title: Anti-citrullinated peptide antibody-negative RA is a genetically distinct subset: a definitive study using only bone-erosive ACPA-negative rheumatoid arthritis.
abstract: OBJECTIVE
  ACPA is a highly specific marker for RA. It was recently reported that ACPA can be used to classify RA into two disease subsets, ACPA-positive and ACPA-negative RA. ACPA-positive RA was found to be associated with the HLA-DR shared epitope (SE), but ACPA negative was not. However, the suspicion remained that this result was caused by the ACPA-negative RA subset containing patients with non-RA diseases. We examined whether this is the case even when possible non-RA ACPA-negative RA patients were excluded by selecting only patients with bone erosion.
  
  
  METHODS
  We genotyped HLA-DRB1 alleles for 574 ACPA-positive RA, 185 ACPA-negative RA (including 97 erosive RA) and 1508 healthy donors. We also tested whether HLA-DR SE is associated with RF-negative or ANA-negative RA.
  
  
  RESULTS
  ACPA-negative RA with apparent bone erosion was not associated with SE, supporting the idea that ACPA-negative RA is genetically distinct from ACPA-positive RA. We also tested whether these subsets are based on autoantibody-producing activity. In accordance with the ACPA-negative RA subset, the RF-negative RA subset showed a clearly distinct pattern of association with SE from the RF-positive RA. In contrast, ANA-negative as well as ANA-positive RA was similarly associated with SE, suggesting that the subsets distinguished by ACPA are not based simply on differences in autoantibody production.
  
  
  CONCLUSIONS
  ACPA-negative erosive RA is genetically distinct from ACPA-positive RA.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho Sakyo-ku, Kyoto 606-8507, Japan. ohmurako@kuhp.kyoto-u.ac.jp
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohmura
authors.forename: Chikashi
authors.initials: C
authors.lastname: Terao
authors.forename: Etsuko
authors.initials: E
authors.lastname: Maruya
authors.forename: Masaki
authors.initials: M
authors.lastname: Katayama
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Matoba
authors.forename: Kota
authors.initials: K
authors.lastname: Shimada
authors.forename: Akira
authors.initials: A
authors.lastname: Murasawa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Honjo
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takasugi
authors.forename: Shigeto
authors.initials: S
authors.lastname: Tohma
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima
authors.forename: Naoichiro
authors.initials: N
authors.lastname: Yukawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kawabata
authors.forename: Takaki
authors.initials: T
authors.lastname: Nojima
authors.forename: Takao
authors.initials: T
authors.lastname: Fujii
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamada
authors.forename: Hiroo
authors.initials: H
authors.lastname: Saji
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Tsuneyo
authors.initials: T
authors.lastname: Mimori
mesh_terms: D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000145:classification / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000235:genetics* / Q000276:immunology; D015415:Biomarkers; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000235:genetics* / Q000276:immunology; D013223:Statistics as Topic
chemical_list: D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide