechanisms of eradication of ovarian cancer cells. J Immunol 179:2832–2843. [PubMed]
36. Ishizaka T, Conrad DH, Schulman ES, Sterk AR, Ishizaka K. 1983. Biochemical analysis of initial triggering events of IgE-mediated histamine release from human lung mast cells. J Immunol 130:2357–2362. [PubMed]
37. Dombrowicz D, Flamand V, Brigman KK, Koller BH, Kinet JP. 1993. Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor alpha chain gene. Cell 75:969–976. [PubMed]
38. Davey AM, Krise KM, Sheets ED, Heikal AA. 2008. Molecular perspective of antigen-mediated mast cell signaling. J Biol Chem 283:7117–7127. [PubMed][CrossRef]
39. MacNeil AJ, Yang YJ, Lin T-J. 2011. MAPK kinase 3 specifically regulates Fc epsilonRI-mediated IL-4 production by mast cells. J Immunol 187:3374–3382. [PubMed][CrossRef]
40. Medina-Tamayo J, Sanchez-Miranda E, Balleza-Tapia H, Ambriz X, Cid ME, Gonzalez-Espinosa D, Gutierrez AA, Gonzalez-Espinosa C. 2007. Super-oxidized solution inhibits IgE-antigen-induced degranulation and cytokine release in mast cells. Int. Immunopharmacol 7:1013–1024. [PubMed][CrossRef]
41. Nishida K, Yamasaki S, Ito Y, Kabu K, Hattori K, Tezuka T, Nishizumi H, Kitamura D, Goitsuka R, Geha RS, Yamamoto T, Yagi T, Hirano T. 2005. Fc{epsilon}RI-mediated mast cell degranulation requires calcium-independent microtubule-dependent translocation of granules to the plasma membrane. J Cell Biol 170:115–126. (Erratum, 171:177.) [PubMed][CrossRef]
42. Oka T, Sato K, Hori M, Ozaki H, Karaki H. 2002. FcepsilonRI cross-linking-induced actin assembly mediates calcium signalling in RBL-2H3 mast cells. Br J Pharmacol 136:837–846. [CrossRef]
43. Oettgen HC, Martin TR, Wynshaw-Boris A, Deng C, Drazen JM, Leder P. 1994. Active anaphylaxis in IgE-deficient mice. Nature 370:367–370. [PubMed][CrossRef]
44. Miyajima I, Dombrowicz D, Martin TR, Ravetch JV, Kinet JP, Galli SJ. 1997. Systemic anaphylaxis in the mouse can be mediated largely through IgG1 and Fc gammaRIII. Assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active or IgE- or IgG1-dependent passive anaphylaxis. J Clin Investig 99:901–914. [PubMed][CrossRef]
45. Jonsson F, Mancardi DA, Kita Y, Karasuyama H, Iannascoli B, Van Rooijen N, Shimizu T, Daeron M, Bruhns P. 2011. Mouse and human neutrophils induce anaphylaxis. J Clin Investig 121:1484–1496. [PubMed][CrossRef]
46. Daeron M. 1997. Fc receptor biology. Annu Rev Immunol 15:203–234. [PubMed][CrossRef]
47. Jonsson F, Mancardi DA, Zhao W, Kita Y, Iannascoli B, Khun H, van Rooijen N, Shimizu T, Schwartz LB, Daeron M, Bruhns P. 2012. Human FcgammaRIIA induces anaphylactic and allergic reactions. Blood 119:2533–2544. [PubMed][CrossRef]
48. Tsujimura Y, Obata K, Mukai K, Shindou H, Yoshida M, Nishikado H, Kawano Y, Minegishi Y, Shimizu T, Karasuyama H. 2008. Basophils play a pivotal role in immunoglobulin-G-mediated but not immunoglobulin-E-mediated systemic anaphylaxis. Immunity 28:581–589. [PubMed][CrossRef]
49. Finkelman FD, Urban JF, Jr. 2001. The other side of the coin: the protective role of the TH2 cytokines. J Allergy Clin Immunol 107:772–780. [PubMed][CrossRef]
50. Verwaerde C, Joseph M, Capron M, Pierce RJ, Damonneville M, Velge F, Auriault C, Capron A. 1987. Functional properties of a rat monoclonal IgE antibody specific for Schistosoma mansoni. J Immunol 138:4441–4446. [PubMed]
51. Capron M, Capron A. 1994. Immunoglobulin E and effector cells in schistosomiasis. Science 264:1876–1877. [PubMed]
52. Gounni AS, Lamkhioued B, Ochiai K, Tanaka Y, Delaporte E, Capron A, Kinet JP, Capron M. 1994. High-affinity IgE receptor on eosinophils is involved in defence against parasites. Nature 367:183–186. [PubMed][CrossRef]
53. Hagan P, Blumenthal UJ, Dunn D, Simpson AJ, Wilkins HA. 1991. Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium. Nature 349:243–245. [PubMed][CrossRef]
54. Dunne DW, Butterworth AE, Fulford AJ, Ouma JH, Sturrock RF. 1992. Human IgE responses to Schistosoma mansoni and resistance to reinfection. Mem Inst Oswaldo Cruz 87(Suppl 4) :99–103. [PubMed]
55. Gurish MF, Bryce PJ, Tao H, Kisselgof AB, Thornton EM, Miller HR, Friend DS, Oettgen HC. 2004. IgE enhances parasite clearance and regulates mast cell responses in mice infected with Trichinella spiralis. J Immunol 172:1139–1145. [PubMed]
56. Watanabe N, Bruschi F, Korenaga M. 2005. IgE: a question of protective immunity in Trichinella spiralis infection. Trends Parasitol 21:175–178. [PubMed][CrossRef]
57. Davis SD, Schaller J, Wedgwood RJ. 1966. Job's Syndrome. Recurrent, “cold,” staphylococcal abscesses. Lancet i:1013–1015. [PubMed]
58. Freeman AF, Holland SM. 2009. Clinical manifestations, etiology, and pathogenesis of the hyper-IgE syndromes. Pediatr Res 65:32R–37R. [PubMed][CrossRef]
59. Woellner C, Gertz EM, Schaffer AA, Lagos M, Perro M, Glocker EO, Pietrogrande MC, Cossu F, Franco JL, Matamoros N, Pietrucha B, Heropolitanska-Pliszka E, Yeganeh M, Moin M, Espanol T, Ehl S, Gennery AR, Abinun M, Breborowicz A, Niehues T, Kilic SS, Junker A, Turvey SE, Plebani A, Sanchez B, Garty BZ, Pignata C, Cancrini C, Litzman J, Sanal O, Baumann U, Bacchetta R, Hsu AP, Davis JN, Hammarstrom L, Davies EG, Eren E, Arkwright PD, Moilanen JS, Viemann D, Khan S, Marodi L, Cant AJ, Freeman AF, Puck JM, Holland SM, Grimbacher B. 2010. Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome. J Allergy Clin Immunol 125:424–432. [PubMed][CrossRef]
60. Su HC, Jing H, Zhang Q. 2011. DOCK8 deficiency. Ann NY Acad Sci 1246:26–33. [PubMed][CrossRef]
61. Engelhardt KR, McGhee S, Winkler S, Sassi A, Woellner C, Lopez-Herrera G, Chen A, Kim HS, Lloret MG, Schulze I, Ehl S, Thiel J, Pfeifer D, Veelken H, Niehues T, Siepermann K, Weinspach S, Reisli I, Keles S, Genel F, Kutukculer N, Camcioglu Y, Somer A, Karakoc-Aydiner E, Barlan I, Gennery A, Metin A, Degerliyurt A, Pietrogrande MC, Yeganeh M, Baz Z, Al-Tamemi S, Klein C, Puck JM, Holland SM, McCabe ER, Grimbacher B, Chatila TA. 2009. Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome. J Allergy Clin Immunol 124:1289–1302. [PubMed][CrossRef]
