Skip to main content

Advertisement

Log in

Antibacterial and antipeptide antibodies in Japanese and Finnish patients with rheumatoid arthritis

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

It has been suggested that Proteus infection may be involved in the pathogenesis of rheumatoid arthritis (RA). Bacterial and peptide immune responses in patients with RA and other control subjects were investigated in two geographically different populations. Serum samples from Finnish patients with early (n=72) and advanced (n=27) RA and 30 Finnish healthy controls, as well as from Japanese RA patients from two different locations: Tokyo (n=30) and Otsu (n=30), 18 patients with systemic lupus erythematosus (SLE) and 23 Japanese healthy controls were all screened for the total, and class-specific (IgG, IgA and IgM) antibodies against Proteus mirabilis, Escherichia coli and Serratia marcescens by indirect immunofluorescence assay. These samples were also tested for the determination of levels of isotypic antibodies against the shared epitope involving 16-mer synthetic peptides containing the EQRRAA or ESSRAL sequences and compared to scrambled control peptide by using an enzyme-labeled immunosorbent assay method. Significantly elevated levels of IgG and IgM antibodies to P. mirabilis and antibodies against both EQRRAA and ESSRAL peptides were detected in sera of Finnish patients with early and advanced RA, and in Japanese patients from Otsu or Tokyo compared to their corresponding control groups. In contrast, no difference either in the total or in any of the isotypic antibodies were observed between these groups when serum samples were screened against each of E. coli and S. marcescens or against the control peptide. Furthermore, there was a significant correlation between the antibody levels against Proteus bacteria only and both EQRRAA and ESRRAL peptides. Our findings support the possibility for specific involvement of P. mirabilis in the etiopathogenesis of RA even in early cases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

ELISA:

Enzyme linked immunosorbent assay

IIF:

Immunofluorescence

RA:

Rheumatoid arthritis

SLE:

Systemic lupus erythematosus

References

  1. Carty SM, Snowden N, Silman AJ (2003) Should infection still be considered as the most likely triggering factor for rheumatoid arthritis? J Rheumatol 30:425–429

    PubMed  Google Scholar 

  2. Stastny P (1976) Mixed lymphocyte cultures in rheumatoid arthritis. J Clin Invest 57:1148–1157

    CAS  PubMed  Google Scholar 

  3. Nakai Y, Wakisaka A, Aizawa M, Itakura K, Nakai H, Ohashi A (1981) HLA and rheumatoid arthritis in Japanese. Arthritis Rheum 24:722–725

    CAS  PubMed  Google Scholar 

  4. Ohta N, Nishimura YK, Tanimoto K et al. (1982) Association between HLA and Japanese patients with rheumatoid arthritis. Hum Immunol 5:123–132

    Article  CAS  PubMed  Google Scholar 

  5. Gorodezky C, Lavalle C, Castro-Escobar LE, Miranda-Limon JM, Escobar-Gutierrez A (1981) HLA antigens in Mexican patients with adult rheumatoid arthritis. Arthritis Rheum 24:976–977

    CAS  PubMed  Google Scholar 

  6. Alarcon GS, Koopman WJ, Acton RT, Barger BO (1983) DR antigen distribution in blacks with rheumatoid arthritis. J Rheumatol 10:579–583

    CAS  PubMed  Google Scholar 

  7. Woodrow JC, Nichol FE, Zaphiropoulos G (1981) DR antigens and rheumatoid arthritis: a study of two populations. Br Med J 283:1287–1288

    CAS  Google Scholar 

  8. Schiff B, Mizrachi Y, Orgad S, Yaron M, Gazit E (1982) Association of HLA-Aw31 and HLA-DR1 with adult rheumatoid arthritis. Ann Rheum Dis 41:403–404

    CAS  PubMed  Google Scholar 

  9. Willkens RF, Hansen JA, Malmgren JA, Nisperos B, Mickelson EM, Watson MA (1982) HLA antigens in Yakima Indians with rheumatoid arthritis. Lack of association with HLA-Dw4 and HLA-DR4. Arthritis Rheum 25:1435–1439

    CAS  PubMed  Google Scholar 

  10. Watanabe Y, Tokunaga K, Matsuki K et al. (1989) Putative amino acid sequence of HLA-DRß chain contributing to rheumatoid arthritis susceptibility. J Exp Med 169:2263–2268

