Skip to main content
NCBI home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1989 Apr;48(4):295–301. doi: 10.1136/ard.48.4.295

HLA class II DR, DQ, and DP restriction fragment length polymorphisms in rheumatoid arthritis.

W M Howell 1, P R Evans 1, P J Wilson 1, M I Cawley 1, J L Smith 1
PMCID: PMC1003744  PMID: 2565707

Abstract

HLA class II restriction fragment length polymorphisms (RFLPs) were studied in 43 individuals with established seropositive rheumatoid arthritis (RA) and in a group of healthy controls. All patients and controls were tissue typed for HLA-A, B, and DR antigens. Rapid, initial screening for RA associated RFLPs was conducted by pooling DNA samples from 11 HLA-DR4 positive patients with RA and comparing the RFLP patterns with those seen in a pool of DNA samples drawn from 11 HLA-DR4 positive healthy controls. Candidate RA associated RFLPs were examined in our full panel of patients with RA and controls. In most cases the RFLPs detected showed no significant association with RA. An exception was a 13.0 kb DraI DQ beta associated RFLP, which, when HLA-DR4 positive patients with RA and controls were considered alone, showed a weak positive association with susceptibility to RA. This RFLP was not associated with known DR, DQ, or Dw specificities. These results show a distinct paucity of class II RA associated RFLPs but may indicate a role for DQ beta genetic variation in the aetiology of RA.

Full text

PDF
295

Images in this article

297Image
on p.297
297Image
on p.297
298Image
on p.298
299Image
on p.299
299Image
on p.299

