Neutrophil extracellular traps as a potential source of autoantigen in cocaine-associated autoimmunity
Exposure to illicit cocaine and its frequent adulterant, levamisole, is associated with ANCAs targeting neutrophil elastase (NE), neutropenia and vasculitic/thrombotic skin purpura. The mechanisms of cocaine/levamisole-associated autoimmunity (CLAA) are unknown. The aim of this study was to assess t...
Gespeichert in:
| Veröffentlicht in: | Rheumatology (Oxford, England) Jg. 56; H. 4; S. 638 |
|---|---|
| Hauptverfasser: | , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
England
01.04.2017
|
| Schlagworte: | |
| ISSN: | 1462-0332, 1462-0332 |
| Online-Zugang: | Weitere Angaben |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| Abstract | Exposure to illicit cocaine and its frequent adulterant, levamisole, is associated with ANCAs targeting neutrophil elastase (NE), neutropenia and vasculitic/thrombotic skin purpura. The mechanisms of cocaine/levamisole-associated autoimmunity (CLAA) are unknown. The aim of this study was to assess the ability of cocaine and levamisole to induce the release of neutrophil extracellular traps (NETs), a potential source of autoantigen and tissue injury.
We performed quantitative and qualitative assessment of NET formation in neutrophils from healthy donors exposed to either drug in vitro . In addition, IgG from sera of individuals with CLAA (CLAA-IgG) was assessed for its ability to enhance formation of, and to bind to, drug-induced NETs.
Both cocaine and levamisole could induce formation of NETs enriched in NE and, potentially, inflammatory mitochondrial DNA. Both drugs could also augment simultaneous release of B cell-activating factor belonging to the TNF family (BAFF). CLAA-IgG, but not IgG from healthy individuals, could potentiate drug-induced NETosis. Furthermore, CLAA-IgG, but not ANCA + control IgG, bound to drug-induced NETs in a pattern consistent with NE targeting.
Both cocaine and levamisole may contribute to the development of ANCAs by inducing release of potentially inflammatory NETs in association with NE autoantigen and BAFF. Enhancement of drug-induced NET release by CLAA-IgG provides a potential mechanism linking vasculitis/pupuric skin disease to acute drug exposure in patients with CLAA. Further study of this under-recognized form of autoimmunity will be likely to provide mechanistic insight into ANCA-associated vasculitis and other diseases associated with NETosis. |
|---|---|
| AbstractList | Exposure to illicit cocaine and its frequent adulterant, levamisole, is associated with ANCAs targeting neutrophil elastase (NE), neutropenia and vasculitic/thrombotic skin purpura. The mechanisms of cocaine/levamisole-associated autoimmunity (CLAA) are unknown. The aim of this study was to assess the ability of cocaine and levamisole to induce the release of neutrophil extracellular traps (NETs), a potential source of autoantigen and tissue injury.ObjectiveExposure to illicit cocaine and its frequent adulterant, levamisole, is associated with ANCAs targeting neutrophil elastase (NE), neutropenia and vasculitic/thrombotic skin purpura. The mechanisms of cocaine/levamisole-associated autoimmunity (CLAA) are unknown. The aim of this study was to assess the ability of cocaine and levamisole to induce the release of neutrophil extracellular traps (NETs), a potential source of autoantigen and tissue injury.We performed quantitative and qualitative assessment of NET formation in neutrophils from healthy donors exposed to either drug in vitro . In addition, IgG from sera of individuals with CLAA (CLAA-IgG) was assessed for its ability to enhance formation of, and to bind to, drug-induced NETs.MethodsWe performed quantitative and qualitative assessment of NET formation in neutrophils from healthy donors exposed to either drug in vitro . In addition, IgG from sera of individuals with CLAA (CLAA-IgG) was assessed for its ability to enhance formation of, and to bind to, drug-induced NETs.Both cocaine and levamisole could induce formation of NETs enriched in NE and, potentially, inflammatory mitochondrial DNA. Both drugs could also augment simultaneous release of B cell-activating factor belonging to the TNF family (BAFF). CLAA-IgG, but not IgG from healthy individuals, could potentiate drug-induced NETosis. Furthermore, CLAA-IgG, but not ANCA + control IgG, bound to drug-induced NETs in a pattern consistent with NE targeting.ResultsBoth cocaine and levamisole could induce formation of NETs enriched in NE and, potentially, inflammatory mitochondrial DNA. Both drugs could also augment simultaneous release of B cell-activating factor belonging to the TNF family (BAFF). CLAA-IgG, but not IgG from healthy individuals, could potentiate drug-induced NETosis. Furthermore, CLAA-IgG, but not ANCA + control IgG, bound to drug-induced NETs in a pattern consistent with NE targeting.Both cocaine and levamisole may contribute to the development of ANCAs by inducing release of potentially inflammatory NETs in association with NE autoantigen and BAFF. Enhancement of drug-induced NET release by CLAA-IgG provides a potential mechanism linking vasculitis/pupuric skin disease to acute drug exposure in patients with CLAA. Further study of this under-recognized form of autoimmunity will be likely to provide mechanistic insight into ANCA-associated vasculitis and other diseases associated with NETosis.ConclusionBoth cocaine and levamisole may contribute to the development of ANCAs by inducing release of potentially inflammatory NETs in association with NE autoantigen and BAFF. Enhancement of drug-induced NET release by CLAA-IgG provides a potential mechanism linking vasculitis/pupuric skin disease to acute drug exposure in patients with CLAA. Further study of this under-recognized form of autoimmunity will be likely to provide mechanistic insight into ANCA-associated vasculitis and other diseases associated with NETosis. Exposure to illicit cocaine and its frequent adulterant, levamisole, is associated with ANCAs targeting neutrophil elastase (NE), neutropenia and vasculitic/thrombotic skin purpura. The mechanisms of cocaine/levamisole-associated autoimmunity (CLAA) are unknown. The aim of this study was to assess the ability of cocaine and levamisole to induce the release of neutrophil extracellular traps (NETs), a potential source of autoantigen and tissue injury. We performed quantitative and qualitative assessment of NET formation in neutrophils from healthy donors exposed to either drug in vitro . In addition, IgG from sera of individuals with CLAA (CLAA-IgG) was assessed for its ability to enhance formation of, and to bind to, drug-induced NETs. Both cocaine and levamisole could induce formation of NETs enriched in NE and, potentially, inflammatory mitochondrial DNA. Both drugs could also augment