title: Chronic smoke exposure induces rheumatoid factor and anti-heat shock protein 70 autoantibodies in susceptible mice and humans with lung disease.
abstract: The impact of cigarette smoke (CS), a risk factor for rheumatoid arthritis (RA), on sauto-antibody production was studied in humans and mice with and without chronic lung disease (LD). Rheumatoid factor (RF), anti-cyclic citrullinated peptides (CCPs), and anti-HSP70 autoantibodies were measured in several mouse strains and in cohorts of smokers and nonsmokers with and without autoimmune disease. Chronic smoking-induced RFs in AKR/J mice, which are most susceptible to LD. RFs were identified in human smokers, preferentially in those with LD. Anti-HSP70 auto-antibodies were identified in CS-exposed AKR/J mice but not in ambient air exposed AKR/J controls. Whereas inflammation could induce anti-HSP70 IgM, smoke exposure promoted the switch to anti-HSP70 IgG autoantibodies. Elevated anti-CCP autoantibodies were not detected in CS-exposed mice or smokers. AKR/J splenocytes stimulated in vitro by immune complexes (ICs) of HSP70/anti-HSP70 antibodies produced RFs. The CD91 scavenger pathway was required as anti-CD91 blocked the HSP70-IC-induced RF response. Blocking Toll-like receptors did not influence the HSP70-IC-induced RFs. These studies identify both anti-HSP70 and RFs as serological markers of smoke-related LD in humans and mice. Identification of these autoantibodies could suggest a common environmental insult, namely CS, in a number of different disease settings.
authors.affiliation: Department of Medicine, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada. Marianna.newkirk@mcgill.ca
authors.forename: Marianna M
authors.initials: MM
authors.lastname: Newkirk
authors.forename: Simeon
authors.initials: S
authors.lastname: Mitchell
authors.forename: Michael
authors.initials: M
authors.lastname: Procino
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Li
authors.forename: Manuel
authors.initials: M
authors.lastname: Cosio
authors.forename: Witold
authors.initials: W
authors.lastname: Mazur
authors.forename: Vuokko L
authors.initials: VL
authors.lastname: Kinnula
authors.forename: Marie
authors.initials: M
authors.lastname: Hudson
authors.forename: Murray
authors.initials: M
authors.lastname: Baron
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Fritzler
authors.forename: Hani S
authors.initials: HS
authors.lastname: El-Gabalawy
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000037:antagonists & inhibitors / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D012217:Rheumatoid Factor / Q000097:blood / Q000276:immunology*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D014028:Tobacco Smoke Pollution; D012217:Rheumatoid Factor