A role for anti-BP180 autoantibodies in chronic rhinosinusitis

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 hemidesmoso...

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Veröffentlicht in:The Laryngoscope 2013-09, Vol.123 (9), p.2104-2111
Hauptverfasser: Jeffe, Jill S., Seshadri, Sudarshan, Hamill, Kevin J., Huang, Julia He, Carter, Roderick, Suh, Lydia, Hulse, Kathryn E., Norton, James, Conley, David B., Chandra, Rakesh K., Kern, Robert C., Jones, Jonathan C. R., Schleimer, Robert P., Tan, Bruce K.
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container_end_page 2111
container_issue 9
container_start_page 2104
container_title The Laryngoscope
container_volume 123
creator Jeffe, Jill S.
Seshadri, Sudarshan
Hamill, Kevin J.
Huang, Julia He
Carter, Roderick
Suh, Lydia
Hulse, Kathryn E.
Norton, James
Conley, David B.
Chandra, Rakesh K.
Kern, Robert C.
Jones, Jonathan C. R.
Schleimer, Robert P.
Tan, Bruce K.
description 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
doi_str_mv 10.1002/lary.24016
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R. ; Schleimer, Robert P. ; Tan, Bruce K.</creator><creatorcontrib>Jeffe, Jill S. ; Seshadri, Sudarshan ; Hamill, Kevin J. ; Huang, Julia He ; Carter, Roderick ; Suh, Lydia ; Hulse, Kathryn E. ; Norton, James ; Conley, David B. ; Chandra, Rakesh K. ; Kern, Robert C. ; Jones, Jonathan C. R. ; Schleimer, Robert P. ; Tan, Bruce K.</creatorcontrib><description>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 &lt;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. Level of Evidence N/A. Laryngoscope, 123:2104–2111, 2013</description><identifier>ISSN: 0023-852X</identifier><identifier>EISSN: 1531-4995</identifier><identifier>DOI: 10.1002/lary.24016</identifier><identifier>PMID: 24167818</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; autoantibodies ; Autoantibodies - genetics ; Autoantibodies - metabolism ; Autoantigens - genetics ; Autoantigens - metabolism ; autoimmunity ; Blotting, Western ; bullous pemphigoid ; Case-Control Studies ; Cells, Cultured ; Chronic Disease ; Chronic rhinosinusitis ; Collagen Type XVII ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells - immunology ; Epithelial Cells - metabolism ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Medical research ; Middle Aged ; Nasal Mucosa - cytology ; Nasal Mucosa - immunology ; Nasal Mucosa - metabolism ; nasal polyps ; Non-Fibrillar Collagens - genetics ; Non-Fibrillar Collagens - metabolism ; Real-Time Polymerase Chain Reaction ; Reference Values ; Rhinitis - blood ; Rhinitis - immunology ; Rhinitis - physiopathology ; Sensitivity and Specificity ; sinusitis ; Sinusitis - blood ; Sinusitis - immunology ; Sinusitis - physiopathology ; Statistics, Nonparametric</subject><ispartof>The Laryngoscope, 2013-09, Vol.123 (9), p.2104-2111</ispartof><rights>Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5526-91c502821fb18e1e2f04e32d6969388980e8c5cb063184f5544af0f06dcc11c3</citedby><cites>FETCH-LOGICAL-c5526-91c502821fb18e1e2f04e32d6969388980e8c5cb063184f5544af0f06dcc11c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Flary.24016$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Flary.24016$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,315,781,785,886,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24167818$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jeffe, Jill S.</creatorcontrib><creatorcontrib>Seshadri, Sudarshan</creatorcontrib><creatorcontrib>Hamill, Kevin J.</creatorcontrib><creatorcontrib>Huang, Julia He</creatorcontrib><creatorcontrib>Carter, Roderick</creatorcontrib><creatorcontrib>Suh, Lydia</creatorcontrib><creatorcontrib>Hulse, Kathryn E.</creatorcontrib><creatorcontrib>Norton, James</creatorcontrib><creatorcontrib>Conley, David B.</creatorcontrib><creatorcontrib>Chandra, Rakesh K.</creatorcontrib><creatorcontrib>Kern, Robert C.</creatorcontrib><creatorcontrib>Jones, Jonathan C. R.</creatorcontrib><creatorcontrib>Schleimer, Robert P.</creatorcontrib><creatorcontrib>Tan, Bruce K.</creatorcontrib><title>A role for anti-BP180 autoantibodies in chronic rhinosinusitis</title><title>The Laryngoscope</title><addtitle>The Laryngoscope</addtitle><description>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 &lt;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. Level of Evidence N/A. Laryngoscope, 123:2104–2111, 2013</description><subject>Adult</subject><subject>Aged</subject><subject>autoantibodies</subject><subject>Autoantibodies - genetics</subject><subject>Autoantibodies - metabolism</subject><subject>Autoantigens - genetics</subject><subject>Autoantigens - metabolism</subject><subject>autoimmunity</subject><subject>Blotting, Western</subject><subject>bullous pemphigoid</subject><subject>Case-Control Studies</subject><subject>Cells, Cultured</subject><subject>Chronic Disease</subject><subject>Chronic