simultaneous release of B cell-activating factor belonging to the TNF family (BAFF). CLAA-IgG, but not IgG from healthy individuals, could potentiate drug-induced NETosis. Furthermore, CLAA-IgG, but not ANCA + control IgG, bound to drug-induced NETs in a pattern consistent with NE targeting. Both cocaine and levamisole may contribute to the development of ANCAs by inducing release of potentially inflammatory NETs in association with NE autoantigen and BAFF. Enhancement of drug-induced NET release by CLAA-IgG provides a potential mechanism linking vasculitis/pupuric skin disease to acute drug exposure in patients with CLAA. Further study of this under-recognized form of autoimmunity will be likely to provide mechanistic insight into ANCA-associated vasculitis and other diseases associated with NETosis. |
| Author | Lood, Christian Hughes, Grant C |
| Author_xml | – sequence: 1 givenname: Christian surname: Lood fullname: Lood, Christian organization: Department of Medicine, Division of Rheumatology, University of Washington, Seattle, WA, USA – sequence: 2 givenname: Grant C surname: Hughes fullname: Hughes, Grant C organization: Department of Medicine, Division of Rheumatology, University of Washington, Seattle, WA, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27354687$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkFtLxDAQhYOsuBf9BYLk0Ze6uTRN-yiLN1j0RZ9LNp3uRtuk5oLuv7fqCsLAHA7fHDgzRxPrLCB0TskVJRVf-h2kXkXXue1--QYfTBRHaEbzgmWEczb5p6doHsIrIURQXp6gKZNc5EUpZ6h9hBS9G3amw_AZvdLQdalTHo96CFiNgwcXwUajOhxc8hqwa7FK0anR3ILFxmLttDIWMhWC00ZFaH4I0_fJmrg_Rcet6gKcHfYCvdzePK_us_XT3cPqep1pzkXMKFSiACEIASXavCJUbyRrGIGKljltmlw2rKk2SlANZCMlIzQnpWwLriSXOVugy9_cwbv3BCHWvQnflZQFl0JNS1bI8UDIEb04oGnTQ1MP3vTK7-u_37AvWtxtAg |
| CitedBy_id | crossref_primary_10_1007_s10067_021_05790_9 crossref_primary_10_3389_fimmu_2022_974826 crossref_primary_10_1007_s00393_022_01217_1 crossref_primary_10_1161_ATVBAHA_116_308206 crossref_primary_10_3389_fimmu_2020_619705 crossref_primary_10_3389_fimmu_2019_01028 crossref_primary_10_1159_000500544 crossref_primary_10_1080_09273948_2021_1906913 crossref_primary_10_1007_s11926_017_0653_9 crossref_primary_10_1007_s12016_020_08816_3 crossref_primary_10_1016_j_jbspin_2017_05_022 crossref_primary_10_1111_adb_13166 crossref_primary_10_1111_ijd_17447 crossref_primary_10_4049_jimmunol_1601855 crossref_primary_10_1007_s40674_024_00215_5 crossref_primary_10_7759_cureus_83425 crossref_primary_10_1093_rheumatology_kew381 crossref_primary_10_1016_j_reumae_2017_11_007 crossref_primary_10_1155_2024_7388799 crossref_primary_10_3389_fimmu_2020_01622 crossref_primary_10_1007_s00296_019_04410_9 crossref_primary_10_1007_s11926_022_01088_0 crossref_primary_10_1007_s00296_019_04426_1 crossref_primary_10_1016_j_monrhu_2017_04_005 crossref_primary_10_1016_j_reuma_2017_11_002 crossref_primary_10_1080_1744666X_2023_2270774 |
| ContentType | Journal Article |
| Copyright | The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com |
| Copyright_xml | – notice: The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1093/rheumatology/kew256 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1462-0332 |
| ExternalDocumentID | 27354687 |
| Genre | Journal Article |
