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. 1989 Jun 1;169(6):2263–2268. doi: 10.1084/jem.169.6.2263

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

PMCID: PMC2189339  PMID: 2732676

Abstract

The association between HLA-DR4 and rheumatoid arthritis (RA) has been established in many ethnic groups. To clarify the determinant of susceptibility to RA, a polymorphic segment of the HLA-DRB gene was amplified in vitro by polymerase chain reaction and analyzed with oligonucleotide probes specific for the HLA-DR4 DNA sequences. A particular sequence encoding amino acids Gln70-Arg71-Arg72-Ala73-Ala74 showed a strong association with RA (p less than 0.005, relative risk 6.0). This amino acid sequence occurs in the DRB molecules with three RA-associated specificities, DR4/Dw14, DR4/Dw15, and DR1. DR4/Dw4, which is common in Caucasian RA patients, has a strikingly similar amino acid sequence Gln70-Lys71-Arg72-Ala73-Ala74 in terms of polarity and charge profiles. Other RA nonassociated sequences differ from this sequence by at least one amino acid substitution that causes the change of the net charge. The composition of amino acid residues at the positions 70-74 may play a crucial role in the pathogenesis of RA.

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Selected References

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  1. Brown J. H., Jardetzky T., Saper M. A., Samraoui B., Bjorkman P. J., Wiley D. C. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature. 1988 Apr 28;332(6167):845–850. doi: 10.1038/332845a0. [DOI] [PubMed] [Google Scholar]
  2. Cairns J. S., Curtsinger J. M., Dahl C. A., Freeman S., Alter B. J., Bach F. H. Sequence polymorphism of HLA DR beta 1 alleles relating to T-cell-recognized determinants. Nature. 1985 Sep 12;317(6033):166–168. doi: 10.1038/317166a0. [DOI] [PubMed] [Google Scholar]
  3. Duquesnoy R. J., Marrari M., Hackbarth S., Zeevi A. Serological and cellular definition of a new HLA-DR associated determinant, MC1, and its association with rheumatoid arthritis. Hum Immunol. 1984 Jul;10(3):165–176. doi: 10.1016/0198-8859(84)90037-5. [DOI] [PubMed] [Google Scholar]
  4. Gibofsky A., Winchester R. J., Patarroyo M., Fotino M., Kunkel H. G. Disease associations of the Ia-like human alloantigens. Contrasting patterns in rheumatoid arthritis and systemic lupus erythematosus. J Exp Med. 1978 Dec 1;148(6):1728–1732. doi: 10.1084/jem.148.6.1728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gregersen P. K., Shen M., Song Q. L., Merryman P., Degar S., Seki T., Maccari J., Goldberg D., Murphy H., Schwenzer J. Molecular diversity of HLA-DR4 haplotypes. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2642–2646. doi: 10.1073/pnas.83.8.2642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gregersen P. K., Silver J., Winchester R. J. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987 Nov;30(11):1205–1213. doi: 10.1002/art.1780301102. [DOI] [PubMed] [Google Scholar]
  7. Harvey J., Lotze M., Arnett F. C., Bias W. B., Billingsley L. M., Harvey E., Hsu S. H., Sutton J. D., Zizic T. M., Stevens M. B. Rheumatoid arthritis in a Chippewa band. II. Field study with clinical serologic and HLA-D correlations. J Rheumatol. 1983 Feb;10(1):28–32. [PubMed] [Google Scholar]
