Frequency and significance of parvovirus B19 infection in patients with rheumatoid arthritis Open Access

Abstract

The present study aims to clarify the possible involvement of parvovirus B19 (B19V) infection in rheumatoid arthritis (RA) pathogenesis by investigating the presence of B19V infection markers (genomic sequences and virus-specific antibodies) in association with the level of cytokines and RA clinical activity and aggressiveness. A total of 118 RA patients and 49 age- and sex-matched healthy volunteers were enrolled in the study. Nested PCR was used to detect B19V sequences in whole blood and cell-free plasma DNA, ELISA to detect virus-specific antibodies and cytokine levels in plasma and recomLine dot blot assay for antibodies to separate B19V antigens. The detection frequency of B19V DNA was higher in patients with RA (25.4 %) in comparison with healthy persons (18.4 %). B19V DNA in cell-free plasma (B19p) was detected significantly often in RA patients in comparison with healthy controls (13.6 vs 2 %; =0.0002). RA B19p patients had higher disease activity and aggressiveness, decreased haemoglobin and increased erythrocyte sedimentation rates. IL-6 plasma levels were significantly higher in RA patients than in controls. Within the RA patients’ group the IL-6 level was significantly increased in B19p patients with disease activity scores of DAS28>5.2, high C-reactive protein and low haemoglobin. Contrary to the healthy controls, the majority of RA B19p patients did not have antibodies to VP-1S (VP1u) and VP-N (N-terminal half of structural proteins VP1 and VP2), which correspond to the epitopes of neutralizing antibodies. These results indicate that B19V infection at least in some patients is involved in RA pathogenesis.

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2016-12-16
2024-03-28
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References

  1. Arabski M., Fudala R., Koza A., Wasik S., Futoma-Koloch B., Bugla-Ploskonska G., Kaca W. 2012; The presence of anti-LPS antibodies and human serum activity against Proteus mirabilis S/R forms in correlation with TLR4 (Thr399Ile) gene polymorphism in rheumatoid arthritis. Clin Biochem 45:1374–1382 [View Article][PubMed]
    [Google Scholar]
  2. Arleevskaya M. I., Gabdoulkhakova A. G., Filina Y. V., Miftakhova R. R., Bredberg A., Tsybulkin A. P. 2014; A transient peak of infections during onset of rheumatoid arthritis: a 10-year prospective cohort study. BMJ Open 4:e005254 [View Article][PubMed]
    [Google Scholar]
  3. Azzi A., Manaresi E., Zakrzewska K., DeSantis R., Musiani M., Zerbini M. 2004; Antibody response to B19 parvovirus VP1 and VP2 linear epitopes in patients with haemophilic arthritis. J Med Virol 72:679–682 [View Article][PubMed]
    [Google Scholar]
  4. Bartold P. M., Marino V., Cantley M., Haynes D. R. 2010; Effect of Porphyromonas gingivalis-induced inflammation on the development of rheumatoid arthritis. J Clin Periodontol 37:405–411 [View Article][PubMed]
    [Google Scholar]
  5. Berry P. J., Gray E. S., Porter H. J., Burton P. A. 1992; Parvovirus infection of the human fetus and newborn. Semin Diagn Pathol 9:4–12[PubMed]
    [Google Scholar]
