Download PDF
Aktuelle Rheumatologie 2002; 27(3): 121-126
DOI: 10.1055/s-2002-33135
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Virale Infektionen als potenzielle Auslöser rheumatischer Erkrankungen

Viral Infections as Potential Triggers of Rheumatic DiseasesG.  Keyßer1
  • 1Universitätsklinikum Kröllwitz, Klinik und Poliklinik für Innere Medizin I, Halle/S.
Further Information

Publication History

Publication Date:
05 August 2002 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Eine virale Genese ist für keine der klassischen entzündlich-rheumatischen Erkrankungen bewiesen. Dennoch gibt es zahlreiche Hypothesen zur Beteiligung von Viren an der Entstehung dieser Krankheiten. Besonders intensiv untersucht wurden Retroviren und Viren der Herpesgruppe im Hinblick auf ihre Rolle bei der Entstehung der Rheumatoiden Arthritis, des Sjögren-Syndroms und des SLE. Mögliche Mechanismen für die Krankheitsentstehung sind das molekulare Mimikry, die chronische Stimulation des Immunsystems durch lymphotrope Viren und die Interferenz einer Virusinfektion mit dem programmierten Zelltod (Apoptose).

Abstract

There is currently no clearcut evidence of a viral pathogenesis of rheumatic diseases. However, there are numerous hypotheses as to the contribution of viruses to the development of rheumatic disorders. Retroviruses and viruses of the herpes family have been intensely studied with respect to their pathogenetic role in rheumatoid arthritis, Sjögren's syndrome and systemic lupus erythematosus. Molecular mimicry, the chronic stimulation of the immune system by lymphotropic viruses as well as the interference of viral infections with apoptosis are being discussed as potential mechanisms for the triggering of rheumatic diseases.

Literatur

  • 1 Asadullah K, Prosch S, Audring H, Buttnerova I, Volk H D, Sterry W. et al . A high prevalence of cytomegalovirus antigenaemia in patients with moderate to severe chronic plaque psoriasis: an association with systemic tumour necrosis factor alpha overexpression.  Br J Dermatol. 1999;  141 94-102
    CrossrefPubMedSearch in Google Scholar
  • 2 Bateman H E, Kirou K A, Paget S A, Crow M K, Yee A M. Remission of juvenile rheumatoid arthritis after infection with parvovirus B19.  J Rheumatol. 1999;  26 2482-2484
    PubMedSearch in Google Scholar
  • 3 Beilke M A, Traina-Dorge V, England J D, Blanchard J L. Polymyositis, arthritis, and uveitis in a macaque experimentally infected with human T lymphotropic virus type I.  Arthritis Rheum. 1996;  39 610-615
    PubMedSearch in Google Scholar
  • 4 Birkenfeld P, Haratz N, Klein G, Sulitzeanu D. Cross-reactivity between the EBNA-1 p107 peptide, collagen, and keratin: implications for the pathogenesis of rheumatoid arthritis.  Clin Immunol Immunopathol. 1990;  54 14-25
    CrossrefPubMedSearch in Google Scholar
  • 5 Blaschke S, Schwarz G, Moneke D, Binder L, Muller G, Reuss-Borst M. Epstein-Barr virus infection in peripheral blood mononuclear cells, synovial fluid cells, and synovial membranes of patients with rheumatoid arthritis.  J Rheumatol. 2000;  27 866-873
    PubMedSearch in Google Scholar
  • 6 Bosma T J, Etherington J, O'Shea S, Corbett K, Cottam F, Holt L. et al . Rubella virus and chronic joint disease: is there an association?.  J Clin Microbiol. 1998;  36 3524-3526
    PubMedSearch in Google Scholar
  • 7 Brand A, Griffiths D J, Herve C, Mallon E, Venables P J. Human retrovirus-5 in rheumatic disease.  J Autoimmun. 1999;  13 149-154
    CrossrefPubMedSearch in Google Scholar
  • 8 Chantler J K, Tingle A J, Petty R E. Persistent rubella virus infection associated with chronic arthritis in children.  N Engl J Med. 1985;  313 1117-1123
    PubMedSearch in Google Scholar
  • 9 Chevrel G, Calvet A, Belin V, Miossec P. Dermatomyositis associated with the presence of parvovirus B19 DNA in muscle.  Rheumatology. 2000;  39 1037-1039
    CrossrefPubMedSearch in Google Scholar
  • 10 Dawson T M, Starkebaum G, Wood B L, Willkens R F, Gown A M. Epstein-Barr virus, methotrexate, and lymphoma in patients with rheumatoid arthritis and primary Sjogren's syndrome: case series.  J Rheumatol. 2001;  28 47-53
    PubMedSearch in Google Scholar
  • 11 Edinger J W, Bonneville M, Scotet E, Houssaint E, Schumacher H R, Posnett D N. EBV gene expression not altered in rheumatoid synovia despite the presence of EBV antigen-specific T cell clones.  J Immunol. 1999;  162 3694-3701
    PubMedSearch in Google Scholar
  • 12 Einsele H, Steidle M, Muller C A, Fritz P, Zacher J, Schmidt H. et al . Demonstration of cytomegalovirus (CMV) DNA and anti-CMV response in the synovial membrane and serum of patients with rheumatoid arthritis.  J Rheumatol. 1992;  19 677-681
    PubMedSearch in Google Scholar
  • 13 Ferraro A S, Newkirk M M. Correlative studies of rheumatoid factors and anti-viral antibodies in patients with rheumatoid arthritis.  Clin Exp Immunol. 1993;  92 425-431
    PubMedSearch in Google Scholar
  • 14 Ford D K, Roza DM, Schulzer M, Reid G D, Denegri J F. Persistent synovial lymphocyte responses to cytomegalovirus antigen in some patients with rheumatoid arthritis.  Arthritis Rheum. 1987;  30 700-704
    PubMedSearch in Google Scholar
  • 15 Fox R I, Luppi M, Kang H I, Pisa P. Reactivation of Epstein-Barr virus in Sjogren's syndrome.  Springer Semin Immunopathol. 1991;  13 217-231
    PubMedSearch in Google Scholar
  • 16 Frenkel L M, Nielsen K, Garakian A, Jin R, Wolinsky J S, Cherry J D. A search for persistent rubella virus infection in persons with chronic symptoms after rubella and rubella immunization and in patients with juvenile rheumatoid arthritis.  Clin Infect Dis. 1996;  22 287-294
    PubMedSearch in Google Scholar
  • 17 Gilbert D T, Morgan O, Smikle M F, Simeon D, Barton E N. HTLV-1 associated polymyositis in Jamaica.  Acta Neurol Scand. 2001;  104 101-104
    CrossrefPubMedSearch in Google Scholar
  • 18 Griffiths D J, Cooke S P, Herve C, Rigby S P, Mallon E, Hajeer A. et al . Detection of human retrovirus 5 in patients with arthritis and systemic lupus erythematosus.  Arthritis Rheum. 1999;  42 448-454
    CrossrefPubMedSearch in Google Scholar
  • 19 Herrmann M, Hagenhofer M, Kalden J R. Retroviruses and systemic lupus erythematosus.  Immunol Rev. 1996;  152 145-156
    PubMedSearch in Google Scholar
  • 20 Hokynar K, Brunstein J, Soderlund-Venermo M, Kiviluoto O, Partio E K, Konttinen Y. et al . Integrity and full coding sequence of B19 virus DNA persisting in human synovial tissue.  J Gen Virol. 2000;  81 1017-1025
    PubMedSearch in Google Scholar
  • 21 Inoue H, Tsubota K, Ono M, Kizu Y, Mizuno F, Takada K. et al . Possible involvement of EBV-mediated alpha-fodrin cleavage for organ-specific autoantigen in Sjogren's syndrome.  J Immunol. 2001;  166 5801-5809
    PubMedSearch in Google Scholar
  • 22 James J A, Neas B R, Moser K L, Hall T, Bruner G R, Sestak A L. et al . Systemic lupus erythematosus in adults is associated with previous Epstein-Barr virus exposure.  Arthritis Rheum. 2001;  44 1122-1126
    CrossrefPubMedSearch in Google Scholar
  • 23 Keysser G, Burmester G R. Immunpathogenese entzündlich-rheumatischer Erkrankungen - Autoimmunität versus Infektion.  Z Ärztl Fortbild (Jena). 1994;  88 848-855
    PubMedSearch in Google Scholar
  • 24 Kirby B, Al-Jiffri O, Cooper R J, Corbitt G, Klapper P E, Griffiths C E. Investigation of cytomegalovirus and human herpes viruses 6 and 7 as possible causative antigens in psoriasis.  Acta Derm Venereol. 2000;  80 404-406
    PubMedSearch in Google Scholar
  • 25 Klevjer-Anderson P, Adams D S, Anderson L W, Banks K L, McGuire T C. A sequential study of virus expression in retrovirus-induced arthritis of goats.  J Gen Virol. 1984;  65 1519-1525
    PubMedSearch in Google Scholar
  • 26 Kohsaka H, Yamamoto K, Fujii H, Miura H, Miyasaka N, Nishioka K. et al . Fine epitope mapping of the human SS-B/La protein. Identification of a distinct autoepitope homologous to a viral gag polyprotein.  J Clin Invest. 1990;  85 1566-1574
    PubMedSearch in Google Scholar
  • 27 Maeda M, Maeda A, Wakiguchi H, Murakami N, Sata T, Okada T. et al . Polymyositis associated with primary cytomegalovirus infection.  Scand J Infect Dis. 2000;  32 212-214
    PubMedSearch in Google Scholar
  • 28 Maitland N, Flint S, Scully C, Crean S J. Detection of cytomegalovirus and Epstein-Barr virus in labial salivary glands in Sjogren's syndrome and non-specific sialadenitis.  J Oral Pathol Med. 1995;  24 293-298
    PubMedSearch in Google Scholar
  • 29 Moccia F. Autoimmune thrombocytopenic purpura and dermatomyositis associated with chronic hepatitis C. A therapeutic dilemma.  Ann Ital Med Int. 1998;  13 240-243
    PubMedSearch in Google Scholar
  • 30 Mountz J D, Wu J, Cheng J, Zhou T. Autoimmune disease. A problem of defective apoptosis.  Arthritis Rheum. 1994;  37 1415-1420
    PubMedSearch in Google Scholar
  • 31 Mousavi-Jazi M, Bostrom L, Lovmark C, Linde A, Brytting M, Sundqvist V A. Infrequent detection of cytomegalovirus and Epstein-Barr virus DNA in synovial membrane of patients with rheumatoid arthritis.  J Rheumatol. 1998;  25 623-628
    PubMedSearch in Google Scholar
  • 32 Murayama T, Tsuchiya N, Jisaki F, Ozaki M, Sakamuro D, Hirai K. et al . Elevated cytokine levels in synovial fluid of rheumatoid arthritis correlates with the presence of cytomegalovirus genome.  Autoimmunity. 1994;  17 333-337
    PubMedSearch in Google Scholar
  • 33 Nakagawa K, Brusic V, McColl G, Harrison L C. Direct evidence for the expression of multiple endogenous retroviruses in the synovial compartment in rheumatoid arthritis.  Arthritis Rheum. 1997;  40 627-638
    PubMedSearch in Google Scholar
  • 34 Neidhart M, Rethage J, Kuchen S, Kunzler P, Crowl R M, Billingham M E. et al . Retrotransposable L1 elements expressed in rheumatoid arthritis synovial tissue: association with genomic DNA hypomethylation and influence on gene expression.  Arthritis Rheum. 2000;  43 2634-2647
    CrossrefPubMedSearch in Google Scholar
  • 35 Nelson P N, Lever A M, Bruckner F E, Isenberg D A, Kessaris N, Hay F C. Polymerase chain reaction fails to incriminate exogenous retroviruses HTLV-I and HIV-1 in rheumatological diseases although a minority of sera cross react with retroviral antigens.  Ann Rheum Dis. 1994;  53 749-754
    PubMedSearch in Google Scholar
  • 36 Newkirk M M, Duffy K N, Paleckova A, Ivaskova E, Galianova A, Seeman J. et al . Herpes viruses in multicase families with rheumatoid arthritis.  J Rheumatol. 1995;  22 2055-2061
    PubMedSearch in Google Scholar
  • 37 Niedobitek G, Lisner R, Swoboda B, Rooney N, Fassbender H G, Kirchner T. et al . Lack of evidence for an involvement of Epstein-Barr virus infection of synovial membranes in the pathogenesis of rheumatoid arthritis.  Arthritis Rheum. 2000;  43 151-154
    CrossrefPubMedSearch in Google Scholar
  • 38 Nikkari S, Roivainen A, Hannonen P, Mottonen T, Luukkainen R, Yli-Jama T. et al . Persistence of parvovirus B19 in synovial fluid and bone marrow.  Ann Rheum Dis. 1995;  54 597-600
    PubMedSearch in Google Scholar
  • 39 Nishikai M. Coxsackievirus infection and the development of polymyositis/dermatomyositis.  Rheumatol Int. 1994;  14 43-46
    CrossrefPubMedSearch in Google Scholar
  • 40 Pachman L M, Hayford J R, Hochberg M C, Pallansch M A, Chung A, Daugherty C D. et al . New-onset juvenile dermatomyositis: comparisons with a healthy cohort and children with juvenile rheumatoid arthritis.  Arthritis Rheum. 1997;  40 1526-1533
    PubMedSearch in Google Scholar
  • 41 Richardson S J, Lopez F, Rojas S, Cho S, Holodniy M, Herndier B. et al . Multinodular polymyositis in a patient with human immunodeficiency and hepatitis C virus coinfection.  Muscle Nerve. 2001;  24 433-437
    PubMedSearch in Google Scholar
  • 42 Saal J G, Krimmel M, Steidle M, Gerneth F, Wagner S, Fritz P. et al . Synovial Epstein-Barr virus infection increases the risk of rheumatoid arthritis in individuals with the shared HLA-DR4 epitope.  Arthritis Rheum. 1999;  42 1485-1496
    CrossrefPubMedSearch in Google Scholar
  • 43 Saal J G, Steidle M, Einsele H, Muller C A, Fritz P, Zacher J. Persistence of B19 parvovirus in synovial membranes of patients with rheumatoid arthritis.  Rheumatol Int. 1992;  12 147-151
    CrossrefPubMedSearch in Google Scholar
  • 44 Sato K, Maruyama I, Maruyama Y, Kitajima I, Nakajima Y, Higaki M. et al . Arthritis in patients infected with human T lymphotropic virus type I. Clinical and immunopathologic features.  Arthritis Rheum. 1991;  34 714-721
    PubMedSearch in Google Scholar
  • 45 Scotet E, Peyrat M A, Saulquin X, Retiere C, Couedel C, Davodeau F. et al . Frequent enrichment for CD8 T cells reactive against common herpes viruses in chronic inflammatory lesions: towards a reassessment of the physiopathological significance of T cell clonal expansions found in autoimmune inflammatory processes.  Eur J Immunol. 1999;  29 973-985
    CrossrefPubMedSearch in Google Scholar
  • 46 Soderlund M von, Essen M, Haapasaari J, Kiistala U, Kiviluoto O, Hedman K. Persistence of parvovirus B19 DNA in synovial membranes of young patients with and without chronic arthropathy.  Lancet. 1997;  349 1063-1065
    CrossrefPubMedSearch in Google Scholar
  • 47 Stahl H D, Hubner B, Seidl B, Liebert U G, van der Heijden I M, Wilbrink B. et al . Detection of multiple viral DNA species in synovial tissue and fluid of patients with early arthritis.  Ann Rheum Dis. 2000;  59 342-346
    CrossrefPubMedSearch in Google Scholar
  • 48 Stransky G, Vernon J, Aicher W K, Moreland L W, Gay R E, Gay S. Virus-like particles in synovial fluids from patients with rheumatoid arthritis.  Br J Rheumatol. 1993;  32 1044-1048
    PubMedSearch in Google Scholar
  • 49 Suzuki K, Makino M, Okada Y, Kinoshita J, Yui R, Kanazawa H. et al . Exocrinopathy resembling Sjogren's syndrome induced by a murine retrovirus.  Lab Invest. 1993;  69 430-435
    PubMedSearch in Google Scholar
  • 50 Taglione E, Vatteroni M L, Martini P, Galluzzo E, Lombardini F, Delle S A. et al . Hepatitis C virus infection: prevalence in psoriasis and psoriatic arthritis.  J Rheumatol. 1999;  26 370-372
    PubMedSearch in Google Scholar
  • 51 Takeda T, Mizugaki Y, Matsubara L, Imai S, Koike T, Takada K. Lytic Epstein-Barr virus infection in the synovial tissue of patients with rheumatoid arthritis.  Arthritis Rheum. 2000;  43 1218-1225
    CrossrefPubMedSearch in Google Scholar
  • 52 Talal N, Dauphinee M J, Dang H, Alexander S S, Hart D J, Garry R F. Detection of serum antibodies to retroviral proteins in patients with primary Sjogren's syndrome (autoimmune exocrinopathy).  Arthritis Rheum. 1990;  33 774-781
    PubMedSearch in Google Scholar
  • 53 Tamm A, Ziegler T, Lautenschlager I, Nikkari S, Mottonen T, Luukkainen R. et al . Detection of cytomegalovirus DNA in cells from synovial fluid and peripheral blood of patients with early rheumatoid arthritis.  J Rheumatol. 1993;  20 1489-1493
    PubMedSearch in Google Scholar
  • 54 Tanner J E, Diaz-Mitoma F, Rooney C M, Alfieri C. Anti-interleukin-10 antibodies in patients with chronic active Epstein-Barr virus infection.  J Infect Dis. 1997;  176 1454-1461
    PubMedSearch in Google Scholar
  • 55 Thorn J J, Oxholm P, Andersen H K. High levels of complement fixing antibodies against cytomegalovirus in patients with primary Sjogren's syndrome.  Clin Exp Rheumatol. 1988;  6 71-74
    PubMedSearch in Google Scholar
  • 56 Toussirot E, Wendling D, Tiberghien P, Luka J, Roudier J. Decreased T cell precursor frequencies to Epstein-Barr virus glycoprotein Gp110 in peripheral blood correlate with disease activity and severity in patients with rheumatoid arthritis.  Ann Rheum Dis. 2000;  59 533-538
    CrossrefPubMedSearch in Google Scholar
  • 57 Tsuchiya N, Williams R CJ, Hutt-Fletcher L M. Rheumatoid factors may bear the internal image of the Fc gamma-binding protein of herpes simplex virus type I.  J Immunol. 1990;  144 4742-4748
    PubMedSearch in Google Scholar
  • 58 Venables P J, Teo C G, Baboonian C, Griffin B E, Hughes R A. Persistence of Epstein-Barr virus in salivary gland biopsies from healthy individuals and patients with Sjogren's syndrome.  Clin Exp Immunol. 1989;  75 359-364
    PubMedSearch in Google Scholar
  • 59 Weissenborn S J, Hopfl R, Weber F, Smola H, Pfister H J, Fuchs P G. High prevalence of a variety of epidermodysplasia verruciformis-associated human papillomaviruses in psoriatic skin of patients treated or not treated with PUVA.  J Invest Dermatol. 1999;  113 122-126
    CrossrefPubMedSearch in Google Scholar
  • 60 Williams R CJ, Malone C C. Studies of antibody to herpes simplex virus Fc gamma-binding protein gE in patients with rheumatoid arthritis, juvenile rheumatoid arthritis and normal controls.  Scand J Immunol. 1992;  36  801-810
    PubMedSearch in Google Scholar
  • 61 Yamano S, Renard J N, Mizuno F, Narita Y, Uchida Y, Higashiyama H. et al . Retrovirus in salivary glands from patients with Sjogren's syndrome.  J Clin Pathol. 1997;  50 223-230
    PubMedSearch in Google Scholar
  • 62 Yamazaki H, Ikeda H, Ishuzu A, Shikishima H, Kikuchi K, Wakisaka A. et al . HTLV-I env-pX transgenic rats: prototype animal model for collagen vascular diseases.  Leukemia. 1997;  11 258-259
    CrossrefPubMedSearch in Google Scholar

PD Dr. med. G. Keyßer

Universitätsklinikum Kröllwitz · Klinik und Poliklinik für Innere Medizin I

Ernst-Grube-Straße 40 · 06097 Halle/S.

Phone: 0345/557-2665

Fax: 0345/557-4934

Email: gernot.keyszer@medizin.uni-halle.de