62. Freeman AF, Holland SM. 2010. Clinical manifestations of hyper IgE syndromes. Dis Markers 29:123–130. [PubMed][CrossRef]
63. Xiong H, Curotto de Lafaille MA, Lafaille JJ. 2012. What is unique about the IgE response? Adv Immunol 116:113–141. [PubMed][CrossRef]
64. Minegishi Y, Saito M, Tsuchiya S, Tsuge I, Takada H, Hara T, Kawamura N, Ariga T, Pasic S, Stojkovic O, Metin A, Karasuyama H. 2007. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 448:1058–1062. [PubMed][CrossRef]
65. He J, Shi J, Xu X, Zhang W, Wang Y, Chen X, Du Y, Zhu N, Zhang J, Wang Q, Yang J. 2012. STAT3 mutations correlated with hyper-IgE syndrome lead to blockage of IL-6/STAT3 signalling pathway. J Biosci 37:243–257. [PubMed]
66. Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM, Kanno Y, Spalding C, Elloumi HZ, Paulson ML, Davis J, Hsu A, Asher AI, O'shea J, Holland SM, Paul WE, Douek DC. 2008. Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452:773–776. [PubMed][CrossRef]
67. Dong C. 2008. TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol 8:337–348. [PubMed][CrossRef]
68. Renner ED, Rylaarsdam S, Anover-Sombke S, Rack AL, Reichenbach J, Carey JC, Zhu Q, Jansson AF, Barboza J, Schimke LF, Leppert MF, Getz MM, Seger RA, Hill HR, Belohradsky BH, Torgerson TR, Ochs HD. 2008. Novel signal transducer and activator of transcription 3 (STAT3) mutations, reduced T(H)17 cell numbers, and variably defective STAT3 phosphorylation in hyper-IgE syndrome. J Allergy Clin Immunol 122:181–187. [PubMed][CrossRef]
69. Erazo A, Kutchukhidze N, Leung M, Christ AP, Urban JF, Jr, Curotto de Lafaille MA, Lafaille JJ. 2007. Unique maturation program of the IgE response in vivo. Immunity 26:191–203. [PubMed][CrossRef]
70. Gevaert P, Nouri-Aria KT, Wu H, Harper CE, Takhar P, Fear DJ, Acke F, De Ruyck N, Banfield G, Kariyawasam HH, Bachert C, Durham SR, Gould HJ. 2013. Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps. Allergy 68:55–63. [PubMed][CrossRef]
71. Chularojanamontri L, Wimoolchart S, Tuchinda P, Kulthanan K, Kiewjoy N. 2009. Role of omalizumab in a patient with hyper-IgE syndrome and review of dermatologic manifestations. Asian Pac J Allergy Immunol 27:233–236. [PubMed]
72. Imani F, Proud D, Griffin DE. 1999. Measles virus infection synergizes with IL-4 in IgE class switching. J Immunol 162:1597–1602. [PubMed]
73. Rager KJ, Langland JO, Jacobs BL, Proud D, Marsh DG, Imani F. 1998. Activation of antiviral protein kinase leads to immunoglobulin E class switching in human B cells. J Virol 72:1171–1176. [PubMed]
74. Johnston SL, Pattemore PK, Sanderson G, Smith S, Lampe F, Josephs L, Symington P, O’Toole S, Myint SH, Tyrrell DA, et al. 1995. Community study of role of viral infections in exacerbations of asthma in 9–11 year old children. BMJ 310:1225–1229. [PubMed]
75. Nicholson KG, Kent J, Ireland DC. 1993. Respiratory viruses and exacerbations of asthma in adults. BMJ 307:982–986. [PubMed]
76. Murray CS, Poletti G, Kebadze T, Morris J, Woodcock A, Johnston SL, Custovic A. 2006. Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children. Thorax 61:376–382. [PubMed][CrossRef]
77. Green RM, Custovic A, Sanderson G, Hunter J, Johnston SL, Woodcock A. 2002. Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study. BMJ 324:763. [PubMed]
78. Zambrano JC, Carper HT, Rakes GP, Patrie J, Murphy DD, Platts-Mills TA, Hayden FG, Gwaltney JM, Jr, Hatley TK, Owens AM, Heymann PW. 2003. Experimental rhinovirus challenges in adults with mild asthma: response to infection in relation to IgE. J Allergy Clin Immunol 111:1008–1016. [PubMed]
79. Soto-Quiros M, Avila L, Platts-Mills TA, Hunt JF, Erdman DD, Carper H, Murphy DD, Odio S, James HR, Patrie JT, Hunt W, O'Rourke AK, Davis MD, Steinke JW, Lu X, Kennedy J, Heymann PW. 2012. High titers of IgE antibody to dust mite allergen and risk for wheezing among asthmatic children infected with rhinovirus. J Allergy Clin Immunol 129:1499–1505. [PubMed][CrossRef]
80. Corne JM, Marshall C, Smith S, Schreiber J, Sanderson G, Holgate ST, Johnston SL. 2002. Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study. Lancet 359:831–834. [PubMed][CrossRef]
81. Message SD, Laza-Stanca V, Mallia P, Parker HL, Zhu J, Kebadze T, Contoli M, Sanderson G, Kon OM, Papi A, Jeffery PK, Stanciu LA, Johnston SL. 2008. Rhinovirus-induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production. Proc Natl Acad Sci USA 105:13562–13567. [PubMed][CrossRef]
82. Paul WE, Zhu J. 2010. How are T(H)2-type immune responses initiated and amplified? Nat Rev Immunol 10:225–235. [PubMed][CrossRef]
83. Papadopoulos NG, Stanciu LA, Papi A, Holgate ST, Johnston SL. 2002. Rhinovirus-induced alterations on peripheral blood mononuclear cell phenotype and costimulatory molecule expression in normal and atopic asthmatic subjects. Clin Exp Allergy 32:537–542. [PubMed]
84. Perez-Yarza EG, Moreno A, Lazaro P, Mejias A, Ramilo O. 2007. The association between respiratory syncytial virus infection and the development of childhood asthma: a systematic review of the literature. Pediatr Infect Dis J 26:733–739. [PubMed][CrossRef]
85. Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B, Bjorksten B. 1995. Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis: a prospective cohort study with matched controls. Pediatrics 95:500–505. [PubMed]
86. Dakhama A, Lee YM, Ohnishi H, Jing X, Balhorn A, Takeda K, Gelfand EW. 2009. Virus-specific IgE enhances airway responsiveness on reinfection with respiratory syncytial virus in newborn mice. J Allergy Clin Immunol 123:138–145. [PubMed][CrossRef]