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnheim N., Strange C., Erlich H. Use of pooled DNA samples to detect linkage disequilibrium of polymorphic restriction fragments and human disease: studies of the HLA class II loci. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6970–6974. doi: 10.1073/pnas.82.20.6970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Auffray C., Lillie J. W., Arnot D., Grossberger D., Kappes D., Strominger J. L. Isotypic and allotypic variation of human class II histocompatibility antigen alpha-chain genes. Nature. 1984 Mar 22;308(5957):327–333. doi: 10.1038/308327a0. [DOI] [PubMed] [Google Scholar]
  3. Bidwell J. L., Jarrold E. A. HLA-DR allogenotyping using exon-specific cDNA probes and application of rapid minigel methods. Mol Immunol. 1986 Oct;23(10):1111–1116. doi: 10.1016/0161-5890(86)90009-x. [DOI] [PubMed] [Google Scholar]
  4. Bodmer W. F. The HLA system: structure and function. J Clin Pathol. 1987 Sep;40(9):948–958. doi: 10.1136/jcp.40.9.948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Böhme J., Carlsson B., Wallin J., Möller E., Persson B., Peterson P. A., Rask L. Only one DQ-beta restriction fragment pattern of each DR specificity is associated with insulin-dependent diabetes. J Immunol. 1986 Aug 1;137(3):941–947. [PubMed] [Google Scholar]
  6. Erlich H., Stetler D., Sheng-Dong R., Saiki R. Analysis by molecular cloning of the human class II genes. Fed Proc. 1984 Dec;43(15):3025–3030. [PubMed] [Google Scholar]
  7. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  8. Howell M. D., Austin R. K., Kelleher D., Nepom G. T., Kagnoff M. F. An HLA-D region restriction fragment length polymorphism associated with celiac disease. J Exp Med. 1986 Jul 1;164(1):333–338. doi: 10.1084/jem.164.1.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Inoko H., Ando A., Tsuji K., Matsuki K., Juji T., Honda Y. HLA-DQ beta chain DNA restriction fragments can differentiate between healthy and narcoleptic individuals with HLA-DR2. Immunogenetics. 1986;23(2):126–128. doi: 10.1007/BF00377973. [DOI] [PubMed] [Google Scholar]
  10. Jaraquemada D., Ollier W., Awad J., Young A., Silman A., Roitt I. M., Corbett M., Hay F., Cosh J. A., Maini R. N. HLA and rheumatoid arthritis: a combined analysis of 440 British patients. Ann Rheum Dis. 1986 Aug;45(8):627–636. doi: 10.1136/ard.45.8.627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Larhammar D., Schenning L., Gustafsson K., Wiman K., Claesson L., Rask L., Peterson P. A. Complete amino acid sequence of an HLA-DR antigen-like beta chain as predicted from the nucleotide sequence: similarities with immunoglobulins and HLA-A, -B, and -C antigens. Proc Natl Acad Sci U S A. 1982 Jun;79(12):3687–3691. doi: 10.1073/pnas.79.12.3687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Marcadet A., Gebuhrer L., Betuel H., Seignalet J., Freidel A. C., Confavreux C., Billiard M., Dausset J., Cohen D. DNA polymorphism related to HLA-DR2 Dw2 in patients with narcolepsy. Immunogenetics. 1985;22(6):679–683. doi: 10.1007/BF00430317. [DOI] [PubMed] [Google Scholar]
  13. Michelsen B., Lernmark A. Molecular cloning of a polymorphic DNA endonuclease fragment associates insulin-dependent diabetes mellitus with HLA-DQ. J Clin Invest. 1987 Apr;79(4):1144–1152. doi: 10.1172/JCI112931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nepom G. T., Hansen J. A., Nepom B. S. The molecular basis for HLA class II associations with rheumatoid arthritis. J Clin Immunol. 1987 Jan;7(1):1–7. doi: 10.1007/BF00915418. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Nunez G., Moore S. E., Ball G. V., Hurd E. R., Stastny P. Study of HLA antigens in ten multiple-case rheumatoid arthritis families. J Rheumatol. 1984 Apr;11(2):129–135. [PubMed] [Google Scholar]
  17. Pawelec G., Reekers P., Brackertz D., Sansom D., Schneider E. M., Blaurock M., Müller C., Rehbein A., Balko I., Wernet P. HLA-DP in rheumatoid arthritis. Tissue Antigens. 1988 Feb;31(2):83–89. doi: 10.1111/j.1399-0039.1988.tb02068.x. [DOI] [PubMed] [Google Scholar]
  18. Payami H., Thomson G., Khan M. A., Grennan D. M., Sanders P., Dyer P., Dostal C. Genetics of rheumatoid arthritis. Tissue Antigens. 1986 Feb;27(2):57–63. doi: 10.1111/j.1399-0039.1986.tb01499.x. [DOI] [PubMed] [Google Scholar]
  19. Roux-Dosseto M., Auffray C., Lillie J. W., Boss J. M., Cohen D., DeMars R., Mawas C., Seidman J. G., Strominger J. L. Genetic mapping of a human class II antigen beta-chain cDNA clone to the SB region of the HLA complex. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6036–6040. doi: 10.1073/pnas.80.19.6036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sachs J. A., Kirwan J. R. Multiple HLA associations and disease susceptibility. Dis Markers. 1986 Jun;4(1-2):13–17. [PubMed] [Google Scholar]
  21. Sansom D. M., Bidwell J. L., Maddison P. J., Campion G., Klouda P. T., Bradley B. A. HLA DQ alpha and DQ beta restriction fragment length polymorphisms associated with Felty's syndrome and DR4-positive rheumatoid arthritis. Hum Immunol. 1987 Aug;19(4):269–278. doi: 10.1016/0198-8859(87)90044-9. [DOI] [PubMed] [Google Scholar]
  22. Singal D. P., D'Souza M., Reid B., Bensen W. G., Kassam Y. B., Adachi J. D. HLA-DQ beta-chain polymorphism in HLA-DR4 haplotypes associated with rheumatoid arthritis. Lancet. 1987 Nov 14;2(8568):1118–1120. doi: 10.1016/s0140-6736(87)91548-0. [DOI] [PubMed] [Google Scholar]
  23. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Szafer F., Brautbar C., Tzfoni E., Frankel G., Sherman L., Cohen I., Hacham-Zadeh S., Aberer W., Tappeiner G., Holubar K. Detection of disease-specific restriction fragment length polymorphisms in pemphigus vulgaris linked to the DQw1 and DQw3 alleles of the HLA-D region. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6542–6545. doi: 10.1073/pnas.84.18.6542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES