Structural basis of omalizumab therapy and omalizumab-mediated IgE exchange

Nature Communications

Volumn 7, Issue , 2016, Pages

  Pennington, Luke F ^a   Tarchevskaya, Svetlana ^a   Brigger, Daniel ^b,c   Sathiyamoorthy, Karthik ^a   Graham, Michelle T ^a   Nadeau, Kari Christine ^a   Eggel, Alexander ^b,c   Jardetzky, Theodore S ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF BERN   (Switzerland)

^c UNIVERSITY OF BERN   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN E; IMMUNOGLOBULIN E RECEPTOR; IMMUNOGLOBULIN F(AB) FRAGMENT; IMMUNOGLOBULIN FC FRAGMENT; OMALIZUMAB; ANTIALLERGIC AGENT;

ANTIBODY; CELLS AND CELL COMPONENTS; CRYSTAL STRUCTURE; DRUG; INHIBITION; PROBE;

ARTICLE; BASOPHIL; BINDING AFFINITY; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; CRYSTAL STRUCTURE; DISSOCIATION; DRUG BINDING; DRUG STRUCTURE; HUMAN; HUMAN CELL; HYPERSENSITIVITY; REGULATORY MECHANISM; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL LINE; CHEMISTRY; DRUG EFFECT; DRUG POTENTIATION; GENETICS; MUTATION; PROTEIN CONFORMATION;

ANIMALS; ANTI-ALLERGIC AGENTS; BASOPHILS; CELL LINE; DRUG SYNERGISM; HUMANS; IMMUNOGLOBULIN E; MUTATION; OMALIZUMAB; PROTEIN CONFORMATION; RECEPTORS, IGE;

EID: 84970969698     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms11610     Document Type: Article

References (55)