87. Chang TW. 2000. The pharmacological basis of anti-IgE therapy. Nat Biotechnol 18:157–162. [PubMed][CrossRef]
88. Adis International Ltd. 2002. Omalizumab: anti-IgE monoclonal antibody E25, E25, humanised anti-IgE MAb, IGE 025, monoclonal antibody E25, Olizumab, Xolair, rhuMAb-E25. BioDrugs 16:380–386. [PubMed]
89. Garman SC, Wurzburg BA, Tarchevskaya SS, Kinet J-P, Jardetzky TS. 2000. Structure of the Fc fragment of human IgE bound to its high-affinity receptor Fc[epsi]RI[alpha]. Nature 406:259–266. [PubMed][CrossRef]
90. Beck LA, Marcotte GV, MacGlashan D, Togias A, Saini S. 2004. Omalizumab-induced reductions in mast cell FcεRI expression and function. J Allergy Clin Immunol 114:527–530. [CrossRef]
91. Prussin C, Griffith DT, Boesel KM, Lin H, Foster B, Casale TB. 2003. Omalizumab treatment downregulates dendritic cell FcepsilonRI expression. J Allergy Clin Immunol 112:1147–1154. [PubMed][CrossRef]
92. MacGlashan DW, Bochner BS, Adelman DC, Jardieu PM, Togias A, McKenzie-White J, Sterbinsky SA, Hamilton RG, Lichtenstein LM. 1997. Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol 158:1438–1445. [PubMed]
93. Hunt J, Keeble AH, Dale RE, Corbett MK, Beavil RL, Levitt J, Swann MJ, Suhling K, Ameer-Beg S, Sutton BJ, Beavil AJ. 2012. A fluorescent biosensor reveals conformational changes in human immunoglobulin E Fc: implications for mechanisms of receptor binding, inhibition, and allergen recognition. J Biol Chem 287:17459–17470. [PubMed][CrossRef]
94. D’Amato G. 2006. Role of anti-IgE monoclonal antibody (omalizumab) in the treatment of bronchial asthma and allergic respiratory diseases. Eur J Pharmacol 533:302–307. [PubMed][CrossRef]
95. Leung DY, Sampson HA, Yunginger JW, Burks AW, Jr, Schneider LC, Wortel CH, Davis FM, Hyun JD, Shanahan WR, Jr. 2003. Effect of anti-IgE therapy in patients with peanut allergy. N Engl J Med 348:986–993.
96. van Neerven RJ, van Roomen CP, Thomas WR, de Boer M, Knol EF, Davis FM. 2001. Humanized anti-IgE mAb Hu-901 prevents the activation of allergen-specific T cells. Int Arch Allergy Immunol 124:400–402. [PubMed][CrossRef]
97. Poole JA, Meng J, Reff M, Spellman MC, Rosenwasser LJ. 2005. Anti-CD23 monoclonal antibody, lumiliximab, inhibited allergen-induced responses in antigen-presenting cells and T cells from atopic subjects. J Allergy Clin Immunol 116:780–788. [PubMed][CrossRef]
98. Shiung YY, Chiang CY, Chen JB, Wu PC, Hung AF, Lu DC, Pan RL, Chang TW. 2012. An anti-IgE monoclonal antibody that binds to IgE on CD23 but not on high-affinity IgE.Fc receptors. Immunobiology 217:676–683. [PubMed][CrossRef]
99. Chu SY, Horton HM, Pong E, Leung IW, Chen H, Nguyen DH, Bautista C, Muchhal US, Bernett MJ, Moore GL, Szymkowski DE, Desjarlais JR. 2012. Reduction of total IgE by targeted coengagement of IgE B-cell receptor and FcgammaRIIb with Fc-engineered antibody. J Allergy Clin Immunol 129:1102–1115. [PubMed][CrossRef]
100. Abdulla NE, Ninan MJ, Markowitz AB. 2012. Rituximab: current status as therapy for malignant and benign hematologic disorders. BioDrugs 26:71–82. [PubMed][CrossRef]
101. Simon D, Hosli S, Kostylina G, Yawalkar N, Simon HU. 2008. Anti-CD20 (rituximab) treatment improves atopic eczema. J Allergy Clin Immunol 121:122–128. [PubMed][CrossRef]
102. Arkwright PD. 2009. Anti-CD20 or anti-IgE therapy for severe chronic autoimmune urticaria. J Allergy Clin Immunol 123:510–511. (Author's reply, 123:511.) [PubMed][CrossRef]
103. Tanaka H, Nagai H, Maeda Y. 1998. Effect of anti-IL-4 and anti-IL-5 antibodies on allergic airway hyperresponsiveness in mice. Life Sci 62:PL169–PL174. [PubMed]
104. Steinke JW. 2004. Anti-interleukin-4 therapy. Immunol Allergy Clin N Am 24:599–614. [PubMed][CrossRef]
105. Piper E, Brightling C, Niven R, Oh C, Faggioni R, Poon K, She D, Kell C, May RD, Geba GP, Molfino NA. 2013. A phase 2 placebo-controlled study of tralokinumab in moderate-to-severe asthma. Eur Respir J 41:330–338. [PubMed][CrossRef]
106. Corren J, Lemanske RF, Hanania NA, Korenblat PE, Parsey MV, Arron JR, Harris JM, Scheerens H, Wu LC, Su Z, Mosesova S, Eisner MD, Bohen SP, Matthews JG. 2011. Lebrikizumab treatment in adults with asthma. N Engl J Med 365:1088–1098. [PubMed][CrossRef]
107. Lee JJ, McGarry MP, Farmer SC, Denzler KL, Larson KA, Carrigan PE, Brenneise IE, Horton MA, Haczku A, Gelfand EW, Leikauf GD, Lee NA. 1997. Interleukin-5 expression in the lung epithelium of transgenic mice leads to pulmonary changes pathognomonic of asthma. J Exp Med 185:2143–2156. [PubMed]
108. Stein ML, Villanueva JM, Buckmeier BK, Yamada Y, Filipovich AH, Assa'ad AH, Rothenberg ME. 2008. Anti-IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels. J Allergy Clin Immunol 121:1473–1483. [PubMed][CrossRef]
109. Adis International Ltd. 2008. Mepolizumab: 240563, anti-IL-5 monoclonal antibody - GlaxoSmithKline, anti-interleukin-5 monoclonal antibody - GlaxoSmithKline, SB 240563. Drugs R D 9:125–130. [PubMed]
110. Robinson DS. 2013. Mepolizumab treatment for asthma. Expert Opin Biol Ther 13:295–302. [PubMed][CrossRef]
111. Walsh GM. 2009. Reslizumab, a humanized anti-IL-5 mAb for the treatment of eosinophil-mediated inflammatory conditions. Curr Opin Mol Ther 11:329–336. [PubMed]
112. Busse WW, Katial R, Gossage D, Sari S, Wang B, Kolbeck R, Coyle AJ, Koike M, Spitalny GL, Kiener PA, Geba GP, Molfino NA. 2010. Safety profile, pharmacokinetics, and biologic activity of MEDI-563, an anti-IL-5 receptor alpha antibody, in a phase I study of subjects with mild asthma. J Allergy Clin Immunol 125:1237–1244. [PubMed][CrossRef]
113. Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, Damschroder MM, Reed JL, Woods R, Dall’acqua WW, Stephens GL, Erjefalt JS, Bjermer L, Humbles AA, Gossage D, Wu H, Kiener PA, Spitalny GL, Mackay CR, Molfino NA, Coyle AJ. 2010. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol 125:1344–1353. [PubMed][CrossRef]
