HLA-DR genotype risks in seropositive rheumatoid arthritis.

We studied the distribution of HLA-A, B, C, and -DR antigens in 77 Caucasian patients with sero-positive rheumatoid arthritis. Forty-four patients were genotyped and compared with the control panel of 110 unrelated Caucasian genotyped donors. The data obtained confirm the association of DR4 with RA, and reveal an increased risk of disease for patients carrying DR1, DR2, and DR3, compared to the risk for those carrying other antigens, such as DR5, DRw6, and DR7. There is a higher risk for DR4/4 homozygotes than for DR4/1, DR4/2, or DR4/3 heterozygotes. DR4/5, DR4/6, and DR4/7 have a lower risk than the previously mentioned genotypes. The genotype risks are compatible with the inheritance of a single, linked genetic determinant of disease susceptibility, but we are unable to distinguish between recessive and dominant inheritance of susceptibility using the "antigen-frequencies-amongst-diseases" method. DR4 seems to be more frequent in patients in whom onset occurs before the age of 35 (79% vs. 54% DR4 positive). A significant excess of DR3 + is observed in patients with toxic complications following treatment with gold salts (X2(1) = 8.96).

[1]  G. Lathrop Estimating genotype relative risks. , 2008, Tissue antigens.

[2]  J. Dausset,et al.  HLA system and side effects of gold salts and D-penicillamine treatment of rheumatoid arthritis. , 1982, Annals of the rheumatic diseases.

[3]  S. Britton EBV and rheumatoid arthritis. , 1982, Immunology today.

[4]  A. Steinberg,et al.  Defective EBV-specific suppressor T-cell function in rheumatoid arthritis. , 1981, The New England journal of medicine.

[5]  N. Zvaifler,et al.  Impaired regulation of Epstein-Barr virus-induced lymphocyte proliferation in rheumatoid arthritis is due to a T cell defect. , 1981, Journal of immunology.

[6]  E. Möller,et al.  HLA and rheumatoid arthritis. A study of five families. , 1981, Tissue antigens.

[7]  W. Braun,et al.  Clinical and HLA studies in multiple case families with rheumatoid arthritis. , 1981, Tissue antigens.

[8]  A. Svejgaard,et al.  HLA genotype distribution and genetic models of insulin‐dependent diabetes mellitus , 1981, Annals of human genetics.

[9]  J. Woodrow,et al.  HLA DR ANTIGENS IN INDIAN PATIENTS WITH RHEUMATOID ARTHRITIS , 1981, The Lancet.

[10]  P. Rubinstein The effect of association of genetic factors on relative risk , 1980, Annals of human genetics.

[11]  M. Corbett,et al.  HLA-D and DR determinants in rheumatoid arthritis. , 1979, Transplantation proceedings.

[12]  R. Winchester,et al.  Disease associations of the Ia-like human alloantigens. Contrasting patterns in rheumatoid arthritis and systemic lupus erythematosus , 1978, The Journal of experimental medicine.

[13]  G. Panayi,et al.  B lymphocyte alloantigens in the study of the genetic basis of rheumatoid arthritis. , 1977, Annals of the rheumatic diseases.

[14]  H. Mcdevitt,et al.  Increased frequency of HLA-Cw3 and HLA-Dw4 in rheumatoid arthritis. , 1977, Arthritis and rheumatism.

[15]  M. Kupperman Linear Statistical Inference and Its Applications 2nd Edition (C. Radhakrishna Rao) , 1975 .

[16]  G. A. Bennett,et al.  1958 Revision of diagnostic criteria for rheumatoid arthritis. , 1959, Bulletin on the rheumatic diseases.

[17]  G. Alarcón,et al.  Seronegative rheumatoid arthritis. A distinct immunogenetic disease? , 1982, Arthritis and rheumatism.

[18]  P. Wernet,et al.  Genetic Analysis of Rheumatoid Arthritis: Population and Family Studies , 1981 .

[19]  J. Smolen,et al.  Rheumatoid arthritis and B lymphocyte alloantigen HLA-DRw4. , 1980, The Journal of rheumatology.

[20]  S. Ferrone,et al.  Enhancement of sheep red blood cell human lymphocyte rosette formation by the sulfhydryl compound 2-amino ethylisothiouronium bromide. , 1975, Clinical immunology and immunopathology.