Putative amino acid sequence of HLA-DRB chain contributing to rheumatoid arthritis susceptibility.

Watanabe, Yoshihisa; Tokunaga, Katsushi; Matsuki, Kazumasa; Takeuchi, Fujio; Matsuta, Kunio; Maeda, Hitoshi; Omoto, Keiichi; Juji, Takeo

doi:10.1084/jem.169.6.2263

Cited by 93 publications

(38 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…DRBl"0405, which was associated with arthritis in the present study, is known to be a susceptibility allele for rheumatoid arthritis in the Japanese population (10). Recent analyses by a British group have also shown that the development of rheumatoid arthritis in MCTD patients is associated with DR4 or DRI excluding DRBl"C1103 (11).…”

Section: Discussionsupporting

confidence: 62%

Clinical correlations with HLA type in Japanese patients with connective tissue disease and anti–U1 small nuclear RNP antibodies

Kuwana

Okano

Kaburaki

et al. 1996

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. To elucidate the roles of HLA genes in the clinical presentation of patients with connective tissue disease and serum anti-U1 small nuclear RNP antibody.Methods. HLA class I antigens and HLA class I1 alleles were determined in 43 Japanese patients with anti-U1 RNP antibody alone, by microcytotoxicity testing and DNA typing, respectively. Prospectively recorded clinical and laboratory features were analyzed in relation to HLA class I and class I1 types.Results. DQB1*0303 was associated with lupusrelated symptoms including fever, malar rash, oral ulcers, hypocomplementemia, and high-titer antidouble-stranded DNA antibody. Other HLA-clinical associations included DR2 with pleuritis, DR4 with hand swelling, and DRB1*0405 with arthritis.Conclusion. These HLA-clinical associations explain, in part, the heterogeneous clinical presentation in patients with anti-U1 RNP antibody.Autoantibody to U1 small nuclear RNP is a dominant feature of the autoimmune response that occurs in patients with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD) (1). However, the clinical presentation of patients with anti-U1 RNP antibody is variable; for example, some patients have SLE alone, but others have overlapping symptoms of systemic sclerosis (SSc) and myositis (1).Supported by the Scleroderma Grant for Intractable Disease from the Japanese Ministry of Health and Welfare, and grants-in-aid from the Ministry of Education, Science, and Culture, Japan.Masataka Kuwana, MD, Junichi Kaburaki, MD: Keio University School of Medicine, Tokyo, Japan; Yutaka Okano, MD: Nippon Kokan Hospital, Kawasaki, Japan; Hidetoshi Inoko, PhD: Tokai University School of Medicine, Isehara, Japan.Address reprint requests to Masataka Kuwana, MD, Division of Rheumatology, Department of Medicine, Keio University School of Medicine, 35 Shinano-machi; Shinjuku-ku, Tokyo 160, Japan.Submitted for publication November 20, 1995; accepted in revised form January 30, 1996. Despite efforts to explain this clinical heterogeneity in patients with anti-U1 RNP antibody based on immunoreactivities against individual U1 RNP constituent proteins (70K, A, B/B', and C ) or immunoglobulin allotypes, no strong and reproducible clinical associations with these markers have been reported except in the case of anti-70K reactivity, which is associated with Raynaud's phenomenon, sclerodactyly, hand swelling, telangiectasias, and abnormal esophageal motility (2).Recent molecular analyses of HLA class I1 genes have revealed associations between various antinuclear antibodies and polymorphisms of HLA (3). We have reported that immunoreactivities against individual U1 RNP constituent proteins as well as antibody titer were associated with several shared epitopes located on HLA-DR and D Q genes (4). In the present study, we sought HLA-clinical associations in Japanese patients with connective tissue disease and anti-U1 RNP antibody, to better define the role of HLA genes in the clinical presentation. PATIENTS AND METHODSPatients. Forty-three unrelated Ja...

show abstract

Section: Discussionsupporting

confidence: 62%

Clinical correlations with HLA type in Japanese patients with connective tissue disease and anti–U1 small nuclear RNP antibodies

Kuwana

Okano

Kaburaki

et al. 1996

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…The hypothesis is based on the sequence similarity of these DR alleles in the third hypervariable region of the DRP chain. Support for this hypothesis has also come from other recent studies of HLA alleles in RA patients (3)(4)(5)44). It is likely that this "epitope" influences binding of peptides to the antigen-binding site in these HLA-DR alleles.…”

Section: Discussionsupporting

confidence: 55%

Association of rheumatoid arthritis with a dominant DR1/Dw4/Dw14 sequence motif, but not with t cell receptor β chain gene alleles or haplotypes

Wallin

Hillert

Olerup

et al. 1991

Arthritis & Rheumatism

View full text Add to dashboard Cite

“…Thus, none of the 150 controls and only 3 of the 198 patients in the present study had "0404; none of our patients had the genotype DRBl "O4O1/*04O4. The most common DRBl allele in the present patient population was "0405, which was also identified in previous cross-sectional studies of Japanese RA patients (21,22). Since the amino acid sequence of the shared epitope of "0404 and "0405 is the same (QRRAA), it would be of interest to examine the contribution of the genotype of "0401/*0405 to the development of bonc erosions.…”

Section: Discussionmentioning

confidence: 92%

Lack of association of hla‐drb1 genotype with radiologic progression in japanese patients with early rheumatoid arthritis

Higami¹,

Hakoda²,

Matsuda³

et al. 1997

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. To evaluate the role of HLA-DRB1 genotypes in the development and progression of the rheumatoid arthritis (RA) disease process.Methods. Patients with polyarthritis of <1 year in duration were consecutively enrolled in the study. Other inclusion criteria were no diagnosis of inflammatory diseases other than RA, and no history of taking disease-modifying antirheumatic drugs or steroids. Patients were evaluated every 4 weeks, and radiographs of the handstwrists and feet were taken at presentation and 1 year later. HLA-DRB1 genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism methods.Results. We enrolled 198 patients (median disease duration 5.0 months) and 150 controls. The frequency of individuals with DRBl"O405 and "0410 was significantly higher in the patients than in the controls.Homozygous states for DRBl alleles with the RArelated shared epitope (SE) were associated with increased susceptibility for the development of polyarthritis (odds ratio 3.4, 95% confidence interval 1.5-7.7). None of the DRBl alleles or SE genotypes correlated with the presence of bone erosion at presentation or 1 year later.Conclusion. DRBl alleles with SEs were associated with the development of polyarthritis but not with early radiographic progression of the disease process.It is well established that certain HLA-DR alleles are associated with rheumatoid arthritis (RA) (1-3).

show abstract

Putative amino acid sequence of HLA-DRB chain contributing to rheumatoid arthritis susceptibility.

Cited by 93 publications

References 19 publications

Clinical correlations with HLA type in Japanese patients with connective tissue disease and anti–U1 small nuclear RNP antibodies

Clinical correlations with HLA type in Japanese patients with connective tissue disease and anti–U1 small nuclear RNP antibodies

Association of rheumatoid arthritis with a dominant DR1/Dw4/Dw14 sequence motif, but not with t cell receptor β chain gene alleles or haplotypes

Lack of association of hla‐drb1 genotype with radiologic progression in japanese patients with early rheumatoid arthritis

Contact Info

Product

Resources

About