114. Kearley J, Erjefalt JS, Andersson C, Benjamin E, Jones CP, Robichaud A, Pegorier S, Brewah Y, Burwell TJ, Bjermer L, Kiener PA, Kolbeck R, Lloyd CM, Coyle AJ, Humbles AA. 2011. IL-9 governs allergen-induced mast cell numbers in the lung and chronic remodeling of the airways. Am J Respir Crit Care Med 183:865–875. [PubMed][CrossRef]
115. Parker JM, Oh CK, LaForce C, Miller SD, Pearlman DS, Le C, Robbie GJ, White WI, White B, Molfino NA. 2011. Safety profile and clinical activity of multiple subcutaneous doses of MEDI-528, a humanized anti-interleukin-9 monoclonal antibody, in two randomized phase 2a studies in subjects with asthma. BMC Pulm Med 11:14. [PubMed][CrossRef]
116. Brightling C, Berry M, Amrani Y. 2008. Targeting TNF-alpha: a novel therapeutic approach for asthma. J Allergy Clin Immunol 121:5–10. [PubMed][CrossRef]
117. Wenzel SE, Barnes PJ, Bleecker ER, Bousquet J, Busse W, Dahlen SE, Holgate ST, Meyers DA, Rabe KF, Antczak A, Baker J, Horvath I, Mark Z, Bernstein D, Kerwin E, Schlenker-Herceg R, Lo KH, Watt R, Barnathan ES, Chanez P. 2009. A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma. Am J Respir Crit Care Med 179:549–558. [PubMed][CrossRef]
118. Ivanciuc O, Schein CH, Braun W. 2002. Data mining of sequences and 3D structures of allergenic proteins. Bioinformatics 18:1358–1364. [PubMed]
119. Reisinger J, Horak F, Pauli G, van Hage M, Cromwell O, Konig F, Valenta R, Niederberger V. 2005. Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. J Allergy Clin Immunol 116:347–354. [PubMed][CrossRef]
120. Niederberger V, Horak F, Vrtala S, Spitzauer S, Krauth MT, Valent P, Reisinger J, Pelzmann M, Hayek B, Kronqvist M, Gafvelin G, Gronlund H, Purohit A, Suck R, Fiebig H, Cromwell O, Pauli G, van Hage-Hamsten M, Valenta R. 2004. Vaccination with genetically engineered allergens prevents progression of allergic disease. Proc Natl Acad Sci USA 101(Suppl 2) :14677–14682. [PubMed][CrossRef]
121. Bordas-Le Floch V, Bussieres L, Airouche S, Lautrette A, Bouley J, Berjont N, Horiot S, Huet A, Jain K, Lemoine P, Chabre H, Batard T, Mascarell L, Baron-Bodo V, Tourdot S, Nony E, Moingeon P. 2012. Expression and characterization of natural-like recombinant Der p 2 for sublingual immunotherapy. Int Arch Allergy Immunol 158:157–167. [PubMed][CrossRef]
122. Chruszcz M, Pomes A, Glesner J, Vailes LD, Osinski T, Porebski PJ, Majorek KA, Heymann PW, Platts-Mills TAE, Minor W, Chapman MD. 2012. Molecular determinants for antibody binding on group 1 house dust mite allergens. J Biol Chem 287:7388–7398. [PubMed][CrossRef]
123. Marsh DG, Lichtenstein LM, Campbell DH. 1970. Studies on “allergoids” prepared from naturally occurring allergens. I. Assay of allergenicity and antigenicity of formalinized rye group I component. Immunology 18:705–722. [PubMed]
124. Ferrari E, Breda D, Longhi R, Vangelista L, Nakaie CR, Elviri L, Casali E, Pertinhez TA, Spisni A, Burastero SE. 2012. In search of a vaccine for mouse allergy: significant reduction of Mus m 1 allergenicity by structure-guided single-point mutations. Int Arch Allergy Immunol 157:226–237. [PubMed][CrossRef]
125. Valenta R, Linhart B, Swoboda I, Niederberger V. 2011. Recombinant allergens for allergen-specific immunotherapy: 10 years anniversary of immunotherapy with recombinant allergens. Allergy 66:775–783. [PubMed][CrossRef]
126. Canonica GW, Bousquet J, Casale T, Lockey RF, Baena-Cagnani CE, Pawankar R, Potter PC, Bousquet PJ, Cox LS, Durham SR, Nelson HS, Passalacqua G, Ryan DP, Brozek JL, Compalati E, Dahl R, Delgado L, van Wijk RG, Gower RG, Ledford DK, Filho NR, Valovirta EJ, Yusuf OM, Zuberbier T, Akhanda W, Almarales RC, Ansotegui I, Bonifazi F, Ceuppens J, Chivato T, Dimova D, Dumitrascu D, Fontana L, Katelaris CH, Kaulsay R, Kuna P, Larenas-Linnemann D, Manoussakis M, Nekam K, Nunes C, O’Hehir R, Olaguibel JM, Onder NB, Park JW, Priftanji A, Puy R, Sarmiento L, Scadding G, Schmid-Grendelmeier P, Seberova E, Sepiashvili R, Sole D, Togias A, Tomino C, Toskala E, Van Beever H, Vieths S. 2009. Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009. Allergy 64(Suppl 91) :1–59. [PubMed][CrossRef]
127. Shamji MH, Ljorring C, Francis JN, Calderon MA, Larche M, Kimber I, Frew AJ, Ipsen H, Lund K, Wurtzen PA, Durham SR. 2012. Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy. Allergy 67:217–226. [PubMed][CrossRef]
128. James LK, Bowen H, Calvert RA, Dodev TS, Shamji MH, Beavil AJ, McDonnell JM, Durham SR, Gould HJ. 2012. Allergen specificity of IgG(4)-expressing B cells in patients with grass pollen allergy undergoing immunotherapy. J Allergy Clin Immunol 130:663–670. [PubMed][CrossRef]
129. Pilette C, Nouri-Aria KT, Jacobson MR, Wilcock LK, Detry B, Walker SM, Francis JN, Durham SR. 2007. Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-beta expression. J Immunol 178:4658–4666. [PubMed]
130. Satoguina JS, Weyand E, Larbi J, Hoerauf A. 2005. T regulatory-1 cells induce IgG4 production by B cells: role of IL-10. J Immunol 174:4718–4726. [PubMed]
131. Wood N, Bourque K, Donaldson DD, Collins M, Vercelli D, Goldman SJ, Kasaian MT. 2004. IL-21 effects on human IgE production in response to IL-4 or IL-13. Cell Immunol 231:133–145. [PubMed][CrossRef]
132. van der Neut Kolfschoten M, Schuurman J, Losen M, Bleeker WK, Martinez-Martinez P, Vermeulen E, den Bleker TH, Wiegman L, Vink T, Aarden LA, De Baets MH, van de Winkel JG, Aalberse RC, Parren PW. 2007. Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. Science 317:1554–1557. [PubMed][CrossRef]
133. Passalacqua G, Albano M, Riccio A, Fregonese L, Puccinelli P, Parmiani S, Canonica GW. 1999. Clinical and immunologic effects of a rush sublingual immunotherapy to Parietaria species: a double-blind, placebo-controlled trial. J Allergy Clin Immunol 104:964–968. [PubMed]
134. Savilahti EM, Rantanen V, Lin JS, Karinen S, Saarinen KM, Goldis M, Makela MJ, Hautaniemi S, Savilahti E, Sampson HA. 2010. Early recovery from cow's milk allergy is associated with decreasing IgE and increasing IgG4 binding to cow's milk epitopes. J Allergy Clin Immunol 125:1315–1321. [PubMed][CrossRef]
135. Savilahti EM, Saarinen KM, Savilahti E. 2010. Duration of clinical reactivity in cow's milk allergy is associated with levels of specific immunoglobulin G4 and immunoglobulin A antibodies to beta-lactoglobulin. Clin Exp Allergy 40:251–256. [PubMed][CrossRef]
136. Harada K, Shimoda S, Kimura Y, Sato Y, Ikeda H, Igarashi S, Ren XS, Sato H, Nakanuma Y. 2012. Significance of immunoglobulin G4 (IgG4)-positive cells in extrahepatic cholangiocarcinoma: molecular mechanism of IgG4 reaction in cancer tissue. Hepatology 56:157–164. [PubMed][CrossRef]
137. Karagiannis P, Gilbert AE, Josephs DH, Ali N, Dodev T, Saul L, Correa I, Roberts L, Beddowes E, Koers A, Hobbs C, Ferreira S, Geh JL, Healy C, Harries M, Acland KM, Blower PJ, Mitchell T, Fear DJ, Spicer JF, Lacy KE, Nestle FO, Karagiannis SN. 2013. IgG4 subclass antibodies impair antitumor immunity in melanoma. J Clin Investig 123:1457–1474. [PubMed][CrossRef]
138. Karagiannis SN, Josephs DH, Karagiannis P, Gilbert AE, Saul L, Rudman SM, Dodev T, Koers A, Blower PJ, Corrigan C, Beavil AJ, Spicer JF, Nestle FO, Gould HJ. 2012. Recombinant IgE antibodies for passive immunotherapy of solid tumours: from concept towards clinical application. Cancer Immunol Immunother 61:1547–1564. [PubMed][CrossRef]
139. Karagiannis SN, Wang Q, East N, Burke F, Riffard S, Bracher MG, Thompson RG, Durham SR, Schwartz LB, Balkwill FR, Gould HJ. 2003. Activity of human monocytes in IgE antibody-dependent surveillance and killing of ovarian tumor cells. Eur J Immunol 33:1030–1040. [PubMed][CrossRef]
140. Gould HJ, Mackay GA, Karagiannis SN, O’Toole CM, Marsh PJ, Daniel BE, Coney LR, Zurawski VR, Jr, Joseph M, Capron M, Gilbert M, Murphy GF, Korngold R. 1999. Comparison of IgE and IgG antibody-dependent cytotoxicity in vitro and in a SCID mouse xenograft model of ovarian carcinoma. Eur J Immunol 29:3527–3537. [PubMed][CrossRef]
141. Karagiannis SN, Nestle FO, Gould HJ. 2010. IgE interacts with potent effector cells against tumors: ADCC and ADCP, p 185–213. In Penichet ML, Jensen-Jarolim E (ed), Cancer and IgE. Humana Press, Springer, New York, NY.
142. Karagiannis P, Singer J, Hunt J, Gan SK, Rudman SM, Mechtcheriakova D, Knittelfelder R, Daniels TR, Hobson PS, Beavil AJ, Spicer J, Nestle FO, Penichet ML, Gould HJ, Jensen-Jarolim E, Karagiannis SN. 2009. Characterisation of an engineered trastuzumab IgE antibody and effector cell mechanisms targeting HER2/neu-positive tumour cells. Cancer Immunol Immunother 58:915–930. [PubMed][CrossRef]
143. Rudman SM, Josephs DH, Cambrook H, Karagiannis P, Gilbert AE, Dodev T, Hunt J, Koers A, Montes A, Taams L, Canevari S, Figini M, Blower PJ, Beavil AJ, Nicodemus CF, Corrigan C, Kaye SB, Nestle FO, Gould HJ, Spicer JF, Karagiannis SN. 2011. Harnessing engineered antibodies of the IgE class to combat malignancy: initial assessment of FcεRI-mediated basophil activation by a tumour-specific IgE antibody to evaluate the risk of type I hypersensitivity. Clin Exp Allergy 41:1400–1413. [PubMed][CrossRef]
144. Jensen-Jarolim E, Singer J. 2011. Why could passive immunoglobulin E antibody therapy be safe in clinical oncology? Clin Exp Allergy 41:1337–1340. [PubMed][CrossRef]
145. Sutton BJ, Beavil RL, Beavil AJ. 2000. Inhibition of IgE-receptor interactions. Br Med Bull 56:1004–1018. [PubMed]
146. Nigro EA, Brini AT, Soprana E, Ambrosi A, Dombrowicz D, Siccardi AG, Vangelista L. 2009. Antitumor IgE adjuvanticity: key role of Fc epsilon RI. J Immunol 183:4530–4536. [PubMed][CrossRef]
147. Teng MW, Kershaw MH, Jackson JT, Smyth MJ, Darcy PK. 2006. Adoptive transfer of chimeric FcepsilonRI gene-modified human T cells for cancer immunotherapy. Hum Gene Ther 17:1134–1143. [PubMed][CrossRef]
148. Kershaw MH, Darcy PK, Trapani JA, MacGregor D, Smyth MJ. 1998. Tumor-specific IgE-mediated inhibition of human colorectal carcinoma xenograft growth. Oncol Res 10:133–142. [PubMed]
149. Teo PZ, Utz PJ, Mollick JA. 2012. Using the allergic immune system to target cancer: activity of IgE antibodies specific for human CD20 and MUC1. Cancer Immunol Immunother 61:2295–2309. [PubMed][CrossRef]
150. Spillner E, Plum M, Blank S, Miehe M, Singer J, Braren I. 2012. Recombinant IgE antibody engineering to target EGFR. Cancer Immunol Immunother 61:1565–1573. [PubMed][CrossRef]
151. Daniels TR, Leuchter RK, Quintero R, Helguera G, Rodriguez JA, Martinez-Maza O, Schultes BC, Nicodemus CF, Penichet ML. 2012. Targeting HER2/neu with a fully human IgE to harness the allergic reaction against cancer cells. Cancer Immunol Immunother 61:991–1003. [PubMed][CrossRef]
152. Riemer AB, Untersmayr E, Knittelfelder R, Duschl A, Pehamberger H, Zielinski CC, Scheiner O, Jensen-Jarolim E. 2007. Active induction of tumor-specific IgE antibodies by oral mimotope vaccination. Cancer Res 67:3406–3411. [PubMed][CrossRef]
153. Knittelfelder R, Riemer AB, Jensen-Jarolim E. 2009. Mimotope vaccination--from allergy to cancer. Expert Opin Biol Ther 9:493–506. [PubMed][CrossRef]
154. Jensen-Jarolim E, Achatz G, Turner MC, Karagiannis S, Legrand F, Capron M, Penichet ML, Rodriguez JA, Siccardi AG, Vangelista L, Riemer AB, Gould H. 2008. AllergoOncology: the role of IgE-mediated allergy in cancer. Allergy 63:1255–1266. [PubMed][CrossRef]
155. Jensen-Jarolim E, Pawelec G. 2012. The nascent field of AllergoOncology. Cancer Immunol Immunother 61:1355–1357. [PubMed][CrossRef]
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/content/journal/microbiolspec/10.1128/microbiolspec.AID-0006-2012
2013-10-25
2019-10-20

Abstract:

The pathogenic role of immunoglobulin E (IgE) antibodies in triggering and maintaining allergic inflammation in response to allergens is due to the binding of multivalent allergens to allergen-specific IgEs on sensitized effector cells. These interactions trigger effector cell activation, resulting in release of potent inflammatory mediators, recruitment of inflammatory cells, antigen presentation, and production of allergen-specific antibody responses. Since its discovery in the 1960s, the central role of IgE in allergic disease has been intensively studied, placing IgE and its functions at the heart of therapeutic efforts for the treatment of allergies. Here, we provide an overview of the nature, roles, and significance of IgE antibodies in allergic diseases, infections, and inflammation and the utility of antibodies as therapies. We place special emphasis on allergen-IgE-Fcε receptor complexes in the context of allergic and inflammatory diseases and describe strategies, including monoclonal antibodies, aimed at interrupting these complexes. Of clinical significance, one antibody, omalizumab, is presently in clinical use and works by preventing formation of IgE-Fcε receptor interactions. Active immunotherapy approaches with allergens and allergen derivatives have also demonstrated clinical benefits for patients with allergic diseases. These treatments are strongly associated with serum increases of IgE-neutralizing antibodies and feature a notable redirection of humoral responses towards production of antibodies of the IgG4 subclass in patients receiving immunotherapies. Lastly, we provide a new perspective on the rise of recombinant antibodies of the IgE class recognizing tumor-associated antigens, and we discuss the potential utility of tumor antigen-specific IgE antibodies to direct potent IgE-driven immune responses against tumors.