| GroupedDBID | --- -E4 .2P .I3 .XZ .ZR 08P 0R~ 18M 1TH 29P 2WC 354 4.4 48X 53G 5RE 5VS 5WA 5WD 70D AABZA AACZT AAJKP AAJQQ AAMDB AAMVS AAOGV AAPNW AAPQZ AAPXW AARHZ AAUAY AAUQX AAVAP AAWTL ABDFA ABEJV ABEUO ABGNP ABIXL ABJNI ABKDP ABLJU ABNHQ ABNKS ABOCM ABPTD ABQLI ABQNK ABVGC ABXVV ABZBJ ACGFO ACGFS ACPRK ACUFI ACUTJ ACUTO ACYHN ADBBV ADEYI ADEZT ADGZP ADHKW ADHZD ADIPN ADNBA ADOCK ADQBN ADRTK ADVEK ADYVW ADZXQ AEGPL AEGXH AEJOX AEKSI AEMDU AEMQT AENEX AENZO AEPUE AETBJ AEWNT AFFZL AFIYH AFOFC AFXAL AGINJ AGKEF AGORE AGSYK AGUTN AHMBA AHMMS AHXPO AIAGR AIJHB AJBYB AJEEA AJNCP AKWXX ALMA_UNASSIGNED_HOLDINGS ALUQC ALXQX APIBT APWMN ATGXG AXUDD BAWUL BAYMD BCRHZ BEYMZ BHONS BTRTY BVRKM C45 CDBKE CGR CS3 CUY CVF CZ4 DAKXR DIK DILTD DU5 D~K E3Z EBD EBS ECM EE~ EIF EJD EMOBN ENERS F5P F9B FECEO FLUFQ FOEOM FOTVD FQBLK GAUVT GJXCC GX1 H13 H5~ HAR HW0 HZ~ IOX J21 JXSIZ KAQDR KBUDW KOP KQ8 KSI KSN L7B M-Z MHKGH N9A NGC NOMLY NOYVH NPM NU- NVLIB O9- OAUYM OAWHX OBH OCZFY ODMLO OHH OJQWA OJZSN OPAEJ OVD OWPYF P2P PAFKI PEELM PQQKQ Q1. Q5Y R44 RD5 ROL ROX RUSNO RW1 RXO SV3 TCURE TEORI TJX TR2 VVN W8F WOQ X7H YAYTL YKOAZ YXANX ZKX ZY1 ~91 7X8 |
| ID | FETCH-LOGICAL-c335t-1e956e5500ea5f4901cb72d20e91841dd47d2d9ba51ce0b772014087f63a73742 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 76 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000398497700022&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1462-0332 |
| IngestDate | Sun Sep 28 06:57:39 EDT 2025 Mon Jul 21 06:05:20 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 4 |
| Keywords | drug-induced rheumatic disease vasculitis autoantibodies neutrophils autoantigens anti-neutrophil cytoplasm antibody |
| Language | English |
| License | The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c335t-1e956e5500ea5f4901cb72d20e91841dd47d2d9ba51ce0b772014087f63a73742 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | https://academic.oup.com/rheumatology/article-pdf/56/4/638/24245634/kew256.pdf |
| PMID | 27354687 |
| PQID | 1826708757 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_1826708757 pubmed_primary_27354687 |
| PublicationCentury | 2000 |
| PublicationDate | 2017-04-01 |
| PublicationDateYYYYMMDD | 2017-04-01 |
| PublicationDate_xml | – month: 04 year: 2017 text: 2017-04-01 day: 01 |
| PublicationDecade | 2010 |
| PublicationPlace | England |
| PublicationPlace_xml | – name: England |
| PublicationTitle | Rheumatology (Oxford, England) |
| PublicationTitleAlternate | Rheumatology (Oxford) |
| PublicationYear | 2017 |
| References | 19737141 - Clin Exp Immunol. 2009 Nov;158(2):155-63 19609275 - Cell Death Differ. 2009 Nov;16(11):1438-44 26432901 - J Leukoc Biol. 2016 Feb;99(2):253-64 22777766 - Arthritis Rheum. 2012 Nov;64(11):3779-87 24366358 - Blood. 2014 May 1;123(18):2768-76 24073241 - PLoS One. 2013 Sep 20;8(9):e75141 24276086 - Curr Opin Rheumatol. 2014 Jan;26(1):42-9 22345666 - J Immunol. 2012 Apr 1;188(7):3522-31 23196324 - Curr Opin Rheumatol. 2013 Jan;25(1):50-5 15001782 - Science. 2004 Mar 5;303(5663):1532-5 6341264 - Int J Immunopharmacol. 1983;5(1):1-9 8870370 - Ear Nose Throat J. 1996 Sep;75(9):623-6 25003769 - Nat Rev Rheumatol. 2014 Aug;10(8):463-73 9456523 - J Forensic Sci. 1998 Jan;43(1):41-5 20019655 - MMWR Morb Mortal Wkly Rep. 2009 Dec 18;58(49):1381-5 15457464 - Arthritis Rheum. 2004 Sep;50(9):2954-65 26779811 - Nat Med. 2016 Feb;22(2):146-53 |
| References_xml | – reference: 26779811 - Nat Med. 2016 Feb;22(2):146-53 – reference: 26432901 - J Leukoc Biol. 2016 Feb;99(2):253-64 – reference: 9456523 - J Forensic Sci. 1998 Jan;43(1):41-5 – reference: 20019655 - MMWR Morb Mortal Wkly Rep. 2009 Dec 18;58(49):1381-5 – reference: 22777766 - Arthritis Rheum. 2012 Nov;64(11):3779-87 – reference: 24366358 - Blood. 2014 May 1;123(18):2768-76 – reference: 24073241 - PLoS One. 2013 Sep 20;8(9):e75141 – reference: 22345666 - J Immunol. 2012 Apr 1;188(7):3522-31 – reference: 19609275 - Cell Death Differ. 2009 Nov;16(11):1438-44 – reference: 8870370 - Ear Nose Throat J. 1996 Sep;75(9):623-6 – reference: 25003769 - Nat Rev Rheumatol. 2014 Aug;10(8):463-73 – reference: 19737141 - Clin Exp Immunol. 2009 Nov;158(2):155-63 – reference: 15457464 - Arthritis Rheum. 2004 Sep;50(9):2954-65 – reference: 15001782 - Science. 2004 Mar 5;303(5663):1532-5 – reference: 24276086 - Curr Opin Rheumatol. 2014 Jan;26(1):42-9 – reference: 23196324 - Curr Opin Rheumatol. 2013 Jan;25(1):50-5 – reference: 6341264 - Int J Immunopharmacol. 1983;5(1):1-9 |
| SSID | ssj0005138 |
| Score | 2.481217 |
| Snippet | Exposure to illicit cocaine and its frequent adulterant, levamisole, is associated with ANCAs targeting neutrophil elastase (NE), neutropenia and... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 638 |
| SubjectTerms | Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - chemically induced Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - immunology Autoantigens - drug effects Autoantigens - immunology Autoimmunity - drug effects Autoimmunity - immunology Case-Control Studies Cocaine - adverse effects Cocaine - immunology Cocaine-Related Disorders - immunology Dopamine Uptake Inhibitors - adverse effects Dopamine Uptake Inhibitors - immunology Enzyme-Linked Immunosorbent Assay Extracellular Traps - drug effects Extracellular Traps - immunology Extracellular Traps - metabolism Humans Immunoglobulin G - metabolism Levamisole - adverse effects Levamisole - immunology Neutrophils - drug effects Neutrophils - immunology Neutrophils - metabolism |
| Title | Neutrophil extracellular traps as a potential source of autoantigen in cocaine-associated autoimmunity |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/27354687 https://www.proquest.com/docview/1826708757 |
| Volume | 56 |
| WOSCitedRecordID | wos000398497700022&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8QwEA7qinjx_VhfRPAatk36yklEXDy4ZQ8Keytpk7BFaWsfiv_eSdrFkyAIpfTQhiYznflmMv0GoRvNIwluMiKa-R7xpMtJRF2PBFJLph3ta2m7ljyFcRwtFnw-JNyaoaxyZROtoZZlZnLkE4ODQ0u_flu9E9M1yuyuDi001tGIAZQxWh0uftjCfdd2sgZjQInDGF2xDnE2qZeqA0hoU9eTV_VJ_eB3jGl9zXT3v2-5h3YGlInverXYR2uqOEBbs2Ef_RDpWHVtXVbL_A2Dda6Fyd-bglQM11WDBRy4KltTSgTj9Bl-XGosurYEWRgKT5wXGKypgAGJGISspL0jtz-dtF9H6GX68Hz_SIaOCyRjzG-JqyBcUhC0OEr42gOskKUhldRRHCJBV0ovlFTyVPhuppwUkLkJ0KJQB0yEDKLsY7RRlIU6RThzmcgk56nhQAuUjAKHae4FWlKVSZeO0fVqBRPQaDNNUaiya5KfNRyjk14MSdVTbyQAtnwviMKzPzx9jrap8cG2zOYCjTR8z-oSbWYfbd7UV1ZV4BzPZ9-eT8xW |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Neutrophil+extracellular+traps+as+a+potential+source+of+autoantigen+in+cocaine-associated+autoimmunity&rft.jtitle=Rheumatology+%28Oxford%2C+England%29&rft.au=Lood%2C+Christian&rft.au=Hughes%2C+Grant+C&rft.date=2017-04-01&rft.eissn=1462-0332&rft.volume=56&rft.issue=4&rft.spage=638&rft_id=info:doi/10.1093%2Frheumatology%2Fkew256&rft_id=info%3Apmid%2F27354687&rft_id=info%3Apmid%2F27354687&rft.externalDocID=27354687 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1462-0332&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1462-0332&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1462-0332&client=summon |