A role for anti-BP180 autoantibodies in chronic rhinosinusitis

Jill S. Jeffe, Sudarshan Seshadri, Kevin J. Hamill, Julia He Huang, Roderick Carter, Lydia Suh, Kathryn E Hulse, James Norton, David B Conley Jr, Rakesh K. Chandra, Robert C Kern, Jonathan C.R. Jones, Robert P Schleimer, Bruce Kuang-Huay Tan*

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objectives/Hypothesis Chronic Rhinosinusitis (CRS) is accompanied by evidence of a vigorous adaptive immune response, and emerging studies demonstrate that some nasal polyps manifest a polyclonal autoantibody response. We previously found that antibodies against BP180, a component of the hemidesmosome complex and the dominant epitope in autoimmune bullous pemphigoid, were found at elevated levels in nasal polyp tissue. Given the critical role of hemidesmosomes in maintaining epithelial integrity, we sought to investigate the distribution of BP180 in nasal tissue and evaluate for evidence of systemic autoimmunity against this antigen in CRS. Study Design Case-control experimental study. Methods The expression and distribution of BP180 in cultured nasal epithelial cells and normal nasal tissue were confirmed using real-time polymerase chain reaction (PCR), Western immunoblotting, immunofluorescence and immunohistochemistry. Sera were collected from three groups: control, CRSsNP, and CRSwNP. A commercially available ELISA was utilized to compare anti-BP180 autoantibody levels in sera. Results BP180 is expressed in nasal epithelium, but is not confined to the basement membrane as it is in human skin. In cultured nasal epithelial cells, confocal immunofluorescence showed a punctate distribution of BP180 along the basal surface, consistent with its distribution in epithelial keratinocytes. There are significantly higher levels of circulating nonpathologic anti-BP180 autoantibodies in CRS patients compared with normal controls (P <0.05). Conclusions BP180 is more widely expressed in nasal epithelium versus skin, although it appears to play a similar role in the formation of hemidesmosomes along the basement membrane. Further investigations are ongoing to characterize the pathogenicity of the anti-epithelial antibody response in CRS.

Original languageEnglish (US)
Pages (from-to)2104-2111
Number of pages8
JournalLaryngoscope
Volume123
Issue number9
DOIs
StatePublished - Sep 1 2013

Fingerprint

Hemidesmosomes
Nose
Autoantibodies
Nasal Polyps
Nasal Mucosa
Basement Membrane
Fluorescent Antibody Technique
Epithelial Cells
Bullous Pemphigoid
Skin
Adaptive Immunity
Serum
Autoimmunity
Keratinocytes
Antibody Formation
Virulence
Case-Control Studies
Real-Time Polymerase Chain Reaction
Epitopes
Anti-Idiotypic Antibodies

Keywords

  • Chronic rhinosinusitis
  • autoantibodies
  • autoimmunity
  • bullous pemphigoid
  • nasal polyps
  • sinusitis