  6. Bertoni E., Rosati A., Zanazzi M., Azzi A., Zakrzewska K., Guidi S., Fanci R., Salvadori M. 1997; Aplastic anemia due to B19 parvovirus infection in cadaveric renal transplant recipients: an underestimated infectious disease in the immunocompromised host. J Nephrol 10:152–156[PubMed]
    [Google Scholar]
  7. Bratslavska O., Kozireva S., Baryshev M., Russev R., Alexandrov M., Uzameckis D., Todorova K., Dimitrov P., Murovska M. 2015; Parvovirus B19 infection increases proliferative activity of non-permissive cells. Virologie 68:49–58
    [Google Scholar]
  8. Brown T., Anand A., Ritchie L. D., Clewley J. P., Reid T. M. 1984; Intrauterine parvovirus infection associated with hydrops fetalis. Lancet 2:1033–1034[PubMed] [CrossRef]
    [Google Scholar]
  9. Caliskan R., Masatlioglu S., Aslan M., Altun S., Saribas S., Ergin S., Uckan E., Koksal V., Oz V. et al. 2005; The relationship between arthritis and human parvovirus B19 infection. Rheumatol Int 26:7–11 [View Article][PubMed]
    [Google Scholar]
  10. Chapenko S., Krumina A., Logina I., Rasa S., Chistjakovs M., Sultanova A., Viksna L., Murovska M. 2012; Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Adv Virol 2012:205085 [View Article][PubMed]
    [Google Scholar]
  11. Chen Y. S., Chou P. H., Li S. N., Tsai W. C., Lin K. H., Tsai K. B., Yen J. H., Liu H. W. 2006; Parvovirus B19 infection in patients with rheumatoid arthritis in Taiwan. J Rheumatol 33:887–891[PubMed]
    [Google Scholar]
  12. Chorba T., Coccia P., Holman R. C., Tattersall P., Anderson L. J., Sudman J., Young N. S., Kurczynski E., Saarinen U. M. et al. 1986; The role of parvovirus B19 in aplastic crisis and erythema infectiosum (fifth disease). J Infect Dis 154:383–393 [View Article][PubMed]
    [Google Scholar]
  13. Clewley J. P., Cohen B. J., Field A. M. 1987; Detection of parvovirus B19 DNA, antigen, and particles in the human fetus. J Med Virol 23:367–376 [View Article][PubMed]
    [Google Scholar]
  14. Cohen B. J., Beard S., Knowles W. A., Ellis J. S., Joske D., Goldman J. M., Hewitt P., Ward K. N. 1997; Chronic anemia due to parvovirus B19 infection in a bone marrow transplant patient after platelet transfusion. Transfusion 37:947–952 [View Article][PubMed]
    [Google Scholar]
  15. Corcoran A., Doyle S., Waldron D., Nicholson A., Mahon B. P. 2000; Impaired gamma interferon responses against parvovirus B19 by recently infected children. J Virol 74:9903–9910 [View Article][PubMed]
    [Google Scholar]
  16. Cotmore S. F., McKie V. C., Anderson L. J., Astell C. R., Tattersall P. 1986; Identification of the major structural and nonstructural proteins encoded by human parvovirus B19 and mapping of their genes by procaryotic expression of isolated genomic fragments. J Virol 60:548–557[PubMed]
    [Google Scholar]
  17. De Re V., De Vita S., Battistella V., Marzotto A., Libra M., Ferraccioli G., Boiocchi M. 2002; Absence of human parvovirus B19 DNA in myoepithelial sialadenitis of primary Sjögren's syndrome. Ann Rheum Dis 61:855–856 [View Article][PubMed]
    [Google Scholar]
  18. De Stefano R., Manganelli S., Frati E., Selvi E., Azzi A., Zakrzewska K., Marcolongo R. 2003; No association between human parvovirus B19 infection and Sjögren's syndrome. Ann Rheum Dis 62:86–87 [View Article][PubMed]
    [Google Scholar]
  19. Dijkmans B. A., van Elsacker-Niele A. M., Salimans M. M., van Albada-Kuipers G. A., de Vries E., Weiland H. T. 1988; Human parvovirus B19 DNA in synovial fluid. Arthritis Rheum 31:279–281 [View Article][PubMed]