  8. Karr R. W., Rodey G. E., Lee T., Schwartz B. D. Association of HLA-DRw4 with rheumatoid arthritis in black and white patients. Arthritis Rheum. 1980 Nov;23(11):1241–1245. doi: 10.1002/art.1780231102. [DOI] [PubMed] [Google Scholar]
  9. Maeda H., Juji T., Mitsui H., Sonozaki H., Okitsu K. HLA DR4 and rheumatoid arthritis in Japanese people. Ann Rheum Dis. 1981 Jun;40(3):299–302. doi: 10.1136/ard.40.3.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. McMichael A. J., Sasazuki T., McDevitt H. O., Payne R. O. Increased frequency of HLA-Cw3 and HLA-Dw4 in rheumatoid arthritis. Arthritis Rheum. 1977 Jun;20(5):1037–1042. doi: 10.1002/art.1780200501. [DOI] [PubMed] [Google Scholar]
  11. Merryman P., Gregersen P. K., Lee S., Silver J., Nuñez-Roldan A., Crapper R., Winchester R. Nucleotide sequence of a DRw10 beta chain cDNA clone. Identity of the third D region with that of the DRw53 allele of the beta 2 locus and as the probable site encoding a polymorphic MHC class II epitope. J Immunol. 1988 Apr 1;140(7):2447–2452. [PubMed] [Google Scholar]
  12. Nakai Y., Wakisaka A., Aizawa M., Itakura K., Nakai H., Ohashi A. HLA and rheumatoid arthritis in the Japanese. Arthritis Rheum. 1981 May;24(5):722–725. doi: 10.1002/art.1780240516. [DOI] [PubMed] [Google Scholar]
  13. Nehra N. K., Vaidya M. C., Taneja V., Agarwal A., Malaviya A. N. HLA-DR antigens in rheumatoid arthritis in North India. Tissue Antigens. 1982 Oct;20(4):300–302. doi: 10.1111/j.1399-0039.1982.tb00360.x. [DOI] [PubMed] [Google Scholar]
  14. Nepom G. T., Seyfried C. E., Holbeck S. L., Wilske K. R., Nepom B. S. Identification of HLA-Dw14 genes in DR4+ rheumatoid arthritis. Lancet. 1986 Nov 1;2(8514):1002–1005. doi: 10.1016/s0140-6736(86)92614-0. [DOI] [PubMed] [Google Scholar]
  15. Saiki R. K., Bugawan T. L., Horn G. T., Mullis K. B., Erlich H. A. Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele-specific oligonucleotide probes. Nature. 1986 Nov 13;324(6093):163–166. doi: 10.1038/324163a0. [DOI] [PubMed] [Google Scholar]
  16. Sasazuki T., Kaneoka H., Ohta N., Hayase R., Iwamoto I. Four common HLA haplotypes and their association with diseases in the Japanese population. Transplant Proc. 1979 Dec;11(4):1871–1873. [PubMed] [Google Scholar]
  17. Schiff B., Mizrachi Y., Orgad S., Yaron M., Gazit E. Association of HLA-Aw31 and HLA-DR1 with adult rheumatoid arthritis. Ann Rheum Dis. 1982 Aug;41(4):403–404. doi: 10.1136/ard.41.4.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Stastny P. Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. N Engl J Med. 1978 Apr 20;298(16):869–871. doi: 10.1056/NEJM197804202981602. [DOI] [PubMed] [Google Scholar]
  19. Todd J. A., Acha-Orbea H., Bell J. I., Chao N., Fronek Z., Jacob C. O., McDermott M., Sinha A. A., Timmerman L., Steinman L. A molecular basis for MHC class II--associated autoimmunity. Science. 1988 May 20;240(4855):1003–1009. doi: 10.1126/science.3368786. [DOI] [PubMed] [Google Scholar]
  20. Todd J. A., Bell J. I., McDevitt H. O. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature. 1987 Oct 15;329(6140):599–604. doi: 10.1038/329599a0. [DOI] [PubMed] [Google Scholar]
  21. Ueno Y., Iwaki Y., Terasaki P. I., Park M. S., Barnett E. V., Chia D., Nakata S. HLA-DR4 in Negro and Mexican rheumatoid arthritis patients. J Rheumatol. 1981 Sep-Oct;8(5):804–807. [PubMed] [Google Scholar]

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