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Immunoglobulin E and Allergy: Antibodies in Immune Inflammation and Treatment
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Citation: Karagiannis S, Karagiannis P, Josephs D, Saul L, Gilbert A, Upton N, Gould H. 2013. Immunoglobulin e and allergy: antibodies in immune inflammation and treatment. microbiolspec 1(1): doi:10.1128/microbiolspec.AID-0006-2012
/content/microbiolspec/10.1128/microbiolspec.AID-0006-2012.fig1
FIGURE 1

Omalizumab blocks IgE-mediated mast cell activation. The allergic response mediated by multivalent allergen-IgE-FcεRI complex formation on the surface of mast cells triggers cross-linking of FcεRI, leading to downstream signaling events potentiated by the β and γ chains (left). These entail phosphorylation (P) by Src kinases and cellular activation through RhoGTPases and mitogen-activated protein kinase pathways, leading to mast cell degranulation and the rapid release of a range of vasoactive amines (e.g., histamine), prostaglandins, leukotrienes, cytokines, and chemokines, inducing and maintaining allergic inflammatory responses. Omalizumab, a humanized IgG1 monoclonal antibody that recognizes an epitope in the Cε3 region of IgE, can block the binding of circulating IgE to FcεRI, sequestering free and allergen-bound IgE (right). These interactions prevent allergen-IgE-FcεRI complex formation on the surface of mast cells and interfere with the signaling cascades that trigger degranulation and the onset of IgE-mediated allergic inflammatory cascades. Syk, spleen tyrosine kinase; AKT, Ak strain thymoma serine/threonine-specific protein kinase; ERK, extracellular signal-regulated kinase; JNK, Jun N-terminal protein kinase; P, phosphorylation. doi:10.1128/microbiolspec.AID-0006-2012.f1

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FIGURE 1

Omalizumab blocks IgE-mediated mast cell activation. The allergic response mediated by multivalent allergen-IgE-FcεRI complex formation on the surface of mast cells triggers cross-linking of FcεRI, leading to downstream signaling events potentiated by the β and γ chains (left). These entail phosphorylation (P) by Src kinases and cellular activation through RhoGTPases and mitogen-activated protein kinase pathways, leading to mast cell degranulation and the rapid release of a range of vasoactive amines (e.g., histamine), prostaglandins, leukotrienes, cytokines, and chemokines, inducing and maintaining allergic inflammatory responses. Omalizumab, a humanized IgG1 monoclonal antibody that recognizes an epitope in the Cε3 region of IgE, can block the binding of circulating IgE to FcεRI, sequestering free and allergen-bound IgE (right). These interactions prevent allergen-IgE-FcεRI complex formation on the surface of mast cells and interfere with the signaling cascades that trigger degranulation and the onset of IgE-mediated allergic inflammatory cascades. Syk, spleen tyrosine kinase; AKT, Ak strain thymoma serine/threonine-specific protein kinase; ERK, extracellular signal-regulated kinase; JNK, Jun N-terminal protein kinase; P, phosphorylation. doi:10.1128/microbiolspec.AID-0006-2012.f1

Source: microbiolspec October 2013 vol. 1 no. 1 doi:10.1128/microbiolspec.AID-0006-2012
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FIGURE 2

IgG4 antibodies induced by allergen immunotherapies modulate IgE-mediated activation of effector cells. The allergic response mediated by multivalent allergen-IgE FcεRI complex assembly and downstream signaling events leading to release of inflammatory mediators (left) may be blocked by adaptive immune responses triggered in response to SIT with recombinant antigens. IgG4 antibodies, induced following SIT, could compete with IgE for binding to allergens and prevent the formation of allergen-IgE-FcεRI complexes on the surface of effector cells, blocking effector functions such as degranulation (right). Syk, spleen tyrosine kinase; AKT, Ak strain thymoma serine/threonine-specific protein kinase; ERK, extracellular signal-regulated kinase; JNK, Jun N-terminal protein kinase; P, phosphorylation. doi:10.1128/microbiolspec.AID-0006-2012.f2

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FIGURE 2

IgG4 antibodies induced by allergen immunotherapies modulate IgE-mediated activation of effector cells. The allergic response mediated by multivalent allergen-IgE FcεRI complex assembly and downstream signaling events leading to release of inflammatory mediators (left) may be blocked by adaptive immune responses triggered in response to SIT with recombinant antigens. IgG4 antibodies, induced following SIT, could compete with IgE for binding to allergens and prevent the formation of allergen-IgE-FcεRI complexes on the surface of effector cells, blocking effector functions such as degranulation (right). Syk, spleen tyrosine kinase; AKT, Ak strain thymoma serine/threonine-specific protein kinase; ERK, extracellular signal-regulated kinase; JNK, Jun N-terminal protein kinase; P, phosphorylation. doi:10.1128/microbiolspec.AID-0006-2012.f2

Source: microbiolspec October 2013 vol. 1 no. 1 doi:10.1128/microbiolspec.AID-0006-2012
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Immunoglobulin E and Allergy: Antibodies in Immune Inflammation and Treatment
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Citation: Karagiannis S, Karagiannis P, Josephs D, Saul L, Gilbert A, Upton N, Gould H. 2013. Immunoglobulin e and allergy: antibodies in immune inflammation and treatment. microbiolspec 1(1): doi:10.1128/microbiolspec.AID-0006-2012
/content/microbiolspec/10.1128/microbiolspec.AID-0006-2012.T1
TABLE 1

Interactions of omalizumab with IgE, the resulting mechanisms of action, and clinical effects of treatment in patients with allergies

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TABLE 1

Interactions of omalizumab with IgE, the resulting mechanisms of action, and clinical effects of treatment in patients with allergies

Source: microbiolspec October 2013 vol. 1 no. 1 doi:10.1128/microbiolspec.AID-0006-2012
/content/microbiolspec/10.1128/microbiolspec.AID-0006-2012.T2
TABLE 2

Active phase II, III, and IV interventional clinical studies for antibody immunotherapies of allergic diseases in 2012

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TABLE 2

Active phase II, III, and IV interventional clinical studies for antibody immunotherapies of allergic diseases in 2012

Source: microbiolspec October 2013 vol. 1 no. 1 doi:10.1128/microbiolspec.AID-0006-2012

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