    [Google Scholar]
  20. Durigon E. L., Erdman D. D., Gary G. W., Pallansch M. A., Torok T. J., Anderson L. J. 1993; Multiple primer pairs for polymerase chain reaction (PCR) amplification of human parvovirus B19 DNA. J Virol Methods 44:155–165 [View Article][PubMed]
    [Google Scholar]
  21. Heegaard E. D., Laub Petersen B. 2000; Parvovirus B19 transmitted by bone marrow. Br J Haematol 111:659–661 [View Article][PubMed]
    [Google Scholar]
  22. Hitchon C. A., Chandad F., Ferucci E. D., Willemze A., Ioan-Facsinay A., van der Woude D., Markland J., Robinson D., Elias B. et al. 2010; Antibodies to Porphyromonas gingivalis are associated with anticitrullinated protein antibodies in patients with rheumatoid arthritis and their relatives. J Rheumatol 37:1105–1112 [View Article][PubMed]
    [Google Scholar]
  23. Hsu T. C., Tsay G. J. 2001; Human parvovirus B19 infection in patients with systemic lupus erythematosus. Rheumatology 40:152–157 [View Article][PubMed]
    [Google Scholar]
  24. Hsu T. C., Tzang B. S., Huang C. N., Lee Y. J., Liu G. Y., Chen M. C., Tsay G. J. 2006; Increased expression and secretion of interleukin-6 in human parvovirus B19 non-structural protein (NS1) transfected COS-7 epithelial cells. Clin Exp Immunol 144:152–157 [View Article][PubMed]
    [Google Scholar]
  25. Juhl D., Steppat D., Görg S., Hennig H. 2014; Parvovirus b19 infections and blood counts in blood donors. Transfus Med Hemother 41:52–59 [View Article][PubMed]
    [Google Scholar]
  26. Kakurina N., Kadisa A., Lejnieks A., Mikazane H., Kozireva S., Murovska M. 2015; Use of exploratory factor analysis to ascertain the correlation between the activities of rheumatoid arthritis and infection by human parvovirus B19. Medicina 51:18–24 [View Article][PubMed]
    [Google Scholar]
  27. Kerr J. R. 2000; Pathogenesis of human parvovirus B19 in rheumatic disease. Ann Rheum Dis 59:672–683 [View Article][PubMed]
    [Google Scholar]
  28. Kerr J. R., Cartron J. P., Curran M. D., Moore J. E., Elliott J. R., Mollan R. A. 1995; A study of the role of parvovirus B19 in rheumatoid arthritis. Br J Rheumatol 34:809–813[PubMed] [CrossRef]
    [Google Scholar]
  29. Kerr J. R., Barah F., Mattey D. L., Laing I., Hopkins S. J., Hutchinson I. V., Tyrrell D. A. 2001; Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue. J Gen Virol 82:3011–3019 [View Article][PubMed]
    [Google Scholar]
  30. Kerr J. R., Cunniffe V. S., Kelleher P., Coats A. J., Mattey D. L. 2004; Circulating cytokines and chemokines in acute symptomatic parvovirus B19 infection: negative association between levels of pro-inflammatory cytokines and development of B19-associated arthritis. J Med Virol 74:147–155 [View Article][PubMed]
    [Google Scholar]
  31. Kinney J. S., Anderson L. J., Farrar J., Strikas R. A., Kumar M. L., Kliegman R. M., Sever J. L., Hurwitz E. S., Sikes R. K. 1988; Risk of adverse outcomes of pregnancy after human parvovirus B19 infection. J Infect Dis 157:663–667 [View Article][PubMed]
    [Google Scholar]
  32. Kozireva S. V., Zestkova J. V., Mikazane H. J., Kadisa A. L., Kakurina N. A., Lejnieks A. A., Danilane I. N., Murovska M. F. 2008; Incidence and clinical significance of parvovirus B19 infection in patients with rheumatoid arthritis. J Rheumatol 35:1265–1270[PubMed]
    [Google Scholar]
  33. Kurtzman G. J., Cohen B. J., Field A. M., Oseas R., Blaese R. M., Young N. S. 1989; Immune response to B19 parvovirus and an antibody defect in persistent viral infection. J Clin Invest 84:1114–1123 [View Article][PubMed]
    [Google Scholar]
  34. Lefrère J. J., Couroucé A. M., Bertrand Y., Girot R., Soulier J. P. 1986; Human parvovirus and aplastic crisis in chronic hemolytic anemias: a study of 24 observations. Am J Hematol 23:271–275 [View Article][PubMed]
    [Google Scholar]
  35. Lehmann H. W., Lutterbüse N., Plentz A., Akkurt I., Albers N., Hauffa B. P., Hiort O., Schoenau E., Modrow S. 2008; Association of parvovirus B19 infection and Hashimoto's thyroiditis in children. Viral Immunol 21:379–383 [View Article][PubMed]
    [Google Scholar]
  36. Leisi R., Ruprecht N., Kempf C., Ros C. 2013; Parvovirus B19 uptake is a highly selective process controlled by VP1u, a novel determinant of viral tropism. J Virol 87:13161–13167 [View Article][PubMed]
    [Google Scholar]
  37. Lui S. L., Luk W. K., Cheung C. Y., Chan T. M., Lai K. N., Peiris J. S. 2001; Nosocomial outbreak of parvovirus B19 infection in a renal transplant unit. Transplantation 71:59–64[PubMed] [CrossRef]
    [Google Scholar]
  38. Magnusson M., Brisslert M., Zendjanchi K., Lindh M., Bokarewa M. I. 2010; Epstein-Barr virus in bone marrow of rheumatoid arthritis patients predicts response to rituximab treatment. Rheumatology 49:1911–1919 [View Article][PubMed]
    [Google Scholar]
  39. Manaresi E., Gallinella G., Zerbini M., Venturoli S., Gentilomi G., Musiani M. 1999; IgG immune response to B19 parvovirus VP1 and VP2 linear epitopes by immunoblot assay. J Med Virol 57:174–178 [View Article][PubMed]
    [Google Scholar]
  40. Manaresi E., Gallinella G., Venturoli S., Zerbini M., Musiani M. 2004; Detection of parvovirus B19 IgG: choice of antigens and serological tests. J Clin Virol 29:51–53 [View Article][PubMed]
    [Google Scholar]
  41. Manicourt D. H., Triki R., Fukuda K., Devogelaer J. P., Nagant de Deuxchaisnes C., Thonar E. J. 1993; Levels of circulating tumor necrosis factor alpha and interleukin-6 in patients with rheumatoid arthritis. Relationship to serum levels of hyaluronan and antigenic keratan sulfate. Arthritis Rheum 36:490–499 [View Article][PubMed]
    [Google Scholar]
  42. McInnes I. B., Schett G. 2011; The pathogenesis of rheumatoid arthritis. N Engl J Med 365:2205–2219 [View Article][PubMed]
    [Google Scholar]
  43. Meron M. K., Amital H., Shepshelovich D., Barzilai O., Ram M., Anaya J. M., Gerli R., Bizzaro N., Nicola B., Shoenfeld Y. 2010; Infectious aspects and the etiopathogenesis of rheumatoid arthritis. Clin Rev Allergy Immunol 38:287–291 [View Article][PubMed]
    [Google Scholar]
  44. Millá F., Feliu E., Ribera J. M., Juncà J., Flores A., Vidal J., Zarco M. A., Masat T. 1993; Electron microscopic identification of parvovirus virions in erythroid and granulocytic-line cells in a patient with human parvovirus B19 induced pancytopenia. Leuk Lymphoma 10:483–487 [View Article][PubMed]
    [Google Scholar]
  45. Moore T. L., Bandlamudi R., Alam S. M., Nesher G. 1999; Parvovirus infection mimicking systemic lupus erythematosus in a pediatric population. Semin Arthritis Rheum 28:314–318 [View Article][PubMed]
    [Google Scholar]
  46. Morey A. L., Fleming K. A. 1992; Immunophenotyping of fetal haemopoietic cells permissive for human parvovirus B19 replication in vitro. Br J Haematol 82:302–309 [View Article][PubMed]
    [Google Scholar]
  47. Mourgues C., Henquell C., Tatar Z., Pereira B., Nourisson C., Tournadre A., Soubrier M., Couderc M. 2016; Monitoring of Epstein-Barr virus (EBV)/cytomegalovirus (CMV)/varicella-zoster virus (VZV) load in patients receiving tocilizumab for rheumatoid arthritis. Joint Bone Spine 83:412–415 [View Article][PubMed]
    [Google Scholar]
  48. Musiani M., Pasini P., Zerbini M., Gentilomi G., Roda A., Gallinella G., Manaresi E., Venturoli S. 1999; Prenatal diagnosis of parvovirus B19-induced hydrops fetalis by chemiluminescence in situ hybridization. J Clin Microbiol 37:2326–2329[PubMed]
    [Google Scholar]
  49. Nikkari S., Roivainen A., Hannonen P., Möttönen T., Luukkainen R., Yli-Jama T., Toivanen P. 1995; Persistence of parvovirus B19 in synovial fluid and bone marrow. Ann Rheum Dis 54:597–600 [View Article][PubMed]
    [Google Scholar]
  50. Oğuz F., Akdeniz C., Unüvar E., Küçükbasmaci O., Sidal M. 2002; Parvovirus B19 in the acute arthropathies and juvenile rheumatoid arthritis. J Paediatr Child Health 38:358–362[PubMed] [CrossRef]
    [Google Scholar]
  51. Okada Y., Kim K., Han B., Pillai N. E., Ong R. T., Saw W. Y., Luo M., Jiang L., Yin J. et al. 2014; Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations. Hum Mol Genet 23:6916–6926 [View Article][PubMed]
    [Google Scholar]
  52. Ozawa K., Young N. 1987; Characterization of capsid and noncapsid proteins of B19 parvovirus propagated in human erythroid bone marrow cell cultures. J Virol 61:2627–2630[PubMed]
    [Google Scholar]
  53. Ozawa K., Ayub J., Hao Y. S., Kurtzman G., Shimada T., Young N. 1987; Novel transcription map for the B19 (human) pathogenic parvovirus. J Virol 61:2395–2406[PubMed]
    [Google Scholar]
  54. Pfrepper K. I., Enders M., Motz M. 2005; Human parvovirus B19 serology and avidity using a combination of recombinant antigens enables a differentiated picture of the current state of infection. J Vet Med B Infect Dis Vet Public Health 52:362–365 [View Article][PubMed]
    [Google Scholar]
  55. Ramos-Casals M., Cervera R., García-Carrasco M., Vidal J., Trejo O., Jiménez S., Costa J., Font J., Ingelmo M. 2000; Cytopenia and past human parvovirus B19 infection in patients with primary Sjögren's syndrome. Semin Arthritis Rheum 29:373–378 [View Article][PubMed]
    [Google Scholar]
  56. Reid D. M., Reid T. M., Brown T., Rennie J. A., Eastmond C. J. 1985; Human parvovirus-associated arthritis: a clinical and laboratory description. Lancet 1:422–425[PubMed] [CrossRef]
    [Google Scholar]
  57. Saikawa T., Anderson S., Momoeda M., Kajigaya S., Young N. S. 1993; Neutralizing linear epitopes of B19 parvovirus cluster in the VP1 unique and VP1-VP2 junction regions. J Virol 67:3004–3009[PubMed]
    [Google Scholar]
  58. Sato H., Hirata J., Kuroda N., Shiraki H., Maeda Y., Okochi K. 1991; Identification and mapping of neutralizing epitopes of human parvovirus B19 by using human antibodies. J Virol 65:5485–5490[PubMed]
    [Google Scholar]
  59. Scott D. L., Wolfe F., Huizinga T. W. 2010; Rheumatoid arthritis. Lancet 376:1094–1108 [View Article][PubMed]
    [Google Scholar]
