Skip to main content
NCBI home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1992 Jun;51(6):783–789. doi: 10.1136/ard.51.6.783

Absence of autoantibodies to peptides shared by HLA-B27.5 and Klebsiella pneumoniae nitrogenase in serum samples from HLA-B27 positive patients with ankylosing spondylitis and Reiter's syndrome.

D D de Vries 1, A J Dekker-Saeys 1, E Gyodi 1, U Bohm 1, P Ivanyi 1
PMCID: PMC1004747  PMID: 1616364

Abstract

Some microorganisms which are pathogenic in humans share amino acid sequences with human proteins (molecular mimicry). It has been suggested that molecular mimicry might be a reason for autoimmunity as a result of immunological cross reactivity. A homologous sequence of six amino acids has been found in both Klebsiella pneumoniae nitrogenase and the HLA-B27.5 molecule. In addition, (auto)antibodies to a synthetic peptide that contained the HLA-B27.5/klebsiella mimicking epitope have been detected in serum samples from HLA-B27 positive patients with ankylosing spondylitis and Reiter's syndrome. Confirmation of these data is important, because ankylosing spondylitis and Reiter's syndrome have so far been assumed to be 'seronegative' rheumatic diseases. It was, however, not possible to confirm the presence of autoantibodies against the mimicking peptide in serum samples from patients with ankylosing spondylitis and Reiter's syndrome. Serum samples from 81 patients with ankylosing spondylitis, 38 patients with Reiter's syndrome, and 81 healthy blood donors were tested against the 'mimicking peptide' in an enzyme linked immunosorbent assay (ELISA). Some of the serum samples from patients showed high but non-specific binding to the mimicking peptide. A highly significant correlation between binding to plastic coated with the mimicking peptide, to plastic coated with an irrelevant peptide, and even to non-coated plastic was observed. The nature of the serum component(s) in these patient serum samples (and some control serum samples) responsible for the high non-specific binding to plastic remains unclear. It was also shown that antibodies to the HLA-B27 peptide (containing the mimicking epitope) induced in rabbits do not cross react with the klebsiella peptide and vice versa.

Full text

PDF
783

Selected References

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

  1. Aho K., Ahvonen P., Lassus A., Sievers K., Tilikainen A. HL-A antigen 27 and reactive arthritis. Lancet. 1973 Jul 21;2(7821):157–157. doi: 10.1016/s0140-6736(73)93109-7. [DOI] [PubMed] [Google Scholar]
  2. Archer J. R., Stubbs M. M., Currey H. L., Geczy A. F. Antiserum to Klebsiella K43 BTS 1 specifically lyses lymphocytes of HLA-B27-positive patients with ankylosing spondylitis from a London population. Lancet. 1985 Feb 9;1(8424):344–345. doi: 10.1016/s0140-6736(85)91122-5. [DOI] [PubMed] [Google Scholar]
  3. Archer J. R., Winrow V. R. HLA-B27 and the causes of arthritis: does molecular biology help? Ann Rheum Dis. 1987 Sep;46(9):713–715. doi: 10.1136/ard.46.9.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Breur-Vriesendorp B. S., Dekker-Saeys A. J., Ivanyi P. Distribution of HLA-B27 subtypes in patients with ankylosing spondylitis: the disease is associated with a common determinant of the various B27 molecules. Ann Rheum Dis. 1987 May;46(5):353–356. doi: 10.1136/ard.46.5.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chen J. H., Kono D. H., Yong Z., Park M. S., Oldstone M. M., Yu D. T. A Yersinia pseudotuberculosis protein which cross-reacts with HLA-B27. J Immunol. 1987 Nov 1;139(9):3003–3011. [PubMed] [Google Scholar]
  6. Conger J. D., Pike B. L., Nossal G. J. Analysis of the B lymphocyte repertoire by polyclonal activation. Hindrance by clones yielding antibodies which bind promiscuously to plastic. J Immunol Methods. 1988 Feb 10;106(2):181–189. doi: 10.1016/0022-1759(88)90195-0. [DOI] [PubMed] [Google Scholar]
  7. Ewing C., Ebringer R., Tribbick G., Geysen H. M. Antibody activity in ankylosing spondylitis sera to two sites on HLA B27.1 at the MHC groove region (within sequence 65-85), and to a Klebsiella pneumoniae nitrogenase reductase peptide (within sequence 181-199). J Exp Med. 1990 May 1;171(5):1635–1647. doi: 10.1084/jem.171.5.1635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Geczy A. F., Alexander K., Bashir H. V., Edmonds J. A factor(s) in Klebsiella culture filtrates specifically modifies an HLA-B27 associated cell-surface component. Nature. 1980 Feb 21;283(5749):782–784. doi: 10.1038/283782a0. [DOI] [PubMed] [Google Scholar]
  9. Geczy A. F., van Leeuwen A., van Rood J. J., Ivanyi P., Breur B. S., Cats A. Blind confirmation in Leiden of Geczy factor on the cells of Dutch patients with ankylosing spondylitis. Hum Immunol. 1986 Nov;17(3):239–245. doi: 10.1016/0198-8859(86)90275-2. [DOI] [PubMed] [Google Scholar]
  10. Granfors K., Jalkanen S., Lindberg A. A., Mäki-Ikola O., von Essen R., Lahesmaa-Rantala R., Isomäki H., Saario R., Arnold W. J., Toivanen A. Salmonella lipopolysaccharide in synovial cells from patients with reactive arthritis. Lancet. 1990 Mar 24;335(8691):685–688. doi: 10.1016/0140-6736(90)90804-e. [DOI] [PubMed] [Google Scholar]
  11. Houghten R. A. General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5131–5135. doi: 10.1073/pnas.82.15.5131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Husby G., Tsuchiya N., Schwimmbeck P. L., Keat A., Pahle J. A., Oldstone M. B., Williams R. C., Jr Cross-reactive epitope with Klebsiella pneumoniae nitrogenase in articular tissue of HLA-B27+ patients with ankylosing spondylitis. Arthritis Rheum. 1989 Apr;32(4):437–445. doi: 10.1002/anr.1780320413. [DOI] [PubMed] [Google Scholar]
  13. Håkansson U., Löw B., Eitrem R., Winblad S. HL-A27 and reactive arthritis in an outbreak of salmonellosis. Tissue Antigens. 1975 Nov;6(5):366–367. [PubMed] [Google Scholar]
  14. Kievits F., Wijffels J., Lokhorst W., Boerenkamp W. J., Ivanyi P. HLA expression and function in single and double HLA-B27-transgenic mice. Tissue Antigens. 1989 Jul;34(1):50–63. doi: 10.1111/j.1399-0039.1989.tb01717.x. [DOI] [PubMed] [Google Scholar]
  15. Kono D. H., Ogasawara M., Effros R. B., Park M. S., Waldord R. L., Yu D. T. Ye-1, a monoclonal antibody that cross-reacts with HLA-B27 lymphoblastoid cell lines and an arthritis causing bacteria. Clin Exp Immunol. 1985 Sep;61(3):503–508. [PMC free article] [PubMed] [Google Scholar]
  16. Oldstone M. B. Virus-induced autoimmunity: molecular mimicry as a route to autoimmune disease. J Autoimmun. 1989 Jun;2 (Suppl):187–194. doi: 10.1016/0896-8411(89)90130-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Phillips P. E. The role of infectious agents in the spondylarthropathies. Scand J Rheumatol. 1988;17(6):435–443. doi: 10.3109/03009748809098804. [DOI] [PubMed] [Google Scholar]
  18. Raybourne R. B., Bunning V. K., Williams K. M. Reaction of anti-HLA-B monoclonal antibodies with envelope proteins of Shigella species. Evidence for molecular mimicry in the spondyloarthropathies. J Immunol. 1988 May 15;140(10):3489–3495. [PubMed] [Google Scholar]
  19. Schwimmbeck P. L., Oldstone M. B. Autoimmune pathogenesis for ankylosing spondylitis (AS) and Reiter's syndrome (RS): autoantibodies against an epitope shared by HLA B27 and Klebsiella pneumoniae nitrogenase in sera of HLA B27 patients with AS and RS. Trans Assoc Am Physicians. 1987;100:28–39. [PubMed] [Google Scholar]
  20. Schwimmbeck P. L., Yu D. T., Oldstone M. B. Autoantibodies to HLA B27 in the sera of HLA B27 patients with ankylosing spondylitis and Reiter's syndrome. Molecular mimicry with Klebsiella pneumoniae as potential mechanism of autoimmune disease. J Exp Med. 1987 Jul 1;166(1):173–181. doi: 10.1084/jem.166.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Seager K., Bashir H. V., Geczy A. F., Edmonds J., de Vere-Tyndall A. Evidence for a specific B27-associated cell surface marker on lymphocytes of patients with ankylosing spondylitis. Nature. 1979 Jan 4;277(5691):68–70. doi: 10.1038/277068a0. [DOI] [PubMed] [Google Scholar]
  22. Tsuchiya N., Husby G., Williams R. C., Jr Studies of humoral and cell-mediated immunity to peptides shared by HLA-27.1 and Klebsiella pneumoniae nitrogenase in ankylosing spondylitis. Clin Exp Immunol. 1989 Jun;76(3):354–360. [PMC free article] [PubMed] [Google Scholar]
  23. Welsh J., Avakian H., Cowling P., Ebringer A., Wooley P., Panayi G., Ebringer R. Ankylosing spondylitis, HLA-B27 and Klebsiella. I. Cross-reactivity studies with rabbit antisera. Br J Exp Pathol. 1980 Feb;61(1):85–91. [PMC free article] [PubMed] [Google Scholar]
  24. van Bohemen C. G., Grumet F. C., Zanen H. C. Identification of HLA-B27M1 and -M2 cross-reactive antigens in Klebsiella, Shigella and Yersinia. Immunology. 1984 Aug;52(4):607–610. [PMC free article] [PubMed] [Google Scholar]
  25. van Bohemen C. G., Nabbe A. J., Landheer J. E., Grumet F. C., Mazurkiewicz E. S., Dinant H. J., Lionarons R. J., van Bodegom P. C., Zanen H. C. HLA-B27M1M2 and high immune responsiveness to Shigella flexneri in post-dysenteric arthritis. Immunol Lett. 1986 Aug;13(1-2):71–74. doi: 10.1016/0165-2478(86)90128-8. [DOI] [PubMed] [Google Scholar]

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

RESOURCES