1. Gould, H. J. & Sutton, B. J. IgE in allergy and asthma today. Nat. Rev. Immunol. 8, 205-217 (2008).
2. Okada, H., Kuhn, C., Feillet, H. & Bach, J. F. The hygiene hypothesis for autoimmune and allergic diseases: An update. Clin. Exp. Immunol. 160, 1-9 (2010).
3. Galli, S. J. & Tsai, M. IgE and mast cells in allergic disease. Nat. Med. 18, 693-704 (2012).
4. Blank, U., Ra, C. S. & Kinet, J. P. Characterization of truncated alpha chain products from human, rat, and mouse high affinity receptor for immunoglobulin E. J. Biol. Chem. 266, 2639-2646 (1991).
5. Garman, S. C., Wurzburg, B. A., Tarchevskaya, S. S., Kinet, J. P. & Jardetzky, T. S. Structure of the Fc fragment of human IgE bound to its high-Affinity receptor Fc epsilonRI alpha. Nature 406, 259-266 (2000).
6. Yu, P., Kosco-Vilbois, M., Richards, M., Kohler, G. & Lamers, M. C. Negative feedback regulation of IgE synthesis by murine CD23. Nature 369, 753-756 (1994).
7. Getahun, A., Hjelm, F. & Heyman, B. IgE enhances antibody and T cell responses in vivo via CD23(+) B cells. J. Immunol. 175, 1473-1482 (2005).
8. Cooper, A. M. et al. Soluble CD23 controls IgE synthesis and homeostasis in human B cells. J. Immunol. 188, 3199-3207 (2012).
9. Heyman, B., Liu, T. M. & Gustavsson, S. In-vivo enhancement of the specific antibody-response via the low-Affinity receptor for IgE. Eur. J. Immunol. 23, 1739-1742 (1993).
10. Chretien, I. et al. A monoclonal anti-IgE antibody against an epitope (amino acids 367-376) in the CH3 domain inhibits IgE binding to the low affinity IgE receptor (CD23). J. Immunol. 141, 3128-3134 (1988).
11. Sherr, E., Macy, E., Kimata, H., Gilly, M. & Saxon, A. Binding the low affinity Fc epsilon R on B cells suppresses ongoing human IgE synthesis. J. Immunol. 142, 481-489 (1989).
12. Bonnefoy, J. Y. et al. Regulation of IgE synthesis by CD23/CD21 interaction. Int. Arch. Allergy Immunol. 107, 40-42 (1995).
13. Holdom, M. D. et al. Conformational changes in IgE contribute to its uniquely slow dissociation rate from receptor FcvarepsilonRI. Nat. Struct. Mol. Biol. 18, 571-576 (2011).
14. Dhaliwal, B. et al. Crystal structure of IgE bound to its B-cell receptor CD23 reveals a mechanism of reciprocal allosteric inhibition with high affinity receptor Fc{varepsilon}RI. Proc. Natl Acad. Sci. USA 109, 12686-12691 (2012).
15. Wurzburg, B. A., Garman, S. C. & Jardetzky, T. S. Structure of the human IgE-Fc C epsilon 3-C epsilon 4 reveals conformational flexibility in the antibody effector domains. Immunity 13, 375-385 (2000).
16. Busse, W. et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J. Allergy Clin. Immunol. 108, 184-190 (2001).
17. Braunstahl, G. J. et al. The eXpeRience registry: The real-world effectiveness of omalizumab in allergic asthma. Resp. Med. 107, 1141-1151 (2013).
18. Saini, S. S. et al. Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: A randomized, placebo-controlled study. J. Invest. Dermatol. 135, 925 (2015).
19. Nadeau, K. C., Kohli, A., Iyengar, S., DeKruyff, R. H. & Umetsu, D. T. Oral immunotherapy and anti-IgE antibody-Adjunctive treatment for food allergy. Immunol. Allergy Clin. North Am. 32, 111-133 (2012).
20. Lieberman, J. A. & Chehade, M. Use of omalizumab in the treatment of food allergy and anaphylaxis. Curr. Allergy Asthma Rep. 13, 78-84 (2013).
21. Lowe, P. J., Tannenbaum, S., Gautier, A. & Jimenez, P. Relationship between omalizumab pharmacokinetics, IgE pharmacodynamics and symptoms in patients with severe persistent allergic (IgE-mediated) asthma. Br. J. Clin. Pharmacol. 68, 61-76 (2009).
22. Baumann, M. J., Eggel, A., Amstutz, P., Stadler, B. M. & Vogel, M. DARPins against a functional IgE epitope. Immunol. Lett. 133, 78-84 (2010).
23. Kim, B. et al. Accelerated disassembly of IgE-receptor complexes by a disruptive macromolecular inhibitor. Nature 491, 613-617 (2012).
24. Presta, L. & Shields, R. in Lung Biology in Health and Disease. Vol. 164 (eds Fick, R. B. Jr. & Jardieu, P. M.) (Marcel Dekker, 2002).
25. Eggel, A. et al. Accelerated dissociation of IgE-FceRI complexes by disruptive inhibitors actively desensitizes allergic effector cells. J. Allergy Clin. Immunol. 133, 1709-1719 (2014).
26. Prussin, C. et al. Omalizumab treatment downregulates dendritic cell FcepsilonRI expression. J. Allergy Clin. Immunol. 112, 1147-1154 (2003).
27. MacGlashan, Jr D. W. et al. 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 (1997).
28. Zaidi, A. K., Saini, S. S. & Macglashan, Jr. D. W. Regulation of Syk kinase and FcRbeta expression in human basophils during treatment with omalizumab. J. Allergy Clin. Immunol. 125, 902-908 e907 (2010).
29. MacGlashan, Jr D. W., Savage, J. H., Wood, R. A. & Saini, S. S. Suppression of the basophil response to allergen during treatment with omalizumab is dependent on 2 competing factors. J. Allergy Clin. Immunol. 130, 1130-1135 (2012).
30. Macglashan, Jr D. W. & Saini, S. S. Omalizumab increases the intrinsic sensitivity of human basophils to IgE-mediated stimulation. J. Allergy Clin. Immunol. 132, 906-911 (2013).
31. Aubry, J. P., Pochon, S., Graber, P., Jansen, K. U. & Bonnefoy, J. Y. CD21 is a ligand for CD23 and regulates IgE production. Nature 358, 505-507 (1992).
32. Fellmann, M., Buschor, P., Röthlisberger, S., Zellweger, F. & Vogel, M. High affinity targeting of CD23 inhibits IgE synthesis in human B cells. Immun. Inflamm. Dis. 3, 339-349 (2015).
33. Wurzburg, B. A. et al. An engineered disulfide bond reversibly traps the IgE-Fc3-4 in a closed, nonreceptor binding conformation. J. Biol. Chem. 287, 36251-36257 (2012).
34. Jensen, R. K. et al. Structure of the omalizumab Fab. Acta Crystallogr. F Struct. Biol. Commun. 71, 419-426 (2015).
35. Wright, J. D. et al. Structural and physical basis for Anti-IgE therapy. Sci. Rep. 5, 11581 (2015).
36. Krissinel, E. & Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774-797 (2007).
37. Presta, L. et al. The binding site on human immunoglobulin E for its high affinity receptor. J. Biol. Chem. 269, 26368-26373 (1994).
38. Wurzburg, B. A. & Jardetzky, T. S. Conformational flexibility in immunoglobulin E-Fc 3-4 revealed in multiple crystal forms. J. Mol. Biol. 393, 176-190 (2009).
39. Cohen, E. S. et al. A novel IgE-neutralizing antibody for the treatment of severe uncontrolled asthma. MAbs 6, 756-764 (2014).
40. Pettersen, E. F. et al. UCSF Chimera-A visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605-1612 (2004).
41. Nettleton, M. Y. & Kochan, J. P. Role of glycosylation sites in the IgE Fc molecule. Int. Arch. Allergy Immunol. 107, 328-329 (1995).
42. Shade, K. T. et al. A single glycan on IgE is indispensable for initiation of anaphylaxis. J. Exp. Med. 212, 457-467 (2015).
43. Arm, J. P. et al. Pharmacokinetics, pharmacodynamics and safety of QGE031 (ligelizumab), a novel high-Affinity anti-IgE antibody, in atopic subjects. Clin. Exp. Allergy 44, 1371-1385 (2014).
44. Beck, L. A., Marcotte, G. V., MacGlashan, D., Togias, A. & Saini, S. Omalizumab-induced reductions in mast cell Fc epsilon RI expression and function. J. Allergy Clin. Immunol. 114, 527-530 (2004).
45. MacGlashan, Jr D. Facilitated dissociation of IgE versus cell replacement. J. Allergy Clin. Immunol. 135, 294-295 (2015).
46. Korn, S. et al. Monitoring free serum IgE in severe asthma patients treated with omalizumab. Respir Med. 106, 1494-1500 (2012).
47. Torigoe, C., Inman, J. K. & Metzger, H. An unusual mechanism for ligand antagonism. Science 281, 568-572 (1998).
48. Cheng, L. E., Hartmann, K., Roers, A., Krummel, M. F. & Locksley, R. M. Perivascular mast cells dynamically probe cutaneous blood vessels to capture immunoglobulin E. Immunity 38, 166-175 (2013).
49. Wei, X. et al. Antibody neutralization and escape by HIV-1. Nature 422, 307-312 (2003).
50. Chan, Y. C. et al. "Auto-Anti-IgE": naturally occurring IgG anti-IgE antibodies may inhibit allergen-induced basophil activation. J. Allergy Clin. Immunol. 134, 1394-+ (2014).
51. Kim, B., Tarchevskaya, S. S., Eggel, A., Vogel, M. & Jardetzky, T. S. A time-resolved fluorescence resonance energy transfer assay suitable for high-Throughput screening for inhibitors of immunoglobulin E-receptor interactions. Anal. Biochem. 431, 84-89 (2012).
52. Otwinowski, Z. & Minor, W. in Methods in Enzymology: Macromolecular Crystallography, part A (eds Carter, C. W. JRMS) (Academic Press, 1997).
53. Adams, P. D. et al. PHENIX: A comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213-221 (2010).
54. Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126-2132 (2004).
55. Tschopp, C. M. et al. Granzyme B, a novel mediator of allergic inflammation: its induction and release in blood basophils and human asthma. Blood 108, 2290-2299 (2006).