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. 2002 Nov;61(11):1012–1016. doi: 10.1136/ard.61.11.1012

Infectious background of patients with a history of acute anterior uveitis

M Huhtinen 1, K Laasila 1, K Granfors 1, M Puolakkainen 1, I Seppala 1, L Laasonen 1, H Repo 1, A Karma 1, M Leirisalo-Repo 1
PMCID: PMC1753942  PMID: 12379526

Abstract

Objective: To study the infectious backround of patients with a history of acute anterior uveitis (AAU) and healthy control subjects.

Methods: Sixty four patients with previous AAU and 64 sex and age matched controls were studied. Serum antibodies to Salmonellae, Yersiniae, Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, Campylobacter jejuni, and Borrelia burgdorferi were measured using enzyme linked immunosorbent assay (ELISA), and antibodies to Chlamydia trachomatis and Chlamydia pneumoniae by microimmunofluorescence test. Peripheral blood mononuclear cells (PBMCs), separated by density gradient centrifugation, were studied for Salmonella and Yersinia antigens by means of an immunofluorescence test, and for C pneumoniae DNA with a polymerase chain reaction (PCR).

Results: Neither prevalence nor levels of single microbial antibodies studied differed between the patients and control subjects, or between subgroups of patients created on the basis of clinical characteristics. In logistic regression analysis, the high number of recurrences (>10) of AAU was independently related to the presence of single or multiple bacterial antibodies (p=0.04). None of the PBMC samples of the patients were positive for Yersinia or Salmonella antigens. C pneumoniae PCR was positive in a patient who was negative for C pneumoniae antibodies.

Conclusion: Although neither the prevalence nor the levels of single microbial antibodies studied differed between the patients and the controls, current data suggest that the presence of single or multiple antibodies in patients with many recurrences of AAU compared with patients with none or few recurrences may be a sign of repeated infections, antigen persistence, or raised innate immune responsiveness.

