Sputum Antineutrophil Cytoplasmic Antibodies in Serum Antineutrophil Cytoplasmic Antibody-Negative Eosinophilic Granulomatosis with Polyangiitis
Eosinophilic granulomatosis with polyangiitis (eGPA) is a small-vessel vasculitis where 40% of patients present with serum antineutrophil cytoplasmic antibodies (ANCAs). We examined the presence and clinical relevance of sputum ANCAs in the serum ANCA patients with eGPA. ANCA was investigated in mat...
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| Veröffentlicht in: | American journal of respiratory and critical care medicine 2019-01, Vol.199 (2), p.158-170 |
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| creator | Mukherjee, Manali Thomas, Sruthi R Radford, Katherine Dvorkin-Gheva, Anna Davydchenko, Svetlana Kjarsgaard, Melanie Svenningsen, Sarah Almas, Sarah Felix, Lindsey C Stearns, Jennifer Li, Quan-Zhen Khalidi, Nader Lacy, Paige Nair, Parameswaran K |
| description | Eosinophilic granulomatosis with polyangiitis (eGPA) is a small-vessel vasculitis where 40% of patients present with serum antineutrophil cytoplasmic antibodies (ANCAs). We examined the presence and clinical relevance of sputum ANCAs in the serum ANCA
patients with eGPA.
ANCA was investigated in matched sputum and blood samples collected from 23 patients with eGPA (n = 10, serum ANCA
), 19 patients with eosinophilic asthma (prednisone dependent), and 13 healthy volunteers. IgG reactivity to common target antigens and cytokine profiles in sputum samples were examined. Pathogenicity of detected sputum ANCA was assessed using in vitro degranulation assays.
Most patients with eGPA (17 of 23, 74%) showed significantly increased sputum ANCAs compared with patients with eosinophilic asthma (P = 0.002) and healthy controls (P |
| doi_str_mv | 10.1164/rccm.201804-0809OC |
| format | Article |
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patients with eGPA.
ANCA was investigated in matched sputum and blood samples collected from 23 patients with eGPA (n = 10, serum ANCA
), 19 patients with eosinophilic asthma (prednisone dependent), and 13 healthy volunteers. IgG reactivity to common target antigens and cytokine profiles in sputum samples were examined. Pathogenicity of detected sputum ANCA was assessed using in vitro degranulation assays.
Most patients with eGPA (17 of 23, 74%) showed significantly increased sputum ANCAs compared with patients with eosinophilic asthma (P = 0.002) and healthy controls (P < 0.0001), irrespective of their serum ANCA status. In addition, 16 of 17 (94%) of sputum ANCA
patients had clinical manifestations of severe asthma compared with 3 of 6 (50%) in the sputum ANCA
subset (P = 0.04). Microarray analysis of 123 common antigens failed to reveal a specific target for the ANCA IgG. However, immunoprecipitated immunoglobulins from ANCA
sputum allowed extensive extracellular trap formations from both neutrophils and eosinophils in vitro, indicating pathogenicity of detected IgG autoantibodies. Cytokine analysis showed lung-localized increases in CXCL8 (neutrophil/eosinophil chemotaxis), CCL24 (eosinophil recruitment), and CXCL12 (lymphocyte recruitment) in the sputa from ANCA
patients (P < 0.01).
We report a novel finding of ANCA reactivity in the sputa of patients with eGPA in whom disease severity is driven by respiratory complications. Investigating localized autoimmunity may lead to the discovery of novel pathomechanisms, therapeutic targets, and optimal biomarkers for diagnosing and managing eGPA.</description><identifier>ISSN: 1073-449X</identifier><identifier>EISSN: 1535-4970</identifier><identifier>DOI: 10.1164/rccm.201804-0809OC</identifier><identifier>PMID: 30179583</identifier><language>eng</language><publisher>United States</publisher><ispartof>American journal of respiratory and critical care medicine, 2019-01, Vol.199 (2), p.158-170</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c303t-3481cd9456bccabe412ee52ee48cb756cc7d6547569ccc54ac558fae62ba50f03</citedby><cites>FETCH-LOGICAL-c303t-3481cd9456bccabe412ee52ee48cb756cc7d6547569ccc54ac558fae62ba50f03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4025,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30179583$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mukherjee, Manali</creatorcontrib><creatorcontrib>Thomas, Sruthi R</creatorcontrib><creatorcontrib>Radford, Katherine</creatorcontrib><creatorcontrib>Dvorkin-Gheva, Anna</creatorcontrib><creatorcontrib>Davydchenko, Svetlana</creatorcontrib><creatorcontrib>Kjarsgaard, Melanie</creatorcontrib><creatorcontrib>Svenningsen, Sarah</creatorcontrib><creatorcontrib>Almas, Sarah</creatorcontrib><creatorcontrib>Felix, Lindsey C</creatorcontrib><creatorcontrib>Stearns, Jennifer</creatorcontrib><creatorcontrib>Li, Quan-Zhen</creatorcontrib><creatorcontrib>Khalidi, Nader</creatorcontrib><creatorcontrib>Lacy, Paige</creatorcontrib><creatorcontrib>Nair, Parameswaran K</creatorcontrib><title>Sputum Antineutrophil Cytoplasmic Antibodies in Serum Antineutrophil Cytoplasmic Antibody-Negative Eosinophilic Granulomatosis with Polyangiitis</title><title>American journal of respiratory and critical care medicine</title><addtitle>Am J Respir Crit Care Med</addtitle><description>Eosinophilic granulomatosis with polyangiitis (eGPA) is a small-vessel vasculitis where 40% of patients present with serum antineutrophil cytoplasmic antibodies (ANCAs). We examined the presence and clinical relevance of sputum ANCAs in the serum ANCA
patients with eGPA.
ANCA was investigated in matched sputum and blood samples collected from 23 patients with eGPA (n = 10, serum ANCA
), 19 patients with eosinophilic asthma (prednisone dependent), and 13 healthy volunteers. IgG reactivity to common target antigens and cytokine profiles in sputum samples were examined. Pathogenicity of detected sputum ANCA was assessed using in vitro degranulation assays.
Most patients with eGPA (17 of 23, 74%) showed significantly increased sputum ANCAs compared with patients with eosinophilic asthma (P = 0.002) and healthy controls (P < 0.0001), irrespective of their serum ANCA status. In addition, 16 of 17 (94%) of sputum ANCA
patients had clinical manifestations of severe asthma compared with 3 of 6 (50%) in the sputum ANCA
subset (P = 0.04). Microarray analysis of 123 common antigens failed to reveal a specific target for the ANCA IgG. However, immunoprecipitated immunoglobulins from ANCA
sputum allowed extensive extracellular trap formations from both neutrophils and eosinophils in vitro, indicating pathogenicity of detected IgG autoantibodies. Cytokine analysis showed lung-localized increases in CXCL8 (neutrophil/eosinophil chemotaxis), CCL24 (eosinophil recruitment), and CXCL12 (lymphocyte recruitment) in the sputa from ANCA
patients (P < 0.01).
We report a novel finding of ANCA reactivity in the sputa of patients with eGPA in whom disease severity is driven by respiratory complications. Investigating localized autoimmunity may lead to the discovery of novel pathomechanisms, therapeutic targets, and optimal biomarkers for diagnosing and managing eGPA.</description><issn>1073-449X</issn><issn>1535-4970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqNUbtOwzAUtRCIlsIPMKCMLCl2bCf2WFWlIFUUqSCxRY7jtEZJHGwHlL_gk0mbwsxwdY_ueQz3AHCN4BShmNxZKatpBBGDJIQM8vX8BIwRxTQkPIGnPYYJDgnhbyNw4dw7hChiCJ6DEYYo4ZThMfjeNK1vq2BWe12r1lvT7HQZzDtvmlK4SssDlZlcKxfoOtgo-y95Fz6prfD6UwUL43R9EPb00oq6LU0lfH91wZf2u-DZlJ2ot1p77S7BWSFKp66OewJe7xcv84dwtV4-zmerUGKIfYgJQzLnhMaZlCJTBEVK0X4Ik1lCYymTPKakR1xKSYmQlLJCqDjKBIUFxBNwO-Q21ny0yvm00k6qshS1Mq1LI8g5YwlPSC-NBqm0xjmrirSxuhK2SxFM902k-ybSoYl0aKI33Rzz26xS-Z_l9_X4B24div0</recordid><startdate>20190115</startdate><enddate>20190115</enddate><creator>Mukherjee, Manali</creator><creator>Thomas, Sruthi R</creator><creator>Radford, Katherine</creator><creator>Dvorkin-Gheva, Anna</creator><creator>Davydchenko, Svetlana</creator><creator>Kjarsgaard, Melanie</creator><creator>Svenningsen, Sarah</creator><creator>Almas, Sarah</creator><creator>Felix, Lindsey C</creator><creator>Stearns, Jennifer</creator><creator>Li, Quan-Zhen</creator><creator>Khalidi, Nader</creator><creator>Lacy, Paige</creator><creator>Nair, Parameswaran K</creator><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20190115</creationdate><title>Sputum Antineutrophil Cytoplasmic Antibodies in Serum Antineutrophil Cytoplasmic Antibody-Negative Eosinophilic Granulomatosis with Polyangiitis</title><author>Mukherjee, Manali ; Thomas, Sruthi R ; Radford, Katherine ; Dvorkin-Gheva, Anna ; Davydchenko, Svetlana ; Kjarsgaard, Melanie ; Svenningsen, Sarah ; Almas, Sarah ; Felix, Lindsey C ; Stearns, Jennifer ; Li, Quan-Zhen ; Khalidi, Nader ; Lacy, Paige ; Nair, Parameswaran K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c303t-3481cd9456bccabe412ee52ee48cb756cc7d6547569ccc54ac558fae62ba50f03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mukherjee, Manali</creatorcontrib><creatorcontrib>Thomas, Sruthi R</creatorcontrib><creatorcontrib>Radford, Katherine</creatorcontrib><creatorcontrib>Dvorkin-Gheva, Anna</creatorcontrib><creatorcontrib>Davydchenko, Svetlana</creatorcontrib><creatorcontrib>Kjarsgaard, Melanie</creatorcontrib><creatorcontrib>Svenningsen, Sarah</creatorcontrib><creatorcontrib>Almas, Sarah</creatorcontrib><creatorcontrib>Felix, Lindsey C</creatorcontrib><creatorcontrib>Stearns, Jennifer</creatorcontrib><creatorcontrib>Li, Quan-Zhen</creatorcontrib><creatorcontrib>Khalidi, Nader</creatorcontrib><creatorcontrib>Lacy, Paige</creatorcontrib><creatorcontrib>Nair, Parameswaran K</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of respiratory and critical care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mukherjee, Manali</au><au>Thomas, Sruthi R</au><au>Radford, Katherine</au><au>Dvorkin-Gheva, Anna</au><au>Davydchenko, Svetlana</au><au>Kjarsgaard, Melanie</au><au>Svenningsen, Sarah</au><au>Almas, Sarah</au><au>Felix, Lindsey C</au><au>Stearns, Jennifer</au><au>Li, Quan-Zhen</au><au>Khalidi, Nader</au><au>Lacy, Paige</au><au>Nair, Parameswaran K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sputum Antineutrophil Cytoplasmic Antibodies in Serum Antineutrophil Cytoplasmic Antibody-Negative Eosinophilic Granulomatosis with Polyangiitis</atitle><jtitle>American journal of respiratory and critical care medicine</jtitle><addtitle>Am J Respir Crit Care Med</addtitle><date>2019-01-15</date><risdate>2019</risdate><volume>199</volume><issue>2</issue><spage>158</spage><epage>170</epage><pages>158-170</pages><issn>1073-449X</issn><eissn>1535-4970</eissn><abstract>Eosinophilic granulomatosis with polyangiitis (eGPA) is a small-vessel vasculitis where 40% of patients present with serum antineutrophil cytoplasmic antibodies (ANCAs). We examined the presence and clinical relevance of sputum ANCAs in the serum ANCA
patients with eGPA.
ANCA was investigated in matched sputum and blood samples collected from 23 patients with eGPA (n = 10, serum ANCA
), 19 patients with eosinophilic asthma (prednisone dependent), and 13 healthy volunteers. IgG reactivity to common target antigens and cytokine profiles in sputum samples were examined. Pathogenicity of detected sputum ANCA was assessed using in vitro degranulation assays.
Most patients with eGPA (17 of 23, 74%) showed significantly increased sputum ANCAs compared with patients with eosinophilic asthma (P = 0.002) and healthy controls (P < 0.0001), irrespective of their serum ANCA status. In addition, 16 of 17 (94%) of sputum ANCA
patients had clinical manifestations of severe asthma compared with 3 of 6 (50%) in the sputum ANCA
subset (P = 0.04). Microarray analysis of 123 common antigens failed to reveal a specific target for the ANCA IgG. However, immunoprecipitated immunoglobulins from ANCA
sputum allowed extensive extracellular trap formations from both neutrophils and eosinophils in vitro, indicating pathogenicity of detected IgG autoantibodies. Cytokine analysis showed lung-localized increases in CXCL8 (neutrophil/eosinophil chemotaxis), CCL24 (eosinophil recruitment), and CXCL12 (lymphocyte recruitment) in the sputa from ANCA
patients (P < 0.01).
We report a novel finding of ANCA reactivity in the sputa of patients with eGPA in whom disease severity is driven by respiratory complications. Investigating localized autoimmunity may lead to the discovery of novel pathomechanisms, therapeutic targets, and optimal biomarkers for diagnosing and managing eGPA.</abstract><cop>United States</cop><pmid>30179583</pmid><doi>10.1164/rccm.201804-0809OC</doi><tpages>13</tpages></addata></record> |
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| title | Sputum Antineutrophil Cytoplasmic Antibodies in Serum Antineutrophil Cytoplasmic Antibody-Negative Eosinophilic Granulomatosis with Polyangiitis |
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