title: Is rheumatoid arthritis an autoimmune disease?
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is not a homogenous disease entity but a syndrome with different causes and abnormalities with shared clinical manifestations. One major subset is anticitrullinated protein antibody (ACPA)-positive RA, which represents the larger fraction of RA patients and where autoantibodies and HLA class II association implicate an autoimmune condition. In the past few years, the specificity of the ACPA response and the possibility to subdivide patients based on ACPA subgroups have received much attention whereas the effector functions of the autoantibodies and underlying lymphocytes have not.
  
  
  RESULTS
  The review, based on HLA, will discuss the generation of the autoreactive citrulline-specific T-cell repertoire, highlight our current understanding of T-cell specificities and effector functions of both the T cells and ACPAs.
  
  
  CONCLUSIONS
  Dividing RA into subsets has only influenced clinical practice to a limited degree, that is, by indicating a better response to therapies modulating adaptive immunity, such as rituximab, in the ACPA+ disease subset. A more detailed understanding of the immune reactions underlying various subsets of RA may, however, change our view on RA therapeutics and prevention with the assumption that autoimmune variants of RA should be both curable and preventable.
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Karine
authors.initials: K
authors.lastname: Chemin
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Vivianne
authors.initials: V
authors.lastname: Malmström
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002956:Citrulline / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D001323:Autoantibodies; D002956:Citrulline