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Selected References

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  1. Baggia S., Lyons J. L., Angell E., Barkhuizen A., Han Y. B., Planck S. R., Taurog J. D., Rosenbaum J. T. A novel model of bacterially-induced acute anterior uveitis in rats and the lack of effect from HLA-B27 expression. J Investig Med. 1997 Jun;45(5):295–301. [PubMed] [Google Scholar]
  2. Bas S., Griffais R., Kvien T. K., Glennås A., Melby K., Vischer T. L. Amplification of plasmid and chromosome Chlamydia DNA in synovial fluid of patients with reactive arthritis and undifferentiated seronegative oligoarthropathies. Arthritis Rheum. 1995 Jul;38(7):1005–1013. doi: 10.1002/art.1780380718. [DOI] [PubMed] [Google Scholar]
  3. Boman J., Söderberg S., Forsberg J., Birgander L. S., Allard A., Persson K., Jidell E., Kumlin U., Juto P., Waldenström A. High prevalence of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in patients with cardiovascular disease and in middle-aged blood donors. J Infect Dis. 1998 Jul;178(1):274–277. doi: 10.1086/517452. [DOI] [PubMed] [Google Scholar]
  4. Braun J., Laitko S., Treharne J., Eggens U., Wu P., Distler A., Sieper J. Chlamydia pneumoniae--a new causative agent of reactive arthritis and undifferentiated oligoarthritis. Ann Rheum Dis. 1994 Feb;53(2):100–105. doi: 10.1136/ard.53.2.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brewerton D. A., Caffrey M., Nicholls A., Walters D., James D. C. Acute anterior uveitis and HL-A 27. Lancet. 1973 Nov 3;302(7836):994–996. doi: 10.1016/s0140-6736(73)91090-8. [DOI] [PubMed] [Google Scholar]
  6. Dougados M., van der Linden S., Juhlin R., Huitfeldt B., Amor B., Calin A., Cats A., Dijkmans B., Olivieri I., Pasero G. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum. 1991 Oct;34(10):1218–1227. doi: 10.1002/art.1780341003. [DOI] [PubMed] [Google Scholar]
  7. Ebringer R., Cawdell D., Ebringer A. Klebsiella pneumoniae and acute anterior uveitis in ankylosing spondylitis. Br Med J. 1979 Feb 10;1(6160):383–383. doi: 10.1136/bmj.1.6160.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Granfors K., Jalkanen S., Toivanen P., Koski J., Lindberg A. A. Bacterial lipopolysaccharide in synovial fluid cells in Shigella triggered reactive arthritis. J Rheumatol. 1992 Mar;19(3):500–500. [PubMed] [Google Scholar]
  11. 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]
  12. Granfors K., Lahesmaa-Rantala R., Ståhlberg T. H., Toivanen A. Comparison of bacteria with and without plasmid-encoded proteins as antigens for measurement of immunoglobulin M, G, and A antibodies to Yersinia enterocolitica by enzyme-linked immunosorbent assay. J Clin Microbiol. 1989 Mar;27(3):583–585. doi: 10.1128/jcm.27.3.583-585.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Granfors K., Merilahti-Palo R., Luukkainen R., Möttönen T., Lahesmaa R., Probst P., Märker-Hermann E., Toivanen P. Persistence of Yersinia antigens in peripheral blood cells from patients with Yersinia enterocolitica O:3 infection with or without reactive arthritis. Arthritis Rheum. 1998 May;41(5):855–862. doi: 10.1002/1529-0131(199805)41:5<855::AID-ART12>3.0.CO;2-J. [DOI] [PubMed] [Google Scholar]
  14. Granfors K., Viljanen M., Tiilikainen A., Toivanen A. Persistence of IgM, IgG, and IgA antibodies to Yersinia in yersinia arthritis. J Infect Dis. 1980 Apr;141(4):424–429. doi: 10.1093/infdis/141.4.424. [DOI] [PubMed] [Google Scholar]
  15. Hammer M., Nettelnbreker E., Hopf S., Schmitz E., Pörschke K., Zeidler H. Chlamydial rRNA in the joints of patients with Chlamydia-induced arthritis and undifferentiated arthritis. Clin Exp Rheumatol. 1992 Jan-Feb;10(1):63–66. [PubMed] [Google Scholar]
  16. Hoogkamp-Korstanje J. A., de Koning J., Heesemann J. Persistence of Yersinia enterocolitica in man. Infection. 1988 Mar-Apr;16(2):81–85. doi: 10.1007/BF01644307. [DOI] [PubMed] [Google Scholar]
  17. Huhtinen M., Puolakkainen M., Laasila K., Sarvas M., Karma A., Leirisalo-Repo M. Chlamydial antibodies in patients with previous acute anterior uveitis. Invest Ophthalmol Vis Sci. 2001 Jul;42(8):1816–1819. [PubMed] [Google Scholar]
  18. Huhtinen M., Repo H., Laasila K., Jansson S-E, Kautiainen H., Karma A., Leirisalo-Repo M. Systemic inflammation and innate immune response in patients with previous anterior uveitis. Br J Ophthalmol. 2002 Apr;86(4):412–417. doi: 10.1136/bjo.86.4.412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Huppertz H. I., Heesemann J. The influence of HLA B27 and interferon-gamma on the invasion and persistence of yersinia in primary human fibroblasts. Med Microbiol Immunol. 1996 Nov;185(3):163–170. doi: 10.1007/s004300050027. [DOI] [PubMed] [Google Scholar]
  20. Höhler T., Hug R., Schneider P. M., Krummenauer F., Gripenberg-Lerche C., Granfors K., Märker-Hermann E. Ankylosing spondylitis in monozygotic twins: studies on immunological parameters. Ann Rheum Dis. 1999 Jul;58(7):435–440. doi: 10.1136/ard.58.7.435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ikawa T., Ikeda M., Yamaguchi A., Tsai W. C., Tamura N., Seta N., Trucksess M., Raybourne R. B., Yu D. T. Expression of arthritis-causing HLA-B27 on Hela cells promotes induction of c-fos in response to in vitro invasion by Salmonella typhimurium. J Clin Invest. 1998 Jan 1;101(1):263–272. doi: 10.1172/JCI471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Isomäki O., Vuento R., Granfors K. Serological diagnosis of salmonella infections by enzyme immunoassay. Lancet. 1989 Jun 24;1(8652):1411–1414. doi: 10.1016/s0140-6736(89)90124-4. [DOI] [PubMed] [Google Scholar]
  23. Kapasi K., Inman R. D. HLA-B27 expression modulates gram-negative bacterial invasion into transfected L cells. J Immunol. 1992 Jun 1;148(11):3554–3559. [PubMed] [Google Scholar]
  24. Karma A., Seppälä I., Mikkilä H., Kaakkola S., Viljanen M., Tarkkanen A. Diagnosis and clinical characteristics of ocular Lyme borreliosis. Am J Ophthalmol. 1995 Feb;119(2):127–135. doi: 10.1016/s0002-9394(14)73864-4. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Krutzik S. R., Sieling P. A., Modlin R. L. The role of Toll-like receptors in host defense against microbial infection. Curr Opin Immunol. 2001 Feb;13(1):104–108. doi: 10.1016/s0952-7915(00)00189-8. [DOI] [PubMed] [Google Scholar]
  27. Laitio P., Virtala M., Salmi M., Pelliniemi L. J., Yu D. T., Granfors K. HLA-B27 modulates intracellular survival of Salmonella enteritidis in human monocytic cells. Eur J Immunol. 1997 Jun;27(6):1331–1338. doi: 10.1002/eji.1830270606. [DOI] [PubMed] [Google Scholar]
  28. Leirisalo M., Skylv G., Kousa M., Voipio-Pulkki L. M., Suoranta H., Nissilä M., Hvidman L., Nielsen E. D., Svejgaard A., Tilikainen A. Followup study on patients with Reiter's disease and reactive arthritis, with special reference to HLA-B27. Arthritis Rheum. 1982 Mar;25(3):249–259. doi: 10.1002/art.1780250302. [DOI] [PubMed] [Google Scholar]
  29. Mattila L., Granfors K., Toivanen A. Acute anterior uveitis after yersinia infection. Br J Ophthalmol. 1982 Mar;66(3):209–212. doi: 10.1136/bjo.66.3.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mattila L., Salminen L., Terho P. Chlamydial immunofluorescence serology in anterior uveitis. Br J Ophthalmol. 1982 Oct;66(10):654–657. doi: 10.1136/bjo.66.10.654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Merilahti-Palo R., Söderström K. O., Lahesmaa-Rantala R., Granfors K., Toivanen A. Bacterial antigens in synovial biopsy specimens in yersinia triggered reactive arthritis. Ann Rheum Dis. 1991 Feb;50(2):87–90. doi: 10.1136/ard.50.2.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mäki-Ikola O., Lehtinen K., Toivanen P., Granfors K. Antibodies to Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis in the sera of ankylosing spondylitis patients with/without iritis and enthesitis. Br J Rheumatol. 1995 May;34(5):418–420. doi: 10.1093/rheumatology/34.5.418. [DOI] [PubMed] [Google Scholar]
  33. Mäki-Ikola O., Leirisalo-Repo M., Kantele A., Toivanen P., Granfors K. Salmonella-specific antibodies in reactive arthritis. J Infect Dis. 1991 Dec;164(6):1141–1148. doi: 10.1093/infdis/164.6.1141. [DOI] [PubMed] [Google Scholar]
  34. Mäki-Ikola O., Penttinen M., Von Essen R., Gripenberg-Lerche C., Isomäki H., Granfors K. IgM, IgG and IgA class enterobacterial antibodies in serum and synovial fluid in patients with ankylosing spondylitis and rheumatoid arthritis. Br J Rheumatol. 1997 Oct;36(10):1051–1053. doi: 10.1093/rheumatology/36.10.1051. [DOI] [PubMed] [Google Scholar]
  35. Nickerson C. L., Luthra H. S., Savarirayan S., David C. S. Susceptibility of HLA-B27 transgenic mice to Yersinia enterocolitica infection. Hum Immunol. 1990 Aug;28(4):382–396. doi: 10.1016/0198-8859(90)90033-l. [DOI] [PubMed] [Google Scholar]
  36. Nikkari S., Rantakokko K., Ekman P., Möttönen T., Leirisalo-Repo M., Virtala M., Lehtonen L., Jalava J., Kotilainen P., Granfors K. Salmonella-triggered reactive arthritis: use of polymerase chain reaction, immunocytochemical staining, and gas chromatography-mass spectrometry in the detection of bacterial components from synovial fluid. Arthritis Rheum. 1999 Jan;42(1):84–89. doi: 10.1002/1529-0131(199901)42:1<84::AID-ANR11>3.0.CO;2-C. [DOI] [PubMed] [Google Scholar]
  37. Nissilä M., Lahesmaa R., Leirisalo-Repo M., Lehtinen K., Toivanen P., Granfors K. Antibodies to Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis in ankylosing spondylitis: effect of sulfasalazine treatment. J Rheumatol. 1994 Nov;21(11):2082–2087. [PubMed] [Google Scholar]
  38. Pekkola-Heino K., Viljanen M. K., Ståhlberg T. H., Granfors K., Toivanen A. Monoclonal antibodies reacting selectively with core and O-polysaccharide of Yersinia enterocolitica O:3 lipopolysaccharide. Acta Pathol Microbiol Immunol Scand C. 1987 Feb;95(1):27–34. doi: 10.1111/j.1699-0463.1987.tb00005.x. [DOI] [PubMed] [Google Scholar]
  39. Probst P., Hermann E., Meyer zum Büschenfelde K. H., Fleischer B. Multiclonal synovial T cell response to Yersinia enterocolitica in reactive arthritis: the Yersinia 61-kDa heat-shock protein is not the major target antigen. J Infect Dis. 1993 Feb;167(2):385–391. doi: 10.1093/infdis/167.2.385. [DOI] [PubMed] [Google Scholar]
  40. Rautelin H., Kosunen T. U. An acid extract as a common antigen in Campylobacter coli and Campylobacter jejuni strains. J Clin Microbiol. 1983 Apr;17(4):700–701. doi: 10.1128/jcm.17.4.700-701.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rose N. R. The role of infection in the pathogenesis of autoimmune disease. Semin Immunol. 1998 Feb;10(1):5–13. doi: 10.1006/smim.1997.0100. [DOI] [PubMed] [Google Scholar]
  42. Saari K. M., Vilppula A., Lassus A., Leirisalo M., Saari R. Ocular inflammation in Reiter's disease after Salmonella enteritis. Am J Ophthalmol. 1980 Jul;90(1):63–68. doi: 10.1016/s0002-9394(14)75077-9. [DOI] [PubMed] [Google Scholar]
