Abstract
Background
Parvovirus B19 causes erythema infectiosum (fifth disease) in children. The virus has been associated with several autoimmune diseases and has been found in synovium or serum from patients with long-standing arthritis or other rheumatic diseases. We investigated serum and aqueous fluid samples of patients with endogenous uveitis.
Methods
Sera of 70 consecutive uveitis patients were investigated for IgG against structural proteins VP1 and VP2 and non-structural protein NS1 by western blot technique. Viral DNA in serum was assessed by quantitative PCR. Simultaneous DNA analysis was also performed on aqueous fluid samples from 11 uveitis patients and 10 patients without uveitis during routine cataract extraction.
Results
In 15 (21.4%; healthy population: 16 of 10,000) of the 70 serum samples (mean age 42.69 years, range 9–82 years; 48 women, 22 men), viral DNA was detected. IgG directed against structural protein VP1 or VP2 was found in 60 patients (85.7%; healthy population: 80%) and IgG against non-structural protein NS1 in 33 patients (47.1%; healthy population: 22%). In none of the patients was IgM antibody as a serological marker for acute parvovirus infection found. Patients with posterior uveitis (n=11) had detectable serum DNA in 54.5% (p=0.021). This group displayed the highest rate of deterioration of visual acuity (>2 Snellen lines), at 72.7% (all patients: 58.6%; p=0.219). In 2 of the 11 aqueous fluid samples, viral DNA was detected. Antibodies against parvovirus B19 were found in both samples, whereas viral DNA was absent in the serum. In the control group of 10 healthy cataract patients, 3 had detectable DNA in the aqueous humor; 1 of these 3 also had detectable levels of viral DNA in serum.
Conclusions
Prevalence of IgG antibodies against NS1 protein in serum samples and DNA in serum is increased in uveitis patients compared with the normal population, suggesting a persistent infection. The presence of DNA in aqueous humor samples shows, for the first time, persistence of parvovirus B19 in the eye in uveitis and also in healthy patients. The role of parvovirus DNA in the aqueous fluid and of IgG antibodies against NS1 in the pathogenesis of uveitis cannot be defined at present.
Similar content being viewed by others
References
Bloch-Michel E, Nussenblatt RB (1987) International uveitis study group recommendations for the evaluation of intraocular inflammatory disease. Am J Ophthalmol 103(2):234–235
Cohen BJ, Buckley MM (1988) The prevalence of antibody to human parvovirus B19 in England and Wales. J Med Microbiol 25(2):151–153
Corcoran A, Doyle S (2004) Advances in the biology, diagnosis and host-pathogen interactions of parvovirus B19. J Med Microbiol 53(Pt 6):459–475
Corridan PG, Laws DE, Morrell AJ, Murray PI (1991) Tonic pupils and human parvovirus (B19) infection. J Clin Neuroophthalmol 11(2):109–110
De Boer JH, De Keizer RJ, Kijlstra A (1993) In search of intraocular antibody production to parvo B19 virus and adenovirus in intermediate uveitis. Br J Ophthalmol 77(12):829
Dorsch S, Liebisch G, Kaufmann B, von Landenberg P, Hoffmann JH, Drobnik W, Modrow S (2002) The VP1 unique region of parvovirus B19 and its constituent phospholipase A2-like activity. J Virol 76(4):2014–2018
Eis-Hubinger AM, Reber U, Abdul-Nour T, Glatzel U, Lauschke H, Putz U (2001) Evidence for persistence of parvovirus B19 DNA in livers of adults. J Med Virol 65(2):395–401
Enders G, Dotsch J, Bauer J, Nutzenadel W, Hengel H, Haffner D, Schalasta G, Searle K, Brown KE (1998) Life-threatening parvovirus B19-associated myocarditis and cardiac transplantation as possible therapy: two case reports. Clin Infect Dis 26(2):355–358
Hemauer A, Gigler A, Searle K, Beckenlehner K, Raab U, Broliden K, Wolf H, Enders G, Modrow S (2000) Seroprevalence of parvovirus B19 NS1-specific IgG in B19-infected and uninfected individuals and in infected pregnant women. J Med Virol 60(1):48–55
Hillingso JG, Jensen IP, Tom-Petersen L (1998) Parvovirus B19 and acute hepatitis in adults. Lancet 351(9107):955–956
Jordan J, Tiangco B, Kiss J, Koch W (1998) Human parvovirus B19: prevalence of viral DNA in volunteer blood donors and clinical outcomes of transfusion recipients. Vox Sang 75(2):97–102
Kerr JR (2000) Pathogenesis of human parvovirus B19 in rheumatic disease. Ann Rheum Dis 59(9):672–683
Kerr JR, Cartron JP, Curran MD, Moore JE, Elliott JR, Mollan RA (1995) A study of the role of parvovirus B19 in rheumatoid arthritis. Br J Rheumatol 34(9):809–813
Knoll A, Louwen F, Kochanowski B, Plentz A, Stussel J, Beckenlehner K, Jilg W, Modrow S (2002) Parvovirus B19 infection in pregnancy: quantitative viral DNA analysis using a kinetic fluorescence detection system (TaqMan PCR). J Med Virol 67(2):259–266
Lehmann HW, Knoll A, Kuster RM, Modrow S (2003) Frequent infection with a viral pathogen, parvovirus B19, in rheumatic diseases of childhood. Arthritis Rheum 48(6):1631–1638
Maini R, Edelsten C (1999) Uveitis associated with parvovirus infection. Br J Ophthalmol 83(12):1403–1404
Modrow S, Dorsch S (2002) Antibody responses in parvovirus B19 infected patients. Pathol Biol (Paris) 50(5):326–331
Moffatt S, Yaegashi N, Tada K, Tanaka N, Sugamura K (1998) Human parvovirus B19 nonstructural (NS1) protein induces apoptosis in erythroid lineage cells. J Virol 72(4):3018–3028
Ozawa K, Ayub J, Kajigaya S, Shimada T, Young N (1988) The gene encoding the nonstructural protein of B19 (human) parvovirus may be lethal in transfected cells. J Virol 62(8):2884–2889
Saal JG, Steidle M, Einsele H, Muller CA, Fritz P, Zacher J (1992) Persistence of B19 parvovirus in synovial membranes of patients with rheumatoid arthritis. Rheumatol Int 12(4):147–151
Soderlund M, von Essen R, Haapasaari J, Kiistala U, Kiviluoto O, Hedman K (1997) Persistence of parvovirus B19 DNA in synovial membranes of young patients with and without chronic arthropathy. Lancet 349(9058):1063–1065
Thomas I, Di Giambattista M, Gerard C, Mathys E, Hougardy V, Latour B, Branckaert T, Laub R (2003) Prevalence of human erythrovirus B19 DNA in healthy Belgian blood donors and correlation with specific antibodies against structural and non-structural viral proteins. Vox Sang 84(4):300–307
Venturoli S, Gallinella G, Manaresi E, Gentilomi G, Musiani M, Zerbini M (1998) IgG response to the immunoreactive region of parvovirus B19 nonstructural protein by immunoblot assay with a recombinant antigen. J Infect Dis 178(6):1826–1829
von Poblotzki A, Hemauer A, Gigler A, Puchhammer-Stockl E, Heinz FX, Pont J, Laczika K, Wolf H, Modrow S (1995) Antibodies to the nonstructural protein of parvovirus B19 in persistently infected patients: implications for pathogenesis. J Infect Dis 172(5):1356–1359
Weigel-Kelley KA, Yoder MC, Srivastava A (2001) Recombinant human parvovirus B19 vectors: erythrocyte P antigen is necessary but not sufficient for successful transduction of human hematopoietic cells. J Virol 75(9):4110–4116
Weimer T, Streichert S, Watson C, Groner A (2001) High-titer screening PCR: a successful strategy for reducing the parvovirus B19 load in plasma pools for fractionation. Transfusion 41(12):1500–1504
Acknowledgements
The work was supported by the European Union (EU contract QLK2-CT-2001–0087). The authors thank Mikrogen GmbH, Munich, Germany for the donation of Recom-Blot tests, and Alexia Herrmann and Anette Rohrhofer for excellent technical assistance.
Author information
Authors and Affiliations
Corresponding author
Additional information
None of the authors has a financial interest in any of the products used or a financial relationship with the supporting organization.
Rights and permissions
About this article
Cite this article
Heinz, C., Plentz, A., Bauer, D. et al. Prevalence of parvovirus B19-specific antibodies and of viral DNA in patients with endogenous uveitis. Graefe's Arch Clin Exp Ophthalmo 243, 999–1004 (2005). https://doi.org/10.1007/s00417-005-1178-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00417-005-1178-x