rhinosinusitis</subject><subject>Collagen Type XVII</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epithelial Cells - immunology</subject><subject>Epithelial Cells - metabolism</subject><subject>Fluorescent Antibody Technique</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Medical research</subject><subject>Middle Aged</subject><subject>Nasal Mucosa - cytology</subject><subject>Nasal Mucosa - immunology</subject><subject>Nasal Mucosa - metabolism</subject><subject>nasal polyps</subject><subject>Non-Fibrillar Collagens - genetics</subject><subject>Non-Fibrillar Collagens - metabolism</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reference Values</subject><subject>Rhinitis - blood</subject><subject>Rhinitis - immunology</subject><subject>Rhinitis - physiopathology</subject><subject>Sensitivity and Specificity</subject><subject>sinusitis</subject><subject>Sinusitis - blood</subject><subject>Sinusitis - immunology</subject><subject>Sinusitis - physiopathology</subject><subject>Statistics, Nonparametric</subject><issn>0023-852X</issn><issn>1531-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kd9LHDEQx4O01FP70j9AFnwRYTWTX5u8CKdWKxxaiqD2JeRy2V50LzmT3bb-9-55elgf-jQM85kPM3wR-gJ4HzAmB41Jj_uEYRBraACcQsmU4h_QoB_SUnJys442cr7DGCrK8Se0ThiISoIcoMNhkWLjijqmwoTWl0ffQeLCdG1ctOM48S4XPhR2mmLwtkhTH2L2ocu-9XkLfaxNk93nl7qJrk6_Xh1_K0eXZ-fHw1FpOSeiVGA5JpJAPQbpwJEaM0fJRCihqJRKYictt2MsKEhWc86YqXGNxcRaAEs30eFSO-_GMzexLrTJNHqe_Kz_XUfj9b-T4Kf6V_ytqQRKFOsFuy-CFB86l1s989m6pjHBxS5rYKwCzIikPbrzDr2LXQr9dz1FKlCqeqb2lpRNMefk6tUxgPUiFb1IRT-n0sPbb89foa8x9AAsgT--cY__UenR8Mftq7Rc7vjcur-rHZPutahoxfX1xZkG_vOEXZMbLegTqwWlZQ</recordid><startdate>201309</startdate><enddate>201309</enddate><creator>Jeffe, Jill S.</creator><creator>Seshadri, Sudarshan</creator><creator>Hamill, Kevin J.</creator><creator>Huang, Julia He</creator><creator>Carter, Roderick</creator><creator>Suh, Lydia</creator><creator>Hulse, Kathryn E.</creator><creator>Norton, James</creator><creator>Conley, David B.</creator><creator>Chandra, Rakesh K.</creator><creator>Kern, Robert C.</creator><creator>Jones, Jonathan C. R.</creator><creator>Schleimer, Robert P.</creator><creator>Tan, Bruce K.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201309</creationdate><title>A role for anti-BP180 autoantibodies in chronic rhinosinusitis</title><author>Jeffe, Jill S. ; Seshadri, Sudarshan ; Hamill, Kevin J. ; Huang, Julia He ; Carter, Roderick ; Suh, Lydia ; Hulse, Kathryn E. ; Norton, James ; Conley, David B. ; Chandra, Rakesh K. ; Kern, Robert C. ; Jones, Jonathan C. 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R.</creatorcontrib><creatorcontrib>Schleimer, Robert P.</creatorcontrib><creatorcontrib>Tan, Bruce K.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Laryngoscope</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jeffe, Jill S.</au><au>Seshadri, Sudarshan</au><au>Hamill, Kevin J.</au><au>Huang, Julia He</au><au>Carter, Roderick</au><au>Suh, Lydia</au><au>Hulse, Kathryn E.</au><au>Norton, James</au><au>Conley, David B.</au><au>Chandra, Rakesh K.</au><au>Kern, Robert C.</au><au>Jones, Jonathan C. R.</au><au>Schleimer, Robert P.</au><au>Tan, Bruce K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A role for anti-BP180 autoantibodies in chronic rhinosinusitis</atitle><jtitle>The Laryngoscope</jtitle><addtitle>The Laryngoscope</addtitle><date>2013-09</date><risdate>2013</risdate><volume>123</volume><issue>9</issue><spage>2104</spage><epage>2111</epage><pages>2104-2111</pages><issn>0023-852X</issn><eissn>1531-4995</eissn><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 &lt;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. Level of Evidence N/A. Laryngoscope, 123:2104–2111, 2013</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>24167818</pmid><doi>10.1002/lary.24016</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Adult
Aged
autoantibodies
Autoantibodies - genetics
Autoantibodies - metabolism
Autoantigens - genetics
Autoantigens - metabolism
autoimmunity
Blotting, Western
bullous pemphigoid
Case-Control Studies
Cells, Cultured
Chronic Disease
Chronic rhinosinusitis
Collagen Type XVII
Enzyme-Linked Immunosorbent Assay
Epithelial Cells - immunology
Epithelial Cells - metabolism
Fluorescent Antibody Technique
Humans
Immunohistochemistry
Medical research
Middle Aged
Nasal Mucosa - cytology
Nasal Mucosa - immunology
Nasal Mucosa - metabolism
nasal polyps
Non-Fibrillar Collagens - genetics
Non-Fibrillar Collagens - metabolism
Real-Time Polymerase Chain Reaction
Reference Values
Rhinitis - blood
Rhinitis - immunology
Rhinitis - physiopathology
Sensitivity and Specificity
sinusitis
Sinusitis - blood
Sinusitis - immunology
Sinusitis - physiopathology
Statistics, Nonparametric
title A role for anti-BP180 autoantibodies in chronic rhinosinusitis
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