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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1990 Aug;49(8):578–581. doi: 10.1136/ard.49.8.578

Associations between HLA and antibodies to collagen in rheumatoid arthritis.

M J Rowley 1, B Tait 1, T Doran 1, P Emery 1, I R Mackay 1
PMCID: PMC1004167  PMID: 2396861

Abstract

Associations between HLA types and serum antibodies to native and denatured type II collagen were sought in 105 patients with rheumatoid arthritis (RA). Antibodies were measured using a solid phase radioimmunoassay. There were no significant associations between any HLA antigen (A, B, or DR) and a high antibody titre to native collagen. There were significant associations, however, between HLA antigens and high antibody titres to denatured collagen. Although DR4 did not show an association, the phenotype A2+DR4+ did; this was not related to A2 as A2+DR- was not associated with a high antibody titre. No single B locus antigen showed an association, but several B locus antigens, B12, B15, and B40, were included in phenotypes with A2 and DR4 which were associated with a high antibody titre to denatured collagen. These HLA associations with anticollagen type II are best explained by a gene other than DR4 (but in linkage with it) which may regulate the antibody response to denatured collagen. If so, this would represent an HLA gene in addition to DR4 that is active in RA.

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Selected References

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

  1. Banerjee S., Luthra H. S., Moore S. B., O'Fallon W. M. Serum IgG anti-native type II collagen antibodies in rheumatoid arthritis: association with HLA DR4 and lack of clinical correlation. Clin Exp Rheumatol. 1988 Oct-Dec;6(4):373–380. [PubMed] [Google Scholar]
  2. Choi E. K., Gatenby P. A., McGill N. W., Bateman J. F., Cole W. G., York J. R. Autoantibodies to type II collagen: occurrence in rheumatoid arthritis, other arthritides, autoimmune connective tissue diseases, and chronic inflammatory syndromes. Ann Rheum Dis. 1988 Apr;47(4):313–322. doi: 10.1136/ard.47.4.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clague R. B., Shaw M. J., Holt P. J. Incidence of serum antibodies to native type I and type II collagens in patients with inflammatory arthritis. Ann Rheum Dis. 1980 Jun;39(3):201–206. doi: 10.1136/ard.39.3.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Collier D. H., Kerwar S. S., Garovoy M. R., Fye K. H., Stobo J. D. Anticollagen antibodies and immune response gene products in rheumatoid arthritis. Arthritis Rheum. 1984 Nov;27(11):1201–1209. doi: 10.1002/art.1780271101. [DOI] [PubMed] [Google Scholar]
  5. Dyer P. A., Clague R. B., Klouda P. T., Firth S., Harris R., Holt P. J. HLA antigens in patients with rheumatoid arthritis and antibodies to native type II collagen. Tissue Antigens. 1982 Nov;20(5):394–396. doi: 10.1111/j.1399-0039.1982.tb02256.x. [DOI] [PubMed] [Google Scholar]
  6. Goronzy J., Weyand C. M., Fathman C. G. Shared T cell recognition sites on human histocompatibility leukocyte antigen class II molecules of patients with seropositive rheumatoid arthritis. J Clin Invest. 1986 Mar;77(3):1042–1049. doi: 10.1172/JCI112358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Holmdahl R., Klareskog L., Andersson M., Hansen C. High antibody response to autologous type II collagen is restricted to H-2q. Immunogenetics. 1986;24(2):84–89. doi: 10.1007/BF00373114. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Klimiuk P. S., Clague R. B., Grennan D. M., Dyer P. A., Smeaton I., Harris R. Autoimmunity to native type II collagen--a distinct genetic subset of rheumatoid arthritis. J Rheumatol. 1985 Oct;12(5):865–870. [PubMed] [Google Scholar]
  10. Klouda P. T., Bidwell J. L., Bodmer J. G., Wasik A., Maddison P. J. A possible haplotype association in Felty's syndrome. Dis Markers. 1986 Jun;4(1-2):27–28. [PubMed] [Google Scholar]
  11. Mackay I. R., Tait B. D. HLA associations with autoimmune-type chronic active hepatitis: identification of B8-DRw3 haplotype by family studies. Gastroenterology. 1980 Jul;79(1):95–98. [PubMed] [Google Scholar]
  12. Ohta N., Nishimura Y. K., Tanimoto K., Horiuchi Y., Abe C., Shiokawa Y., Abe T., Katagiri M., Yoshiki T., Sasazuki T. Association between HLA and Japanese patients with rheumatoid arthritis. Hum Immunol. 1982 Oct;5(2):123–132. doi: 10.1016/0198-8859(82)90057-x. [DOI] [PubMed] [Google Scholar]
  13. Ollier W., Venables P. J., Mumford P. A., Maini R. N., Awad J., Jaraquemada D., D'Amaro J., Festenstein H. HLA antigen associations with extra-articular rheumatoid arthritis. Tissue Antigens. 1984 Nov;24(5):279–291. doi: 10.1111/j.1399-0039.1984.tb02139.x. [DOI] [PubMed] [Google Scholar]
  14. Panayi G. S., Wooley P., Batchelor J. R. Genetic basis of rheumatoid disease: HLA antigens, disease manifestations, and toxic reactions to drugs. Br Med J. 1978 Nov 11;2(6148):1326–1328. doi: 10.1136/bmj.2.6148.1326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Puttick A., Briggs D., Welsh K., Jacoby R., Williamson E., Jones V. Extended haplotypes in rheumatoid arthritis and preliminary evidence for an interaction with immunoglobulin genes. Dis Markers. 1986 Jun;4(1-2):139–144. [PubMed] [Google Scholar]
  16. Rowley M. J., Gershwin M. E., Mackay I. R. Collagen antibodies in juvenile arthritis and adult rheumatoid arthritis: differences in levels and type-specificity. J Rheumatol. 1988 Feb;15(2):289–294. [PubMed] [Google Scholar]
  17. Rowley M. J., Williamson D. J., Mackay I. R. Evidence for local synthesis of antibodies to denatured collagen in the synovium in rheumatoid arthritis. Arthritis Rheum. 1987 Dec;30(12):1420–1425. doi: 10.1002/art.1780301215. [DOI] [PubMed] [Google Scholar]
  18. Rowley M., Tait B., Mackay I. R., Cunningham T., Phillips B. Collagen antibodies in rheumatoid arthritis. Significance of antibodies to denatured collagen and their association with HLA-DR4. Arthritis Rheum. 1986 Feb;29(2):174–184. doi: 10.1002/art.1780290204. [DOI] [PubMed] [Google Scholar]
  19. STEFFEN C., TIMPL R. Antigenicity of collagen and its application in the serological investigation of rheumatoid arthritis sera. Int Arch Allergy Appl Immunol. 1963;22:333–349. doi: 10.1159/000229376. [DOI] [PubMed] [Google Scholar]
  20. Sasazuki T. Immunogenetic analysis of rheumatoid arthritis. J Rheumatol Suppl. 1983 Nov;10:54–58. [PubMed] [Google Scholar]
  21. Solinger A. M., Bhatnagar R., Stobo J. D. Cellular, molecular, and genetic characteristics of T cell reactivity to collagen in man. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3877–3881. doi: 10.1073/pnas.78.6.3877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Solinger A. M., Stobo J. D. Immune response gene control of collagen reactivity in man: collagen unresponsiveness in HLA-DR4 negative nonresponders is due to the presence of T-dependent suppressive influences. J Immunol. 1982 Nov;129(5):1916–1920. [PubMed] [Google Scholar]
  23. 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]
  24. Sweatman M. C., Markwick J. R., Charles P. J., Jones S. E., Prior J. M., Maini R. N., Turner-Warwick M. E. Histocompatibility antigens in adult obliterative bronchiolitis with or without rheumatoid arthritis. Dis Markers. 1986 Jun;4(1-2):19–26. [PubMed] [Google Scholar]
  25. TERASAKI P. I., MCCLELLAND J. D. MICRODROPLET ASSAY OF HUMAN SERUM CYTOTOXINS. Nature. 1964 Dec 5;204:998–1000. doi: 10.1038/204998b0. [DOI] [PubMed] [Google Scholar]
  26. Trentham D. E., Townes A. S., Kang A. H. Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med. 1977 Sep 1;146(3):857–868. doi: 10.1084/jem.146.3.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Whittingham S., Propert D. N. Gm and Km allotypes, immune response and disease susceptibility. Monogr Allergy. 1986;19:52–70. [PubMed] [Google Scholar]
  28. Wooley P. H., Luthra H. S., Stuart J. M., David C. S. Type II collagen-induced arthritis in mice. I. Major histocompatibility complex (I region) linkage and antibody correlates. J Exp Med. 1981 Sep 1;154(3):688–700. doi: 10.1084/jem.154.3.688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Young A., Jaraquemada D., Awad J., Festenstein H., Corbett M., Hay F. C., Roitt I. M. Association of HLA-DR4/Dw4 and DR2/Dw2 with radiologic changes in a prospective study of patients with rheumatoid arthritis. Preferential relationship with HLA-Dw rather than HLA-DR specificities. Arthritis Rheum. 1984 Jan;27(1):20–25. doi: 10.1002/art.1780270104. [DOI] [PubMed] [Google Scholar]
  30. Young A., Jaraquemada D., Awad J., Festenstein H., Corbett M., Hay F. C., Roitt I. M. Association of HLA-DR4/Dw4 and DR2/Dw2 with radiologic changes in a prospective study of patients with rheumatoid arthritis. Preferential relationship with HLA-Dw rather than HLA-DR specificities. Arthritis Rheum. 1984 Jan;27(1):20–25. doi: 10.1002/art.1780270104. [DOI] [PubMed] [Google Scholar]

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