Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps

Jiun Bo Chen; Louisa K. James; Anna M. Davies; Yu Chang Bryan Wu; Joanne Rimmer; Valerie J. Lund; Jou Han Chen; James M. McDonnell; Yih Chih Chan; George H. Hutchins; Tse Wen Chang; Brian J. Sutton; Harsha H. Kariyawasam; Hannah J. Gould

doi:10.1016/j.jaci.2016.06.066

Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps

Jiun Bo Chen, Louisa K. James, Anna M. Davies, Yu Chang Bryan Wu, Joanne Rimmer, Valerie J. Lund, Jou Han Chen, James M. McDonnell, Yih Chih Chan, George H. Hutchins, Tse Wen Chang, Brian J. Sutton, Harsha H. Kariyawasam, Hannah J. Gould^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Chronic rhinosinusitis with nasal polyps is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against . Staphylococcus aureus enterotoxins (SAEs). Aspirin-exacerbated respiratory disease is a severe form of chronic rhinosinusitis with nasal polyps in which nearly all patients express anti-SAEs. Objectives: We aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity-determining regions (CDRs) or framework regions. Methods: Labeled staphylococcal enterotoxin (SE) A, SED, and SEE were used to isolate single SAE-specific B cells from the nasal polyps of 3 patients with aspirin-exacerbated respiratory disease by using fluorescence-activated cell sorting. Recombinant antibodies with "matched" heavy and light chains were cloned as IgG₁, and those of high affinity for specific SAEs, assayed by means of ELISA and surface plasmon resonance, were recloned as IgE and antigen-binding fragments. IgE activities were tested in basophil degranulation assays. Results: Thirty-seven SAE-specific, IgG- or IgA-expressing B cells were isolated and yielded 6 anti-SAE clones, 2 each for SEA, SED, and SEE. Competition binding assays revealed that the anti-SEE antibodies recognize nonoverlapping epitopes in SEE. Unexpectedly, each anti-SEE mediated SEE-induced basophil degranulation, and IgG₁ or antigen-binding fragments of each anti-SEE enhanced degranulation by the other anti-SEE. Conclusions: SEEs can activate basophils by simultaneously binding as antigens in the conventional manner to CDRs and as superantigens to framework regions of anti-SEE IgE in anti-SEE IgE-FcεRI complexes. Anti-SEE IgG₁s can enhance the activity of anti-SEE IgEs as conventional antibodies through CDRs or simultaneously as conventional antibodies and as "superantibodies" through CDRs and framework regions to SEEs in SEE-anti-SEE IgE-FcεRI complexes.

Original language	English
Journal	Journal of Allergy and Clinical Immunology
DOIs	https://doi.org/10.1016/j.jaci.2016.06.066
Publication status	Published - 19 Sept 2016

Keywords

Aspirin-exacerbated respiratory disease
Basophil
Chronic rhinosinusitis with nasal polyps
Staphylococcus aureus enterotoxin
Superantibody
Superantigen

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jaci.2016.06.066Licence: CC BY

Antibodies and Superantibodies in_CHEN_Accepted 13Jun2016_GREEN AAMAccepted author manuscript, 1.13 MB

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Chen, J. B., James, L. K., Davies, A. M., Wu, Y. C. B., Rimmer, J., Lund, V. J., Chen, J. H., McDonnell, J. M., Chan, Y. C., Hutchins, G. H., Chang, T. W., Sutton, B. J., Kariyawasam, H. H., & Gould, H. J. (2016). Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2016.06.066

@article{931578bc32b8482990574f223139290a,

title = "Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps",

abstract = "Background: Chronic rhinosinusitis with nasal polyps is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against . Staphylococcus aureus enterotoxins (SAEs). Aspirin-exacerbated respiratory disease is a severe form of chronic rhinosinusitis with nasal polyps in which nearly all patients express anti-SAEs. Objectives: We aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity-determining regions (CDRs) or framework regions. Methods: Labeled staphylococcal enterotoxin (SE) A, SED, and SEE were used to isolate single SAE-specific B cells from the nasal polyps of 3 patients with aspirin-exacerbated respiratory disease by using fluorescence-activated cell sorting. Recombinant antibodies with {"}matched{"} heavy and light chains were cloned as IgG1, and those of high affinity for specific SAEs, assayed by means of ELISA and surface plasmon resonance, were recloned as IgE and antigen-binding fragments. IgE activities were tested in basophil degranulation assays. Results: Thirty-seven SAE-specific, IgG- or IgA-expressing B cells were isolated and yielded 6 anti-SAE clones, 2 each for SEA, SED, and SEE. Competition binding assays revealed that the anti-SEE antibodies recognize nonoverlapping epitopes in SEE. Unexpectedly, each anti-SEE mediated SEE-induced basophil degranulation, and IgG1 or antigen-binding fragments of each anti-SEE enhanced degranulation by the other anti-SEE. Conclusions: SEEs can activate basophils by simultaneously binding as antigens in the conventional manner to CDRs and as superantigens to framework regions of anti-SEE IgE in anti-SEE IgE-FcεRI complexes. Anti-SEE IgG1s can enhance the activity of anti-SEE IgEs as conventional antibodies through CDRs or simultaneously as conventional antibodies and as {"}superantibodies{"} through CDRs and framework regions to SEEs in SEE-anti-SEE IgE-FcεRI complexes.",

keywords = "Aspirin-exacerbated respiratory disease, Basophil, Chronic rhinosinusitis with nasal polyps, Staphylococcus aureus enterotoxin, Superantibody, Superantigen",

author = "Chen, {Jiun Bo} and James, {Louisa K.} and Davies, {Anna M.} and Wu, {Yu Chang Bryan} and Joanne Rimmer and Lund, {Valerie J.} and Chen, {Jou Han} and McDonnell, {James M.} and Chan, {Yih Chih} and Hutchins, {George H.} and Chang, {Tse Wen} and Sutton, {Brian J.} and Kariyawasam, {Harsha H.} and Gould, {Hannah J.}",

year = "2016",

month = sep,

day = "19",

doi = "10.1016/j.jaci.2016.06.066",

language = "English",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "MOSBY, INC",