    CAS  PubMed  Google Scholar 

  11. Wallin J, Hillert J, Olerup O, Carlsson B, Strom H (1991) Association of rheumatoid arthritis with a dominant DR1/Dw4/Dw14 sequence motif, but not with T cell receptor beta chain gene alleles or haplotypes. Arthritis Rheum 34:1416–1424

    CAS  PubMed  Google Scholar 

  12. Gregersen PK, Silver J, Winchester RJ (1987) The shared epitope hypothesis: An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 30:1205–1213

    CAS  PubMed  Google Scholar 

  13. Tuokko J, Nejentsev S, Luukkainen R, Toivanen A, Ilonen J (2001) HLA haplotype analysis in Finnish patients with rheumatoid arthritis. Arthritis Rheum 44:315–322

    Article  CAS  PubMed  Google Scholar 

  14. De Vries N, Tijssen H, Jarvinen P, Aho K, van de Putte LB (1997) HLA-DRB1 in eight Finnish monozygotic twin pairs concordant for rheumatoid arthritis. Tissue Antigens 49:277–279

    PubMed  Google Scholar 

  15. Takeuchi F, Nakano K, Matsuta K et al. (1996) Positive and negative association of HLA-DR genotypes with Japanese rheumatoid arthritis. Clin Exp Rheumatol 14:17–22

    CAS  PubMed  Google Scholar 

  16. Albani S, Tuckwell JE, Esparza L, Carson DA, Roudier J (1992) The susceptibility sequence to rheumatoid arthritis is a cross-reactive B cell epitope shared by the Escherichia coli heat shock protein dnaJ and the histocompatibility leukocyte antigen DRB10401 molecule. J Clin Invest 89:327–331

    CAS  PubMed  Google Scholar 

  17. Uphoff TS, Welch RA (1990) Nucleotide sequencing of the Proteus mirabilis calcium independent hemolysin genes (hpmA and hpmB) reveals sequence similarity with the Serratia marcescens hemolysin genes (shlA and shlB). J Bacteriol 172:1206–1216

    CAS  PubMed  Google Scholar 

  18. Poole K, Schiebel E, and Braun V (1988) Molecular characterization of the hemolysin determinant of Serratia marcescens. J Bacteriol 170:3177–3188

    CAS  PubMed  Google Scholar 

  19. Ebringer A, Cunningham P, Ahmadi K, Wrigglesworth J, Hosseini R, Wilson C (1992) Sequence similarity between HLA-DR1 and DR4 subtypes associated with rheumatoid arthritis and Proteus/Serratia membrane haemolysins. Ann Rheum Dis 51:1245–1246

    CAS  PubMed  Google Scholar 

  20. Takeuchi F, Kosuge E, Matsuta K et al. (1990) Antibody to a specific HLA-DR beta 1 sequence in Japanese patients with rheumatoid arthritis. Arthritis Rheum 33:1867–1868

    CAS  PubMed  Google Scholar 

  21. Wilson C, Ebringer A, Ahmadi K et al. (1995) Shared amino acid sequences between major histocompatibility complex class II glycoproteins, type XI collagen and Proteus mirabilis in rheumatoid arthritis. Ann Rheum Dis 54:216–220

    CAS  PubMed  Google Scholar 

  22. Aho K, Koskenvuo M, Tuominen J, Kaprio J (1986). Occurrence of rheumatoid arthritis in a nationwide series of twins. J Rheumatol 13:899–902

    CAS  PubMed  Google Scholar 

  23. Silman AJ, MacGregor AJ, Thomson W et al. (1993) Twin concordance rates for rheumatoid arthritis: results from a nation-wide study. Br J Rheumatol 32:903–907

    CAS  PubMed  Google Scholar 

  24. Ebringer A, Ptaszynska T, Corbett M et al. (1985) Antibodies to Proteus in rheumatoid arthritis. Lancet ii: 305–307

    Article  Google Scholar 

  25. Rogers P, Hassan J, Bresnihan B, Feighery C, Whelan A (1988) Antibodies to Proteus in rheumatoid arthritis. Br J Rheumatol 27 (Suppl 2): 90–94

    PubMed  Google Scholar 

  26. Deighton CM, Gray JW, Bint AJ, Walker DJ (1992) Anti-Proteus antibodies in rheumatoid arthritis same-sexed sibships. Br J Rheumatol 31:241–245

    CAS  PubMed  Google Scholar 

  27. Senior BW, McBride PD, Morley KD, Kerr MA (1995) The detection of raised level of IgM to Proteus mirabilis in sera from patients with rheumatoid arthritis. J Med Microbiol 43:176–184

    CAS  PubMed  Google Scholar 

  28. Rashid T, Darlington G, Kjeldsen-Kragh J, Forre O, Collado A, Ebringer A (1999) Proteus IgG antibodies and C-reactive protein in English, Norwegian and Spanish patients with rheumatoid arthritis. Clin Rheumatol 18:190–195

    Article  CAS  PubMed  Google Scholar 

  29. Ebringer A, Rashid T, Wilson C (2003) Rheumatoid arthritis: proposal for the use of anti-microbial therapy in early cases. Scand J Rheumatol 32:2–11

    PubMed  Google Scholar 

  30. Arnett FC, Edworthy SM, Bloch DA et al. (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    CAS  PubMed  Google Scholar 

  31. Merrifield RB. Solid-phase peptide synthesis (1969) Adv Enzymol Relat Areas Mol Biol 32:221–296

    CAS  PubMed  Google Scholar 

  32. Ebringer A, Cox NL, Abuljadayel I et al. (1988) Klebsiella antibodies in ankylosing spondylitis and Proteus antibodies in rheumatoid arthritis. Br J Rheumatol 27 (Suppl 2): 72–85

    Google Scholar 

  33. Deighton CM, Gray J, Bint AJ, Walker DJ (1992) Specificity of the Proteus antibody response in rheumatoid arthritis. Ann Rheum Dis 51:1206–1207

    CAS  PubMed  Google Scholar 

  34. Kjeldsen-Kragh J, Rashid T, Dybward A et al. (1995) Decrease in anti-Proteus mirabilis but not anti-Escherichia coli antibody levels in rheumatoid arthritis patients treated with fasting and a one year vegetarian diet. Ann Rheum Dis 54:221–224

    CAS  PubMed  Google Scholar 

  35. Fielder M, Tiwana H, Youinou P et al. (1995) The specificity of the anti-Proteus antibody response in tissue-typed rheumatoid arthritis (RA) patients from Brest. Rheumatol Int 15:79–82

    CAS  PubMed  Google Scholar 

  36. Subair H, Tiwana H, Fielder M et al. (1995) Elevation in anti-Proteus antibodies in patients with rheumatoid arthritis from Bermuda and England. J Rheumatol 22:1825–1828

    CAS  PubMed  Google Scholar 

  37. Tiwana H, Wilson C, Cunningham P, Binder A and Ebringer A (1996) Antibodies to four gram-negative bacteria in rheumatoid arthritis which share sequences with the rheumatoid arthritis susceptibility motif. Br J Rheumatol 35:592–594

    CAS  PubMed  Google Scholar 

  38. Tani Y, Tiwana H, Hukuda S et al. (1997) Antibodies to Klebsiella, Proteus, and HLA-B27 peptides in Japanese patients with ankylosing spondylitis and rheumatoid arthritis. J Rheumatol 24:109–14

    CAS  PubMed  Google Scholar 

  39. Murphy EA, Mowat L and Sturrock RD (1991) Antibodies to Proteus in rheumatoid arthritis. Br J Rheumatol 30:390

    CAS  Google Scholar 

  40. Dybwad A, Forre O, and Sioud M (1996) Increased serum and synovial antibodies to immunoselected peptides in patients with rheumatoid arthritis. Ann Rheum Dis 55:437–441

    CAS  PubMed  Google Scholar 

  41. Wilson C, Rashid T, Tiwana H et al. (2003) Cytotoxicity responses to peptide antigens in rheumatoid arthritis and ankylosing spondylitis. J Rheumatol 30:972–978

    CAS  PubMed  Google Scholar 

  42. Swihart KG, Welch RA (1990) The HpmA hemolysin is more common than HlyA among Proteus isolates. Infect Immun 58:1853–1860

    CAS  PubMed  Google Scholar 

Download references

Aknowledgements

We thank the Trustees of the Middlesex Hospital and the Arthritis Research Campaign for their support (Grant E0514).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. Ebringer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rashid, T., Leirisalo-Repo, M., Tani, Y. et al. Antibacterial and antipeptide antibodies in Japanese and Finnish patients with rheumatoid arthritis. Clin Rheumatol 23, 134–141 (2004). https://doi.org/10.1007/s10067-003-0847-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-003-0847-6

Keywords

Navigation