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Rheumatoid factor (RF<\/jats:styled-content>), anti\u2010cyclic citrullinated peptides (CCP<\/jats:styled-content>s), and anti\u2010HSP<\/jats:styled-content>70 autoantibodies were measured in several mouse strains and in cohorts of smokers and nonsmokers with and without autoimmune disease. Chronic smoking\u2010induced RF<\/jats:styled-content>s in AKR<\/jats:styled-content>\/J<\/jats:styled-content> mice, which are most susceptible to LD<\/jats:styled-content>. RF<\/jats:styled-content>s were identified in human smokers, preferentially in those with LD<\/jats:styled-content>. Anti\u2010HSP<\/jats:styled-content>70 auto\u2010antibodies were identified in CS<\/jats:styled-content>\u2010exposed AKR<\/jats:styled-content>\/J<\/jats:styled-content> mice but not in ambient air exposed AKR\/J controls. Whereas inflammation could induce anti\u2010HSP<\/jats:styled-content>70 I<\/jats:styled-content>gM<\/jats:styled-content>, smoke exposure promoted the switch to anti\u2010HSP<\/jats:styled-content>70 I<\/jats:styled-content>gG<\/jats:styled-content> autoantibodies. Elevated anti\u2010CCP<\/jats:styled-content> autoantibodies were not detected in CS<\/jats:styled-content>\u2010exposed mice or smokers. AKR<\/jats:styled-content>\/J<\/jats:styled-content> splenocytes stimulated in vitro by immune complexes (IC<\/jats:styled-content>s) of HSP<\/jats:styled-content>70\/anti\u2010HSP<\/jats:styled-content>70 antibodies produced RF<\/jats:styled-content>s. The CD<\/jats:styled-content>91 scavenger pathway was required as anti\u2010CD<\/jats:styled-content>91 blocked the HSP<\/jats:styled-content>70\u2010IC<\/jats:styled-content>\u2010induced RF<\/jats:styled-content> response. Blocking T<\/jats:styled-content>oll\u2010like receptors did not influence the HSP<\/jats:styled-content>70\u2010IC<\/jats:styled-content>\u2010induced RF<\/jats:styled-content>s. These studies identify both anti\u2010HSP<\/jats:styled-content>70 and RF<\/jats:styled-content>s as serological markers of smoke\u2010related LD<\/jats:styled-content> in humans and mice. Identification of these autoantibodies could suggest a common environmental insult, namely CS<\/jats:styled-content>, in a number of different disease settings.<\/jats:p>","DOI":"10.1002\/eji.201141856","type":"journal-article","created":{"date-parts":[[2012,4,25]],"date-time":"2012-04-25T00:14:07Z","timestamp":1335312847000},"page":"1051-1061","source":"Crossref","is-referenced-by-count":37,"title":["Chronic smoke exposure induces rheumatoid factor and anti\u2010heat shock protein 70 autoantibodies in susceptible mice and humans with lung disease"],"prefix":"10.1002","volume":"42","author":[{"given":"Marianna M.","family":"Newkirk","sequence":"first","affiliation":[{"name":"Department of Medicine Research Institute of the McGill University Health Centre Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simeon","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Medicine Research Institute of the McGill University Health Centre Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Procino","sequence":"additional","affiliation":[{"name":"Department of Medicine Research Institute of the McGill University Health Centre Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine Research Institute of the McGill University Health Centre Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Cosio","sequence":"additional","affiliation":[{"name":"Department of Medicine Research Institute of the McGill University Health Centre Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Witold","family":"Mazur","sequence":"additional","affiliation":[{"name":"Department of Medicine Pulmonary Division, Helsinki University Central Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vuokko L.","family":"Kinnula","sequence":"additional","affiliation":[{"name":"Department of Medicine Pulmonary Division, Helsinki University Central Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Hudson","sequence":"additional","affiliation":[{"name":"Department of Medicine Jewish General Hospital McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray","family":"Baron","sequence":"additional","affiliation":[{"name":"Department of Medicine Jewish General Hospital McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin J.","family":"Fritzler","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani S.","family":"El\u2010Gabalawy","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Manitoba Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,4,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2005.09.053"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2751"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458509345907"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.02.019"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep383"},{"key":"e_1_2_7_7_1","first-page":"1145","article-title":"Arthritis in Aboriginal Manitobans: evidence for a high burden of disease","volume":"35","author":"Barnabe C.","year":"2008","journal-title":"J. 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