}

TY - JOUR

T1 - Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps

AU - Chen, Jiun Bo

AU - James, Louisa K.

AU - Davies, Anna M.

AU - Wu, Yu Chang Bryan

AU - Rimmer, Joanne

AU - Lund, Valerie J.

AU - Chen, Jou Han

AU - McDonnell, James M.

AU - Chan, Yih Chih

AU - Hutchins, George H.

AU - Chang, Tse Wen

AU - Sutton, Brian J.

AU - Kariyawasam, Harsha H.

AU - Gould, Hannah J.

PY - 2016/9/19

Y1 - 2016/9/19

N2 - Background: Chronic rhinosinusitis with nasal polyps is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against . Staphylococcus aureus enterotoxins (SAEs). Aspirin-exacerbated respiratory disease is a severe form of chronic rhinosinusitis with nasal polyps in which nearly all patients express anti-SAEs. Objectives: We aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity-determining regions (CDRs) or framework regions. Methods: Labeled staphylococcal enterotoxin (SE) A, SED, and SEE were used to isolate single SAE-specific B cells from the nasal polyps of 3 patients with aspirin-exacerbated respiratory disease by using fluorescence-activated cell sorting. Recombinant antibodies with "matched" heavy and light chains were cloned as IgG1, and those of high affinity for specific SAEs, assayed by means of ELISA and surface plasmon resonance, were recloned as IgE and antigen-binding fragments. IgE activities were tested in basophil degranulation assays. Results: Thirty-seven SAE-specific, IgG- or IgA-expressing B cells were isolated and yielded 6 anti-SAE clones, 2 each for SEA, SED, and SEE. Competition binding assays revealed that the anti-SEE antibodies recognize nonoverlapping epitopes in SEE. Unexpectedly, each anti-SEE mediated SEE-induced basophil degranulation, and IgG1 or antigen-binding fragments of each anti-SEE enhanced degranulation by the other anti-SEE. Conclusions: SEEs can activate basophils by simultaneously binding as antigens in the conventional manner to CDRs and as superantigens to framework regions of anti-SEE IgE in anti-SEE IgE-FcεRI complexes. Anti-SEE IgG1s can enhance the activity of anti-SEE IgEs as conventional antibodies through CDRs or simultaneously as conventional antibodies and as "superantibodies" through CDRs and framework regions to SEEs in SEE-anti-SEE IgE-FcεRI complexes.

AB - Background: Chronic rhinosinusitis with nasal polyps is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against . Staphylococcus aureus enterotoxins (SAEs). Aspirin-exacerbated respiratory disease is a severe form of chronic rhinosinusitis with nasal polyps in which nearly all patients express anti-SAEs. Objectives: We aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity-determining regions (CDRs) or framework regions. Methods: Labeled staphylococcal enterotoxin (SE) A, SED, and SEE were used to isolate single SAE-specific B cells from the nasal polyps of 3 patients with aspirin-exacerbated respiratory disease by using fluorescence-activated cell sorting. Recombinant antibodies with "matched" heavy and light chains were cloned as IgG1, and those of high affinity for specific SAEs, assayed by means of ELISA and surface plasmon resonance, were recloned as IgE and antigen-binding fragments. IgE activities were tested in basophil degranulation assays. Results: Thirty-seven SAE-specific, IgG- or IgA-expressing B cells were isolated and yielded 6 anti-SAE clones, 2 each for SEA, SED, and SEE. Competition binding assays revealed that the anti-SEE antibodies recognize nonoverlapping epitopes in SEE. Unexpectedly, each anti-SEE mediated SEE-induced basophil degranulation, and IgG1 or antigen-binding fragments of each anti-SEE enhanced degranulation by the other anti-SEE. Conclusions: SEEs can activate basophils by simultaneously binding as antigens in the conventional manner to CDRs and as superantigens to framework regions of anti-SEE IgE in anti-SEE IgE-FcεRI complexes. Anti-SEE IgG1s can enhance the activity of anti-SEE IgEs as conventional antibodies through CDRs or simultaneously as conventional antibodies and as "superantibodies" through CDRs and framework regions to SEEs in SEE-anti-SEE IgE-FcεRI complexes.

KW - Aspirin-exacerbated respiratory disease

KW - Basophil

KW - Chronic rhinosinusitis with nasal polyps

KW - Staphylococcus aureus enterotoxin

KW - Superantibody

KW - Superantigen

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U2 - 10.1016/j.jaci.2016.06.066

DO - 10.1016/j.jaci.2016.06.066

M3 - Article

SN - 0091-6749

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

ER -

Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps

Abstract

Keywords

UN SDGs

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