ArticlePloS one2012
ACPA-negative RA consists of two genetically distinct subsets based on RF positivity in Japanese.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Anti-citrullinated peptide/protein antibody (ACPA)-negative RA shares a large proportion of susceptibility loci with ACPA-positive RA: a meta-analysis of genome-wide association study in a Japanese population.Arthritis research & therapy · 2015Pooled it
- A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.Human molecular genetics · 2013Pooled it
- Molecular Mimicry by the Tick-Borne Encephalitis Virus E Protein: A Hidden Link to Autoimmunity.International journal of molecular sciences · 2026Article
- Article
- Recent Advances in Research Regarding Autoantibodies in Connective Tissue Diseases and Related Disorders.Internal medicine (Tokyo, Japan) · 2019Review
- Independent association of HLA-DPB1*02:01 with rheumatoid arthritis in Japanese populations.PloS one · 2018Article
- Genetic landscape of interactive effects ofJournal of medical genetics · 2017Article
- Human Leukocyte Antigen-Disease Associations in Rheumatoid Arthritis.Rheumatic diseases clinics of North America · 2017Review
- Anti-centromere antibody exhibits specific distribution levels among anti-nuclear antibodies and may characterize a distinct subset in rheumatoid arthritis.Scientific reports · 2017Article
- Time-averaged disease activity fits better joint destruction in rheumatoid arthritis.Scientific reports · 2017Article
- The role of common protective alleles HLA-DRB1*13 among systemic autoimmune diseases.Genes and immunity · 2017Review
- Recent Advances in Defining the Genetic Basis of Rheumatoid Arthritis.Annual review of genomics and human genetics · 2016Review
- Article
- Rheumatoid Factor Is Associated With the Distribution of Hand Joint Destruction in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2015Article
- Human leukocyte antigen polymorphisms and personalized medicine for rheumatoid arthritis.Journal of human genetics · 2015Review
- The Spectrum and Clinical Significance of Autoantibodies in Rheumatoid Arthritis.Frontiers in immunology · 2015Review
- Association between CCR6 and rheumatoid arthritis: a meta-analysis.International journal of clinical and experimental medicine · 2015Article
- Article
- Serum anticyclic citrullinated protein antibody titers are correlated with the response to biological agents in patients with rheumatoid arthritis.Open access rheumatology : research and reviews · 2014Article
- Protective effect of the HLA-DRB1*13:02 allele in Japanese rheumatoid arthritis patients.PloS one · 2014Article
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Authors and funding
21 authors at 10 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HLA-DRB1, especially the shared epitope (SE), is strongly associated with rheumatoid arthritis (RA). However, recent studies have shown that SE is at most weakly associated with RA without anti-citrullinated peptide/protein antibody (ACPA). We have recently reported that ACPA-negative RA is associated with specific HLA-DRB1 alleles and diplotypes. Here, we attempted to detect genetically different subsets of ACPA-negative RA by classifying ACPA-negative RA patients into two groups based on their positivity for rheumatoid factor (RF). HLA-DRB1 genotyping data for totally 954 ACPA-negative RA patients and 2,008 healthy individuals in two independent sets were used. HLA-DRB1 allele and diplotype frequencies were compared among the ACPA-negative RF-positive RA patients, ACPA-negative RF-negative RA patients, and controls in each set. Combined results were also analyzed. A similar analysis was performed in 685 ACPA-positive RA patients classified according to their RF positivity. As a result, HLA-DRB1*04:05 and *09:01 showed strong associations with ACPA-negative RF-positive RA in the combined analysis (p = 8.8×10(-6) and 0.0011, OR: 1.57 (1.28-1.91) and 1.37 (1.13-1.65), respectively). We also found that HLA-DR14 and the HLA-DR8 homozygote were associated with ACPA-negative RF-negative RA (p = 0.00022 and 0.00013, OR: 1.52 (1.21-1.89) and 3.08 (1.68-5.64), respectively). These association tendencies were found in each set. On the contrary, we could not detect any significant differences between ACPA-positive RA subsets. As a conclusion, ACPA-negative RA includes two genetically distinct subsets according to RF positivity in Japan, which display different associations with HLA-DRB1. ACPA-negative RF-positive RA is strongly associated with HLA-DRB1*04:05 and *09:01. ACPA-negative RF-negative RA is associated with DR14 and the HLA-DR8 homozygote.
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