  43. Schumacher H. R., Jr, Arayssi T., Crane M., Lee J., Gerard H., Hudson A. P., Klippel J. Chlamydia trachomatis nucleic acids can be found in the synovium of some asymptomatic subjects. Arthritis Rheum. 1999 Jun;42(6):1281–1284. doi: 10.1002/1529-0131(199906)42:6<1281::AID-ANR27>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
  44. 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]
  45. Seppälä I. J., Kroneld R., Schauman K., Forsen K. O., Lassenius R. Diagnosis of Lyme borreliosis: non-specific serological reactions with Borrelia burgdorferi sonicate antigen caused by IgG2 antibodies. J Med Microbiol. 1994 Apr;40(4):293–302. doi: 10.1099/00222615-40-4-293. [DOI] [PubMed] [Google Scholar]
  46. Shodjai-Moradi F., Ebringer A., Abuljadayel I. IgA antibody response to klebsiella in ankylosing spondylitis measured by immunoblotting. Ann Rheum Dis. 1992 Feb;51(2):233–237. doi: 10.1136/ard.51.2.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sprenkels S. H., Uksila J., Vainionpä R., Toivanen P., Feltkamp T. E. IgA antibodies in HLA-B27 associated acute anterior uveitis and ankylosing spondylitis. Clin Rheumatol. 1996 Jan;15 (Suppl 1):52–56. doi: 10.1007/BF03342647. [DOI] [PubMed] [Google Scholar]
  48. Taylor-Robinson D., Gilroy C. B., Thomas B. J., Keat A. C. Detection of Chlamydia trachomatis DNA in joints of reactive arthritis patients by polymerase chain reaction. Lancet. 1992 Jul 11;340(8811):81–82. doi: 10.1016/0140-6736(92)90399-n. [DOI] [PubMed] [Google Scholar]
  49. Tong C. Y., Sillis M. Detection of Chlamydia pneumoniae and Chlamydia psittaci in sputum samples by PCR. J Clin Pathol. 1993 Apr;46(4):313–317. doi: 10.1136/jcp.46.4.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Van Dis M. L., Miles D. A., Parks E. T., Razmus T. F. Information yield from a hand-held dental x-ray unit. Oral Surg Oral Med Oral Pathol. 1993 Sep;76(3):381–385. doi: 10.1016/0030-4220(93)90272-6. [DOI] [PubMed] [Google Scholar]
  51. Viitanen A. M., Arstila T. P., Lahesmaa R., Granfors K., Skurnik M., Toivanen P. Application of the polymerase chain reaction and immunofluorescence techniques to the detection of bacteria in Yersinia-triggered reactive arthritis. Arthritis Rheum. 1991 Jan;34(1):89–96. doi: 10.1002/art.1780340114. [DOI] [PubMed] [Google Scholar]
  52. Virtala M., Kirveskari J., Granfors K. HLA-B27 modulates the survival of Salmonella enteritidis in transfected L cells, possibly by impaired nitric oxide production. Infect Immun. 1997 Oct;65(10):4236–4242. doi: 10.1128/iai.65.10.4236-4242.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Wang S. P., Grayston J. T., Alexander E. R., Holmes K. K. Simplified microimmunofluorescence test with trachoma-lymphogranuloma venereum (Chlamydia trachomatis) antigens for use as a screening test for antibody. J Clin Microbiol. 1975 Mar;1(3):250–255. doi: 10.1128/jcm.1.3.250-255.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Warner T. F., Madsen J., Starling J., Wagner R. D., Taurog J. D., Balish E. Human HLA-B27 gene enhances susceptibility of rats to oral infection by Listeria monocytogenes. Am J Pathol. 1996 Nov;149(5):1737–1743. [PMC free article] [PubMed] [Google Scholar]
  55. Weyand C. M., Goronzy J. J. Immune responses to Borrelia burgdorferi in patients with reactive arthritis. Arthritis Rheum. 1989 Sep;32(9):1057–1064. doi: 10.1002/anr.1780320902. [DOI] [PubMed] [Google Scholar]
  56. van der Paardt M., van Denderen J. C., van den Brule A. J., Morré S. A., van der Horst-Bruinsma I. E., Bezemer P. D., Dijkmans B. A. Prevalence of Chlamydia trachomatis in urine of male patients with ankylosing spondylitis is not increased. Ann Rheum Dis. 2000 Apr;59(4):300–302. doi: 10.1136/ard.59.4.300. [DOI] [PMC free article] [PubMed] [Google Scholar]

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