  60. Sève P., Ferry T., Koenig M., Cathebras P., Rousset H., Broussolle C. 2005; Lupus-like presentation of parvovirus B19 infection. Semin Arthritis Rheum 34:642–648 [View Article][PubMed]
    [Google Scholar]
  61. Shimamoto K., Ito T., Ozaki Y., Amuro H., Tanaka A., Nishizawa T., Son Y., Inaba M., Nomura S. 2013; Serum interleukin 6 before and after therapy with tocilizumab is a principal biomarker in patients with rheumatoid arthritis. J Rheumatol 40:1074–1081 [View Article][PubMed]
    [Google Scholar]
  62. Söderlund M., Brown C. S., Spaan W. J., Hedman L., Hedman K. 1995; Epitope type-specific IgG responses to capsid proteins VP1 and VP2 of human parvovirus B19. J Infect Dis 172:1431–1436 [View Article][PubMed]
    [Google Scholar]
  63. Söderlund 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 349:1063–1065 [View Article][PubMed]
    [Google Scholar]
  64. Söderlund-Venermo M., Hokynar K., Nieminen J., Rautakorpi H., Hedman K. 2002; Persistence of human parvovirus B19 in human tissues. Pathol Biol 50:307–316 [View Article][PubMed]
    [Google Scholar]
  65. Stabler T., Piette J. C., Chevalier X., Marini-Portugal A., Kraus V. B. 2004; Serum cytokine profiles in relapsing polychondritis suggest monocyte/macrophage activation. Arthritis Rheum 50:3663–3667 [View Article][PubMed]
    [Google Scholar]
  66. Takahashi Y., Murai C., Shibata S., Munakata Y., Ishii T., Ishii K., Saitoh T., Sawai T., Sugamura K., Sasaki T. 1998; Human parvovirus B19 as a causative agent for rheumatoid arthritis. Proc Natl Acad Sci U S A 95:8227–8232 [View Article][PubMed]
    [Google Scholar]
  67. Tzang B. S., Chiu C. C., Tsai C. C., Lee Y. J., Lu I. J., Shi J. Y., Hsu T. C. 2009a; Effects of human parvovirus B19 VP1 unique region protein on macrophage responses. J Biomed Sci 16:13 [View Article]
    [Google Scholar]
  68. Tzang B. S., Tsai C. C., Tsay G. J., Wang M., Sun Y. S., Hsu T. C. 2009b; Anti-human parvovirus B19 nonstructural protein antibodies in patients with rheumatoid arthritis. Clin Chim Acta 405:76–82 [View Article]
    [Google Scholar]
  69. Voll R. E., Roth E. A., Girkontaite I., Fehr H., Herrmann M., Lorenz H. M., Kalden J. R. 1997; Histone-specific Th0 and Th1 clones derived from systemic lupus erythematosus patients induce double-stranded DNA antibody production. Arthritis Rheum 40:2162–2171 [View Article][PubMed]
    [Google Scholar]
  70. von Poblotzki A., Gigler A., Lang B., Wolf H., Modrow S. 1995; Antibodies to parvovirus B19 NS-1 protein in infected individuals. J Gen Virol 76:519–527 [View Article][PubMed]
    [Google Scholar]
  71. Wang J., Zhang W., Liu H., Wang D., Wang W., Li Y., Wang Z., Wang L., Zhang W., Huang G. 2010; Parvovirus B19 infection associated with Hashimoto's thyroiditis in adults. J Infect 60:360–370 [View Article][PubMed]
    [Google Scholar]
  72. White D. G., Woolf A. D., Mortimer P. P., Cohen B. J., Blake D. R., Bacon P. A. 1985; Human parvovirus arthropathy. Lancet 1:419–421[PubMed] [CrossRef]
    [Google Scholar]
  73. Zuffi E., Manaresi E., Gallinella G., Gentilomi G. A., Venturoli S., Zerbini M., Musiani M. 2001; Identification of an immunodominant peptide in the parvovirus B19 VP1 unique region able to elicit a long-lasting immune response in humans. Viral Immunol 14:151–158 [View Article][PubMed]
    [Google Scholar]
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