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Jeffe, J. S., Seshadri, S., Hamill, K. J., Huang, J. H., Carter, R., Suh, L., ... Tan, B. K-H. (2013). A role for anti-BP180 autoantibodies in chronic rhinosinusitis. Laryngoscope, 123(9), 2104-2111. https://doi.org/10.1002/lary.24016
Jeffe, Jill S. ; Seshadri, Sudarshan ; Hamill, Kevin J. ; Huang, Julia He ; Carter, Roderick ; Suh, Lydia ; Hulse, Kathryn E ; Norton, James ; Conley Jr, David B ; Chandra, Rakesh K. ; Kern, Robert C ; Jones, Jonathan C.R. ; Schleimer, Robert P ; Tan, Bruce Kuang-Huay. / A role for anti-BP180 autoantibodies in chronic rhinosinusitis. In: Laryngoscope. 2013 ; Vol. 123, No. 9. pp. 2104-2111.
@article{0892336b5d8345e28852d9a3cb7b1539,
title = "A role for anti-BP180 autoantibodies in chronic rhinosinusitis",
abstract = "Objectives/Hypothesis Chronic Rhinosinusitis (CRS) is accompanied by evidence of a vigorous adaptive immune response, and emerging studies demonstrate that some nasal polyps manifest a polyclonal autoantibody response. We previously found that antibodies against BP180, a component of the hemidesmosome complex and the dominant epitope in autoimmune bullous pemphigoid, were found at elevated levels in nasal polyp tissue. Given the critical role of hemidesmosomes in maintaining epithelial integrity, we sought to investigate the distribution of BP180 in nasal tissue and evaluate for evidence of systemic autoimmunity against this antigen in CRS. Study Design Case-control experimental study. Methods The expression and distribution of BP180 in cultured nasal epithelial cells and normal nasal tissue were confirmed using real-time polymerase chain reaction (PCR), Western immunoblotting, immunofluorescence and immunohistochemistry. Sera were collected from three groups: control, CRSsNP, and CRSwNP. A commercially available ELISA was utilized to compare anti-BP180 autoantibody levels in sera. Results BP180 is expressed in nasal epithelium, but is not confined to the basement membrane as it is in human skin. In cultured nasal epithelial cells, confocal immunofluorescence showed a punctate distribution of BP180 along the basal surface, consistent with its distribution in epithelial keratinocytes. There are significantly higher levels of circulating nonpathologic anti-BP180 autoantibodies in CRS patients compared with normal controls (P <0.05). Conclusions BP180 is more widely expressed in nasal epithelium versus skin, although it appears to play a similar role in the formation of hemidesmosomes along the basement membrane. Further investigations are ongoing to characterize the pathogenicity of the anti-epithelial antibody response in CRS.",
keywords = "Chronic rhinosinusitis, autoantibodies, autoimmunity, bullous pemphigoid, nasal polyps, sinusitis",
author = "Jeffe, {Jill S.} and Sudarshan Seshadri and Hamill, {Kevin J.} and Huang, {Julia He} and Roderick Carter and Lydia Suh and Hulse, {Kathryn E} and James Norton and {Conley Jr}, {David B} and Chandra, {Rakesh K.} and Kern, {Robert C} and Jones, {Jonathan C.R.} and Schleimer, {Robert P} and Tan, {Bruce Kuang-Huay}",
year = "2013",
month = "9",
day = "1",
doi = "10.1002/lary.24016",
language = "English (US)",
volume = "123",
pages = "2104--2111",
journal = "Laryngoscope",
issn = "0023-852X",
publisher = "John Wiley and Sons Inc.",
number = "9",

}

Jeffe, JS, Seshadri, S, Hamill, KJ, Huang, JH, Carter, R, Suh, L, Hulse, KE, Norton, J, Conley Jr, DB, Chandra, RK, Kern, RC, Jones, JCR, Schleimer, RP & Tan, BK-H 2013, 'A role for anti-BP180 autoantibodies in chronic rhinosinusitis', Laryngoscope, vol. 123, no. 9, pp. 2104-2111. https://doi.org/10.1002/lary.24016

A role for anti-BP180 autoantibodies in chronic rhinosinusitis. / Jeffe, Jill S.; Seshadri, Sudarshan; Hamill, Kevin J.; Huang, Julia He; Carter, Roderick; Suh, Lydia; Hulse, Kathryn E; Norton, James; Conley Jr, David B; Chandra, Rakesh K.; Kern, Robert C; Jones, Jonathan C.R.; Schleimer, Robert P; Tan, Bruce Kuang-Huay.

In: Laryngoscope, Vol. 123, No. 9, 01.09.2013, p. 2104-2111.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A role for anti-BP180 autoantibodies in chronic rhinosinusitis

AU - Jeffe, Jill S.

AU - Seshadri, Sudarshan

AU - Hamill, Kevin J.

AU - Huang, Julia He

AU - Carter, Roderick

AU - Suh, Lydia

AU - Hulse, Kathryn E

AU - Norton, James

AU - Conley Jr, David B

AU - Chandra, Rakesh K.

AU - Kern, Robert C

AU - Jones, Jonathan C.R.

AU - Schleimer, Robert P

AU - Tan, Bruce Kuang-Huay

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Objectives/Hypothesis Chronic Rhinosinusitis (CRS) is accompanied by evidence of a vigorous adaptive immune response, and emerging studies demonstrate that some nasal polyps manifest a polyclonal autoantibody response. We previously found that antibodies against BP180, a component of the hemidesmosome complex and the dominant epitope in autoimmune bullous pemphigoid, were found at elevated levels in nasal polyp tissue. Given the critical role of hemidesmosomes in maintaining epithelial integrity, we sought to investigate the distribution of BP180 in nasal tissue and evaluate for evidence of systemic autoimmunity against this antigen in CRS. Study Design Case-control experimental study. Methods The expression and distribution of BP180 in cultured nasal epithelial cells and normal nasal tissue were confirmed using real-time polymerase chain reaction (PCR), Western immunoblotting, immunofluorescence and immunohistochemistry. Sera were collected from three groups: control, CRSsNP, and CRSwNP. A commercially available ELISA was utilized to compare anti-BP180 autoantibody levels in sera. Results BP180 is expressed in nasal epithelium, but is not confined to the basement membrane as it is in human skin. In cultured nasal epithelial cells, confocal immunofluorescence showed a punctate distribution of BP180 along the basal surface, consistent with its distribution in epithelial keratinocytes. There are significantly higher levels of circulating nonpathologic anti-BP180 autoantibodies in CRS patients compared with normal controls (P <0.05). Conclusions BP180 is more widely expressed in nasal epithelium versus skin, although it appears to play a similar role in the formation of hemidesmosomes along the basement membrane. Further investigations are ongoing to characterize the pathogenicity of the anti-epithelial antibody response in CRS.

AB - Objectives/Hypothesis Chronic Rhinosinusitis (CRS) is accompanied by evidence of a vigorous adaptive immune response, and emerging studies demonstrate that some nasal polyps manifest a polyclonal autoantibody response. We previously found that antibodies against BP180, a component of the hemidesmosome complex and the dominant epitope in autoimmune bullous pemphigoid, were found at elevated levels in nasal polyp tissue. Given the critical role of hemidesmosomes in maintaining epithelial integrity, we sought to investigate the distribution of BP180 in nasal tissue and evaluate for evidence of systemic autoimmunity against this antigen in CRS. Study Design Case-control experimental study. Methods The expression and distribution of BP180 in cultured nasal epithelial cells and normal nasal tissue were confirmed using real-time polymerase chain reaction (PCR), Western immunoblotting, immunofluorescence and immunohistochemistry. Sera were collected from three groups: control, CRSsNP, and CRSwNP. A commercially available ELISA was utilized to compare anti-BP180 autoantibody levels in sera. Results BP180 is expressed in nasal epithelium, but is not confined to the basement membrane as it is in human skin. In cultured nasal epithelial cells, confocal immunofluorescence showed a punctate distribution of BP180 along the basal surface, consistent with its distribution in epithelial keratinocytes. There are significantly higher levels of circulating nonpathologic anti-BP180 autoantibodies in CRS patients compared with normal controls (P <0.05). Conclusions BP180 is more widely expressed in nasal epithelium versus skin, although it appears to play a similar role in the formation of hemidesmosomes along the basement membrane. Further investigations are ongoing to characterize the pathogenicity of the anti-epithelial antibody response in CRS.

KW - Chronic rhinosinusitis

KW - autoantibodies

KW - autoimmunity

KW - bullous pemphigoid

KW - nasal polyps

KW - sinusitis

UR - http://www.scopus.com/inward/record.url?scp=84883196656&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883196656&partnerID=8YFLogxK

U2 - 10.1002/lary.24016

DO - 10.1002/lary.24016

M3 - Article

VL - 123

SP - 2104

EP - 2111

JO - Laryngoscope

JF - Laryngoscope

SN - 0023-852X

IS - 9

ER -

Jeffe JS, Seshadri S, Hamill KJ, Huang JH, Carter R, Suh L et al. A role for anti-BP180 autoantibodies in chronic rhinosinusitis. Laryngoscope. 2013 Sep 1;123(9):2104-2111. https://doi.org/10.1002/lary.24016