Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Oct;86(4):1193–1203. doi: 10.1172/JCI114825

Autoantibodies to the HLA-B27 sequence cross-react with the hypothetical peptide from the arthritis-associated Shigella plasmid.

N Tsuchiya 1, G Husby 1, R C Williams Jr 1, H Stieglitz 1, P E Lipsky 1, R D Inman 1
PMCID: PMC296849  PMID: 2212008

Abstract

We previously reported elevated serum antibody levels to a peptide representing the HLA-B27 polymorphic region (B27 peptide) in HLA-B27(+) ankylosing spondylitis (AS) patients. A plasmid (pHS-2) isolated from arthritogenic Shigella flexneri strains had been shown to encode an amino acid sequence homologous to HLA-B27. Rabbit antibody to this sequence (pHS-2 peptide) strongly cross-reacted with B27 peptide and, to a much lesser extent, with Klebsiella nitrogenase peptide. Serum antibody levels to pHS-2 peptide were studied in 160 spondylarthropathy patients. 12 of 115 (10.4%) AS patients, 2 of 45 (4.4%) patients with Reiter's syndrome or reactive arthritis as well as 6 of 147 (4.1%) normal controls were shown to have elevated anti-pHS-2 peptide antibodies. Antibody levels to B27 and pHS-2 peptides were significantly correlated in 134 HLA-B27(+) patients (r = 0.333, P less than 0.001). 13 of 15 affinity-purified anti-B27 peptide antibodies from patients strongly cross-reacted with pHS-2 peptide, whereas only 3 weakly cross-reacted to nitrogenase peptide. Leucine appeared to be a critical residue for this cross-reaction. AS patients' anti-B27 peptide antibodies reacted with HLA-B27 transfected L cells. These results may suggest that pHS-2 peptide more efficiently "mimics" B27 peptide than does nitrogenase peptide. Involvement of pHS-2 in pathogenesis of spondylarthropathy through molecular mimicry mechanisms requires further study.

Full text

PDF
1193

Selected References

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

  1. Ahrons S. HL-A antibodies: influence on the human foetus. Tissue Antigens. 1971;1(3):129–136. [PubMed] [Google Scholar]
  2. Aparicio P., Rojo S., Jaraquemada D., López de Castro J. A. Fine specificity of HLA-B27 cellular allorecognition. HLA-B27f is a functional variant distinguishable by cytolytic T cell clones. J Immunol. 1987 Aug 1;139(3):837–841. [PubMed] [Google Scholar]
  3. Avakian H., Welsh J., Ebringer A., Entwistle C. C. Ankylosing spondylitis, HLA-B27 and Klebsiella. II. Cross-reactivity studies with human tissue typing sera. Br J Exp Pathol. 1980 Feb;61(1):92–96. [PMC free article] [PubMed] [Google Scholar]
  4. Baumgarten H. A cell ELISA for the quantitation of leukocyte antigens. Requirements for calibration. J Immunol Methods. 1986 Nov 20;94(1-2):91–98. doi: 10.1016/0022-1759(86)90219-x. [DOI] [PubMed] [Google Scholar]
  5. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987 Oct 8;329(6139):506–512. doi: 10.1038/329506a0. [DOI] [PubMed] [Google Scholar]
  6. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987 Oct 8;329(6139):512–518. doi: 10.1038/329512a0. [DOI] [PubMed] [Google Scholar]
  7. Cavender D., Ziff M. Anti-HLA-B27 antibodies in sera from patients with gram-negative bacterial infections. Arthritis Rheum. 1986 Mar;29(3):352–357. doi: 10.1002/art.1780290307. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Dyrberg T., Oldstone M. B. Peptides as probes to study molecular mimicry and virus-induced autoimmunity. Curr Top Microbiol Immunol. 1986;130:25–37. doi: 10.1007/978-3-642-71440-5_3. [DOI] [PubMed] [Google Scholar]
  11. Geczy A. F., Alexander K., Bashir H. V., Edmonds J. P., Upfold L., Sullivan J. HLA-B27, Klebsiella and ankylosing spondylitis: biological and chemical studies. Immunol Rev. 1983;70:23–50. doi: 10.1111/j.1600-065x.1983.tb00708.x. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Geppert T. D., Wacholtz M. C., Patel S. S., Lightfoot E., Lipsky P. E. Activation of human T cell clones and Jurkat cells by cross-linking class I MHC molecules. J Immunol. 1989 Jun 1;142(11):3763–3772. [PubMed] [Google Scholar]
  14. Getzoff E. D., Tainer J. A., Lerner R. A., Geysen H. M. The chemistry and mechanism of antibody binding to protein antigens. Adv Immunol. 1988;43:1–98. doi: 10.1016/s0065-2776(08)60363-6. [DOI] [PubMed] [Google Scholar]
  15. Granfors K., Jalkanen S., von Essen R., Lahesmaa-Rantala R., Isomäki O., Pekkola-Heino K., Merilahti-Palo R., Saario R., Isomäki H., Toivanen A. Yersinia antigens in synovial-fluid cells from patients with reactive arthritis. N Engl J Med. 1989 Jan 26;320(4):216–221. doi: 10.1056/NEJM198901263200404. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Inman R. D., Chiu B., Johnston M. E., Falk J. Molecular mimicry in Reiter's syndrome: cytotoxicity and ELISA studies of HLA-microbial relationships. Immunology. 1986 Jul;58(3):501–506. [PMC free article] [PubMed] [Google Scholar]
  18. Inman R. D., Chiu B., Johnston M. E., Vas S., Falk J. HLA class I-related impairment in IL-2 production and lymphocyte response to microbial antigens in reactive arthritis. J Immunol. 1989 Jun 15;142(12):4256–4260. [PubMed] [Google Scholar]
  19. Ishikawa H., Ohno O., Yamasaki K., Ikuta S., Hirohata K. Arthritis presumably caused by Chlamydia in Reiter syndrome. Case report with electron microscopic studies. J Bone Joint Surg Am. 1986 Jun;68(5):777–779. [PubMed] [Google Scholar]
  20. Keat A. Reiter's syndrome and reactive arthritis in perspective. N Engl J Med. 1983 Dec 29;309(26):1606–1615. doi: 10.1056/NEJM198312293092604. [DOI] [PubMed] [Google Scholar]
  21. Keat A., Thomas B., Dixey J., Osborn M., Sonnex C., Taylor-Robinson D. Chlamydia trachomatis and reactive arthritis: the missing link. Lancet. 1987 Jan 10;1(8524):72–74. doi: 10.1016/s0140-6736(87)91910-6. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Merrifield R. B. Solid-phase peptide synthesis. Adv Enzymol Relat Areas Mol Biol. 1969;32:221–296. doi: 10.1002/9780470122778.ch6. [DOI] [PubMed] [Google Scholar]
  24. Okudaira K., Searles R. P., Ceuppens J. L., Goodwin J. S., Williams R. C., Jr Anti-Ia reactivity in sera from patients with systemic lupus erythematosus. J Clin Invest. 1982 Jan;69(1):17–24. doi: 10.1172/JCI110428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Portnoy D. A., Wolf-Watz H., Bolin I., Beeder A. B., Falkow S. Characterization of common virulence plasmids in Yersinia species and their role in the expression of outer membrane proteins. Infect Immun. 1984 Jan;43(1):108–114. doi: 10.1128/iai.43.1.108-114.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Rojo S., López de Castro J. A., Aparicio P., Van Seventer G., Bragado R. HLA-B27 antigenicity: antibodies against the chemically synthesized 63-84 peptide from HLA-B27.1 display alloantigenic specificity and discriminate among HLA-B27 subtypes. J Immunol. 1986 Aug 1;137(3):904–910. [PubMed] [Google Scholar]
  28. Schumacher H. R., Jr, Magge S., Cherian P. V., Sleckman J., Rothfuss S., Clayburne G., Sieck M. Light and electron microscopic studies on the synovial membrane in Reiter's syndrome. Immunocytochemical identification of chlamydial antigen in patients with early disease. Arthritis Rheum. 1988 Aug;31(8):937–946. doi: 10.1002/art.1780310801. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. Stieglitz H., Fosmire S., Lipsky P. E. Bacterial epitopes involved in the induction of reactive arthritis. Am J Med. 1988 Dec 23;85(6A):56–58. doi: 10.1016/0002-9343(88)90387-7. [DOI] [PubMed] [Google Scholar]
  32. Stieglitz H., Fosmire S., Lipsky P. Identification of a 2-Md plasmid from Shigella flexneri associated with reactive arthritis. Arthritis Rheum. 1989 Aug;32(8):937–946. doi: 10.1002/anr.1780320802. [DOI] [PubMed] [Google Scholar]
  33. Sundaresan V., Ausubel F. M. Nucleotide sequence of the gene coding for the nitrogenase iron protein from Klebsiella pneumoniae. J Biol Chem. 1981 Mar 25;256(6):2808–2812. [PubMed] [Google Scholar]
  34. Taurog J. D., el-Zaatari F. A. In vitro mutagenesis of HLA-B27. Substitution of an unpaired cysteine residue in the alpha 1 domain causes loss of antibody-defined epitopes. J Clin Invest. 1988 Sep;82(3):987–992. doi: 10.1172/JCI113708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Trull A., Ebringer A., Panayi G., Ebringer R., James D. C. HLA-B27 and the immune response to enterobacterial antigens in ankylosing spondylitis. Clin Exp Immunol. 1984 Jan;55(1):74–80. [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. 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]
  38. 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]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES