Peripheral Blood Mononuclear Cells’ Proliferative Response to Human Parvovirus B19 Antigens in Patients with Rheumatoid Arthritis / Reimatoīdā Artrīta Slimnieku Perifēro Asiņu Mononukleāro Šūnu Proliferativā Atbilde Uz Cilvēka Parvovīrusa B19 Antigēniem

Olga Bratslavska 1 , Svetlana Kozireva 1 , Anda Kadisa 1 , 2 , 3 , Simons Svirskis 1 , Aivars Lejnieks 2 , 3 , and Modra Murovska 1
  • 1 Augusts Kirhenšteins Institute of Microbiology and Virology, Rīga Stradišņ University, Dzirciema iela 16, Rīga, LV-1007, LATVIA
  • 2 Department of Internal Diseases, Rīga Stradiņš University, Pilsoņu iela 13, Rīga, LV-1002, LATVIA
  • 3 Rīga East Clinic University Hospital, Hipokrāta iela 4, Rīga, LV-1038, LATVIA

Abstract

This study aimed to determine peripheral blood mononuclear cells’ (PBMC) proliferative response to parvovirus B19 (B19) antigens in rheumatoid arthritis (RA) patients and possible changes in proliferative response due to chemotherapy. Serum and blood samples of 52 RA patients and 25 sex and age matched healthy individuals were examined for the presence of anti-B19 IgG and IgM class antibodies and virus specific DNA sequence by the recomLine B19 test and nested polymerase chain reaction, respectively. The PBMC proliferative activity was estimated on the 3rd and 6th day of PBMC cultivation in the presence of virus and B19 VP1/VP2 peptide, using thymidine incorporation assay. On the 3rd day, PBMC response to B19 antigens was detected in 74.1% RA patients with active, in 44.8% - with remote and in 40% - with latent stage of persistent B19 infection, while in the control group the response was observed only in two individuals with active viral infection. On the 6th day, the response was found in 50% RA patients with active, 68.9% - with remote and in 80% - with latent stage of latent persistent infection as well as in 41.1% remotely infected control individuals. The highest PBMC mean stimulation indices were detected in the RA patients and control persons with active infection as well as in RA patients with latent stage of persistent viral infection. On the 3rd and 6th day, strong proliferative response was significantly more frequently observed in RA patients not receiving methotrexate treatment, compared to the patients receiving methotrexate treatment in different combinations with other drugs. RA patients had more frequent and faster response to B19 antigens than apparently healthy persons.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • Aletaha, D., Neogi, T., Silman, A.J., Funovits, J., Felson, D. T., Bingham, C. O., Birnbaum, N. S., Burmester, G. R., Bykerk, V. P., Cohen, M. D., Combe, B., Costenbader, K. H., Dougados, M., Emery, P., Ferraccioli, G., Hazes, J. M. W., Hobbs, K., Huizinga, T. W. J., Kavanaugh, A., Kay, J., Kvien, T. K., Laing, T., Mease, P., Ménard, H. A., Moreland, L. W., Naden, R. L., Pincus, T., Smolen, J. S., Stanislawska-Biernat, E., Symmons, D., Tak P. P., Upchurch, K. S., Vencovský, J., Wolfe, F., Hawker, G. (2010). Rheumatoid Arthritis Classification Criteria. Arthritis Rheum., 62 (9), 2569-2581.

  • Arnett, F. C., Edworthy, S. M., Bloch, D. A., McShane, D. J., Fries, J. F., Cooper, N. S., Healey, L. A., Kaplan, S. R., Liang, M. H., Luthra, H. S. (1988). The American Rheumatism Association 1987 revised criteria for the rheumatoid arthritis. Arthritis Rheum., 31 (3), 315-324.

  • Barah, F., Vallely, P. J., Chiswick, M. L., Cleator, G. M., Kerr, J. R. (2001). Association of human parvovirus B19 infection with acute meningoencephalitis. Lancet, 358, 729-730.

  • Broliden, K., Tolfvenstam, T., Norbeck, O. (2006). Clinical aspects of parvovirus B19 infection. J. Int. Med., 260, 285-304.

  • Franssila, R., Hokynar, K., Hedman, K. (2001). T helper cell-mediated in vitro responses of recently and remotely infected subjects to a candidate recombinant vaccine for human parvovirus B19. J. Infect. Dis., 183 (5), 805-809.

  • Franssila, R., Hedman, K. (2004) T-helper cell-mediated interferon-gamma, interleukin-10 and proliferation responses to a candidate recombinant vaccine for human parvovirus B19. Vaccine, 22 (27-28), 3809-3815.

  • Heegard, E. D., Brown, K. E. (2002). Human parvovirus B19. Clin. Microbiol. Rev., 15, 485-505.

  • Isa, A., Kasprowicz, V., Norbeck, O., Loughry, A., Jeffery, K., Broliden, K., Klenerman, P., Tolfvenstam, T., Bowness, P. (2005). Prolonged activation of virus-specific CD8+T cells after acute B19 infection. PLoS Med., 2 (12), e 343.

  • Isa, A., Norbeck, O., Hirbod, T., Lundqvist, A., Kasprowicz, V., Bowness, P, Klenerman, P., Broliden, K., Tolfvenstam, T. (2006). Aberrant cellular immune responses in humans infected persistently with parvovirus B19. J. Med. Virol., 78 (1), 129-133.

  • 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 (Kaunas), 51 (1), 18-24.

  • Kasprowicz, V., Isa, A., Tolfvenstam, T., Jeffery, K., Bowness, P., Klenerman, P. (2006). Tracking of peptide-specific CD4+ T-cell responses after an acute resolving viral infection: A study of parvovirus B19. J. Virol. 80 (22), 11209-11217.

  • 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.

  • Lindner, J., Barabas, S., Saar, K., Altmann, D., Pfister, A., Fleck, M., Deml, L., Modrow, S. (2005). CD4(+) T-cell responses against the VP1-unique region in individuals with recent and persistent parvovirus B19 infection. J. Vet. Med. B. Infect. Dis. Vet. Public Health, 52 (7-8), 356-361.

  • Moller, D. U., Ejbjerg, B. J., Hasselquist, M., Narvestad, E., M¸ller, J., Thomsen, H.S., ¨stergaard, M. (2008). Detection of bone erosions in rheumatoid arthritis wrist joints with magnetic resonance imaging, computed tomography and radiography. Arthritis Res Ther., 10 (1), R25.

  • Murai, C., Munakata, Y., Takahashi, Y., Ishii, T., Shibata, S., Murryoi, T., Funato, T., Nakamura, M., Sugamure, K., Sasaki, T. (1999). Rheumatoid arthritis after parvovirus B19 infection. Ann. Rheum. Dis., 58, 130-132.

  • Norbeck, O., Isa, A., Pöhlmann, C., Broliden, K., Kasprowicz, V., Bowness, P., Klenerman, P., Tolfvenstam, T. (2005) Sustained CD8+ T-cel responses induced after acute parvovirus B19 infection in humans. J. Virol., 79, 12117-12212.

  • Page, C., Francois, C., Goëb, V., Duverlie, G. (2015) Human parvovirus B19 and autoimmune diseases. Review of the literature and pathophysiological hypotheses. J. Clin. Virol., 72, 69-74.

  • Rogo, L. D., Mokhtari-Azad, T., Kabir, M. H., Rezaei, F. (2014). Human parvovirus B19. Acta. Virol., 58 (3), 199-213.

  • Rosenfeld, S. J., Yoshimoto, K., Kajigaya, S., Anderson, S., Young, N. S., Field, A., Warrener, P., Bansal, G., Collett, M. S. (1992). Unique region of the minor capsid protein of human parvovirus B19 is exposed on the virion surface. J. Clin. Invest., 89 (6), 2023-2029.

  • 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 (6), 3004-3009.

  • Servant-Delmas, A., Lefrere, J. J., Morinet, F., Pillet, S. (2010). Advances in human B19 erythrovirus biology. J. Virol., 84 (19), 9658-9665.

  • Streitz, M., Noutsias, M., Volkmer, R., Rohde, M., Brestrich, G., Block, A., Klippert, K., Kotsch, K., Ay, B., Hummel, M., Kühl, U., Lassner, D., Schultheiss, H. P., Volk, H. D., Kern, F. (2008). NS1 specific CD8+ T-cells with effector function and TRBV11 dominance in a patient with parvovirus B19 associated inflammatory cardiomyopathy. PLoS One, 3 (6), e2361.

  • Stahl, H. D., Pfeiffer, R., von Salis-Soglio, G., Emmrich, F. (2000). Parvovirus B19 associated mono-and oligoarticular arthritis may evolve into a chronic inflammatory arthropathy fulfilling criteria for rheumatoid arthritis or spondylarthropathy. Clin. Rheumatol., 19, 510-511.

  • Takahashi, Y., Murai, C., Shibata, S., Munakata, Y., Ishii, T., Ishii, K., Saitoh, T., Sawai, T., Sagamura, K, Sasaki, T. (1998) Human parvovirus as a causative agent for rheumatoid arthritis. Proc. Natl. Acad. Sci. USA, 95, 8227-8232.

  • Tolfvenstam, T., Oxenius, A., Price, D. A., Shacklett, B. L., Spiegel, H. M., Hedman, K., Norbeck, O. (2001). Direct ex vivo measurement of CD8+ T-lymphocyte responses to human parvovirus B19. J. Virol., 75, 540-543.

  • Van der Heijde, D. (1996). Plain X-rays in rheumatoid arthritis: overview of scoring methods, their reliability and applicability. Bailleres Clin. Rheumatol., 10, 435-453.

  • Venables, P. J. W., Maini, R. N. (2013). Clinical features of rheumatoid arthritis. In: O’Dell, J. R., Romain, P. R. (eds.). UptoDate. Wolters Kluwer Health. Available at: www.uptodate.com

  • Von Poblotzki, A., Gerdes, C., Reischl, U., Wolf, H., Modrow, S. (1996). Lymphoproliferative responses after infection with human parvovirus B19. J. Virol., 70 (10), 7327-7330.

  • Wheeless, C. R. (2012). Rheumatoid arthritis. In: Wheeless, C. R., Nunley, J. A., Urbaniak, J. R. (eds.). Wheeless’ Text of Orthopaedics. Data Trace Internet Publishing, LLC. Available at: www.wheelessonline.com

OPEN ACCESS

Journal + Issues

Search