title: Genes, environment and immunity in the development of rheumatoid arthritis.
abstract: The combined role of genes, environment and immunity in the development of rheumatoid arthritis (RA) has been the subject of recent investigations. New data support a gene-environment interaction between smoking and the MHC class II HLA-DRB1 shared epitope (SE) genes in anti-citrulline antibody (anti-CP(+)) RA but not in anti-CP(-) disease. These data from genetic epidemiology, together with information on citrullination in the lungs of smokers, have prompted the formulation of a new etiological hypothesis for anti-CP(+) RA, suggesting that smoking in the context of HLA-DR SE might trigger immunity to citrulline-modified proteins and that this immunity, after several years, might cause arthritis.
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden. lars.klareskog@ki.se
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov
authors.forename: Johan
authors.initials: J
authors.lastname: Rönnelid
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology*; D004781:Environmental Exposure / Q000009:adverse effects*; D020022:Genetic Predisposition to Disease; D006801:Humans