Effect of Human Herpesviruses 6 and 7 Infection on the Clinical Course of Rheumatoid Arthritis / Cilvēka Herpesvīrusa 6 Un 7 Infekcijas Ietekme Uz Reimatoīdā Artrīta Klīnisko Gaitu

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Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease affecting joints and causing symmetrical chronic progressive aseptic synovitis and erosive-destructive changes. Viruses and viral infections are considered to be the main risk factors for autoimmune disease development (especially for individuals with genetic predisposition). The goal of this study was to evaluate the frequency of HHV-6 and HHV-7 persistent infection and its activity phase in RA and osteoarthritis (OA) patients, and healthy persons. We examined also the influence of HHV-6 and -7 infections on RA activity, aggressiveness, radiographical stage, and frequency of complications as well as the presence of HHV-6 infection markers in synovial fluid and synovial tissues of RA joints of affected patients. Despite the lack of significant correlation between frequency of persistent single HHV-6, single HHV-7, and concurrent HHV-6 and HHV-7 infection and RA clinical course, we found that both active and latent HHV-6 and/or HHV-7 infection increased RA activity and progression in several clinical and laboratory parameters. Regarding the severity of the course of RA, we observed also a high prevalence of RA complications in the patient group with active single HHV-6 infection and also a more severe radiographical stage in RA patients with active concurrent HHV-6 and HHV-7 infection. Moreover, viral infection markers were found in synovial fluid and synovial tissues of affected joints of RA patients. This suggests that HHV-6 and/or HHV-7 infection has effect on the disease clinical course, but virus reactivation may be a consequence of immunosuppressive treatment.

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  • Altman R. Alarcón G. Appelrouth D. Bloch D. Borenstein D. Brandt K. et al. (1990). The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand. Arthritis Rheum. 33 1601-1610.

  • Altman R. Alarcón G. Appelrouth D. Bloch D. Borenstein D. Brandt K. et al. (1991). The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthritis Rheum. 34 505-514.

  • Altman R. Asch E. Bloch D. Bole G. Borenstein D. Brandt K. et al. (1986). The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the knee. Arthritis Rheum. 29 1039-1049.

  • Alvarez-Lafuente R. Fernández-Gutiérrez de Migel S. Jover J. A. Rollihn R. Loza E. Clemente D. Lamas J. R. (2005). Potential relationship between herpes viruses and rheumatoid arthritis: Analysis with quantitative real time polymerase chain reaction. Ann. Rheum. Dis. 64 1357-1359.

  • Arnett F. C. Edworthy S. M. Bloch D. A. McShane D. J. Fries J. F. Cooper N. S. et al. (1988). The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 31 315-324.

  • Beaten D. Demetter P. Cuvelier C. Van den Bosch F. Kruithof E. Van Damme N. Verbruggen G. Mielants H. Veys E. De Keyser F. (2000). Comparative study of the synovial histology in rheumatoid arthritis spondyloarthropathy and osteoarthritis: Influence of disease duration and activity. Ann. Rheum. Dis. 59 945-953.

  • Benedetti G. Miossec P. (2014). Interleukin 17 contributes to the chronicity of inflammatory diseases such as rheumatoid arthritis. Eur. J. Immunol. 44 (2) 339-347.

  • Broccolo F. Drago F. Cassina G. Fava A. Fusetti L. Matteoli B Ceccherini-Nelli L. Sabbadini M. G. Lusso P. Parodi A. Malna M. S. (2013). Selective reactivation of human herpesvirus 6 in patients with autoimmune connective tissue diseases. J. Med. Virol. 85 1925-1934.

  • Broccolo F. Fusetti L. Ceccherini-Nelli L. (2013). Possible role of human herpesvirus 6 as a trigger of autoimmune disease. Sci. World J. 24 Article ID 867389.

  • Caselli E. Di Luca D. (2007). Molecular biology and clinical associations of Roseoloviruses human herpesvirus 6 and human herpesvirus 7. New Microbiol. 30 173-187.

  • Caselli E. Zatelli M. C. Rizzo R. Benedetti S. Martorelli D. Trasforini G. Cassai E. degli Uberti E. C. Di Luca D. Dolcetti R. (2012). Virologic and immunologic evidence supporting an association between HHV-6 and Hashimoto’s thyroiditis. PLoS Pathog. 8 (10) e1002951.

  • Chapenko S. Millers A. Nora Z. Logina I. Kukaine R. Murovska M. (2003). Correlation between HHV-6 reactivation and multiple sclerosis disease activity. J. Med. Virol. 69 (1) 111-117.

  • Choy E. H. S. Panayi S. G. (2001). Cytokine pathways and joint inflammation in rheumatoid arthritis. New Engl. J. Med. 344 907-916.

  • Costenbader K. H. Prescott J. Zee R. Y. De Vivo I. (2011). Immunosenescence and rheumatoid arthritis: Does telomere shortening predict impending disease? Autoimmun Rev. 10 (9) 569-573.

  • Davis J. M. 3rd Knutson K. L. Skinner J. A. Strausbauch M. A. Crowson C. S. Therneau T. M. Wettstein P. J. Matteson E. L. Gabriel S. E. (2012). A profile of immune response to herpesvirus is associated with radiographic joint damage in rheumatoid arthritis. Arthritis Res Ther. 14 (1) R24.

  • Emery P. (1994) The Roche Rheumatology Prize Lecture. The optimal management of early rheumatoid disease: The key to preventing disability. Brit. J. Rheumatol. 33 765-768.

  • Firestein G. S. (2003). Evolving concepts of rheumatoid arthritis. Nature 423 356-361.

  • González-Alvaro I. Ortiz A. M. Domínguez-Jiménez C. Aragón-Bodi A. Díaz Sánchez B. Sánchez-Madrid F. (2009). Inhibition of tumour necrosis factor and IL-17 production by leflunomide involves the JAK/STAT pathway. Ann. Rheum. Dis. 68 (10) 1644-1650.

  • Gottenberg J. E. Dayer J. M. Lukas C. Ducot B. Chiocchia G. Cantagrel A. Saraux A. Roux-Lombard P. Mariette X. (2012). Serum IL-6 and IL-21 are associated with markers of B cell activation and structural progression in early rheumatoid arthritis: Results from ESPOIR cohort. Ann. Rheum. Dis. 71 1243-1248.

  • Isegawa Y. Matsumoto C. Nishinaka K. Nakano K. Tanaka T. Sugimoto N. Ohshima A. (2010). PCR with quenching probes enables the rapid detection and identification of ganciclovir-resistance-causing U69 gene mutations in human herpesvirus 6. Mol. Cell. Probes. 24 (4) 167-177.

  • Kruithof E. Baeten D. De Rycke L. Vandooren B. Foell D. Roth J. Canete J. D. Boots A. M. Veys E. M. De Keyser F. (2005). Synovial histopathology of psoriatic arthritis both oligo- and polyarticular resembles spondyloarthropathy more than it does rheumatoid arthritis. Arthritis Res. Ther. 7 R569-R580.

  • Lunardi C. Bason C. Corrocher R. Puccetti A. (2005). Induction of endothelial cell damage by hCMV molecular mimicry. Review. Trends Immunol. 26 19-24.

  • Lusso P. (2006). HHV-6 and the immune system: Mechanisms of immunomodulation and viral escape. J. Clin. Virol. Suppl 1 S4-10.

  • Mackay I. R. Leskovsek N. V. Rose N. R. (2008). Cell damage and autoimmunity: A critical appraisal. Review. J Autoimmun. 30 5-11.

  • Nam J. L. Hunt L. Hensor E. M. A. Emery P. (2015). Enriching case selection for imminent RA: The use of anti-CCP antibodies in individuals with new non-specific musculoskeletal symptoms - a cohort study. Ann. Rheum. Dis. doi:10.1136/annrheumdis-207871.

  • Nard F. D. Todoerti M. Grosso V. Monti S. Breda S. Rossi S. Montecucco C. Caporali R. (2015). Risk of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing biologic treatment: Extending perspective from old to newer drugs. World J. Hepatol. 7 (3) 344-361.

  • Niewold T. B. Harrison M. J. Paget S. A. (2007). Anti-CCP antibody testing as a diagnostic and prognostic tool in rheumatoid arthritis. QJM (International Journal of Medicine) 100 (4) 193-201.

  • Nora-Krukle Z. Chapenko S. Logina I. Millers A. Platkajis A. Murovska M. (2011). Human herpesvirus 6 and 7 reactivation and disease activity in multiple sclerosis. Medicina (Kaunas) 47 (10) 527-531.

  • Pierer M. Rothe K. Quandt D. Schulz A. Rossol M. Scholz R. Baerwald C. Wagner U. (2012). Association of anticytomegalovirus seropositivity with more severe joint destruction and more frequent joint surgery in rheumatoid arthritis. Arthritis Rheum. 64 (6) 1740-1749.

  • Prober C. G. (2011). Human herpesvirus 6. Adv. Exp. Med. Biol. 697 87-90.

  • Rollín R. Alvarez-Lafuente R. Marco F. López-Durán L. Hoyas J. A. Jover J. A. Fernández-Gutiérrez B. (2009). The ubiquitin-proteasome pathway and viral infections in articular cartilage of patients with osteoarthritis. Rheumatol. Int. 29 (8) 969-972.

  • Sauerland U. Becker H. Seidel M. Schotte H. Willeke P. Schorat A. Schlüter B. Domschke W. Gaubitz M. (2005). Clinical utility of the anti-CCP assay: Experiences with 700 patients. Ann. NY Acad. Sci. 1050 314-318.

  • Sommer O. J. Kladosek A. Weiler V. Czembirek H. Boeck M. Stiskal M. (2005). Rheumatoid arthritis: A practical guide to state-of-the-art imaging image interpretation and clinical implications. Radiographics 25 (2) 381-398.

  • Trembleau S. Hoffmann M. Meyer B. Nell V. Radner H. Zauner W. Hammer J. Aichinger G. Fischer G. Smolen J. Steiner G. (2010). Immunodominant T-cell epitopes ofhnRNP-A2 associated with disease activity in patients with rheumatoid arthritis. Eur. J. Immunol. 40 (6) 1795-1808.

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

  • Van de Sande M. G. H. de Hair M. J. H. van der Leij C. Klarenbeek P. L. Bos W. H. Smith M. D. Maas M. de Vries N. van Schaardenburg D. Dijkmans B. A. C. Gerlag D. M. Tak P. P. (2011). Different stages of rheumatoid arthritis: Features of the synovium in the preclinical phase. Ann. Rheum. Dis. 70 772-777.

  • Vassilopoulos D. Calabrese L. H. (2007). Risks of immunosuppressive therapies including biologic agents in patients with rheumatic diseases and co-existing chronic viral infections. Curr. Opin. Rheumatol. 19 (6) 619-625.

  • 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 (accessed 23.02.2016).

  • Wang F.-Z. Pellet P. E. (2007). HHV-6A 6B and 7: Immunobiology and host response. In: Arvin A. Campadelli- Fiume G. Mocarski E. (eds.). Human Herpesviruses Biology. Cambridge University Press Cambridge. 1388 pp.

  • 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 (accessed 23.02.2016).

  • Zendman A. J. W. van Venrooij W. J. Pruijn G. J. M. (2006). Use and significance of anti-CCP autoantibodies in rheumatoid arthritis. Rheumatology 45 20-25.

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