Anti-citrullinated peptide antibody-negative RA is a genetically distinct subset: a definitive study using only bone-erosive ACPA-negative rheumatoid arthritis.
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.
Ohmura
Koichiro
K
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
Terao
Chikashi
C
Maruya
Etsuko
E
Katayama
Masaki
M
Matoba
Kenichiro
K
Shimada
Kota
K
Murasawa
Akira
A
Honjo
Shigeru
S
Takasugi
Kiyoshi
K
Tohma
Shigeto
S
Matsuo
Keitaro
K
Tajima
Kazuo
K
Yukawa
Naoichiro
N
Kawabata
Daisuke
D
Nojima
Takaki
T
Fujii
Takao
T
Yamada
Ryo
R
Saji
Hiroo
H
Matsuda
Fumihiko
F
Mimori
Tsuneyo
T
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
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide