Relationships between viruses and autoimmune diseases such as systemic lupus erythematosus (SLE) are still elusive. Recent reports demonstrated the association of some viral infections with peculiar clinical events in the general population, such as cytomegalovirus (CMV) with arterial damage and Parvovirus B19 (PV-B19) with hematologic abnormalities. We planned to look for this kind of viral imprinting in SLE, hypothesizing that traces of specific features of some viral infections might be found in some subsets of seropositive SLE patients. In 60 SLE patients recruited at our nephrologic center, serology for CMV, PV-B19, Epstein-Barr virus viral capsid antigen (EBV-VCA), Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr virus early antigen (EBV-EA) was performed. χ2 and ANOVA were employed to compare the frequency and titers of antiviral antibodies in SLE patients with groups of transplant, hemodialysis and blood donor subjects. χ2, Fisher’s test, Bonferroni and Scheffe’s test were employed to compare the different biochemical/clinical features between seropositive and seronegative SLE patients. Univariate and multivariate analysis (logistic regression models) were employed to evaluate the odds ratio (OR) of different risk factors for vascular events (including Raynaud’s phenomenon, deep venous thrombosis) and hematologic abnormalities (including severe anemia, leukopenia and thrombocytopenia). Anti-CMV (82%), anti-PV-B19 (60%), anti-EBV-VCA (92%) and EBV-EA (45%) IgG antibodies were frequent in SLE, with higher prevalence in comparison with the blood donor group and higher titers in comparison with transplant and hemodialysis groups. CMV seropositivity was a highly significant risk factor for Raynaud’s phenomenon (OR +α in univariate and multivariate analysis = 13.51 using a correction of 0.5 in case of a zero event), but not for venous vascular events (OR = 1.31). An increased though not significant risk factor was found for antiphospholipid antibodies (OR = 2.71, p = 0.19), while the presence of nephrotic syndrome during the follow-up was a significant protective factor (OR = 0.15, p = 0.035). There was no significantly increased OR for PV-B19 seropositivity in cases with severe anemia (OR = 2.09, p = 0.29). No significant associations were found with the status of EBV reactivation. In conclusion, our results support the hypothesis that viral infection may imprint the course of SLE leading to specific clinical subsets (i.e. CMV and ‘vascular’ SLE, with more frequent Raynaud’s phenomenon and a less frequent typical histological renal picture responsible for nephrotic syndrome). Further prospective studies are justified to validate these correlations, mainly dealing with associations between acute viral infections and vascular events, thus eventually leading to a better understanding of mutual relationships between viruses and SLE.

1.
Klinman DM, Stonberg AD: Systemic autoimmune disease arises from polyclonal B cell activation. J Exp Med 1987;165:1755–1760.
2.
Krieg AM, Gourley MF, Perl A: Endogenous retroviruses: Potential etologic agents in autoimmunity. FASEB J 1992;6:2537–2544.
3.
Talal N, Flescher E, Dang H: Evidence for possible retroviral involvement in autoimmune diseases. Ann Allergy 1992;69:221–223.
4.
Friedman SM, Tumang JR, Crow MK: Microbial superantigens as etiopathogenic agents in autoimmunity. Controv Clin Rheumatol 1998;19:207–216.
5.
Kahn MF: Les maladies systémiques sont-elles d’origine infectieuse? Rev Prat 1994;44:911–914.
6.
Schattner A, Rager-Zisman B: Virus-induced autoimmunity. Rev Infect Dis 1990;12:204–218.
7.
Tosato G, Blaese RM, Yarchoan R: Relationship between immunoglobulin production and immortalization by Ebstein-Barr virus. J Immunol 1985;135:959–964.
8.
Sasaki T, Muryoi T, Sechiguchi Y, Tamate E, Yoshinaga K, Kitagawa Y: Monoclonal human anti-DNA antibodies from EB virus-transformed lymphocytes of systemic lupus erythematosus (SLE) patients. J Clin Immunol 1985;5:246–253.
9.
Newkirk MM, Tsoukas C: Effect of ultraviolet irradiation on selected host cell proteins including RO/SS-A and Epstein-Barr virus in cultured lymphoblastoid cell lines. J Autoimmun 1992;5:511–525.
10.
Lebner MR, Andrews NC, Miller G, Steitz JA: Two small RNAs encoded by Epstein-Barr virus and complexed with protein are precipitated by antibodies from patients with systemic lupus erythematosus. Proc Nat Acad Sci USA 1981;78:805–809.
11.
Marchini B, Dolcher MP, Sabbatini A, Klein G, Migliorini P: Immune response to different sequences of the EBNA 1 molecule in Epstein-Barr virus-related disorders and in autoimmune diseases. J Autoimmun 1994;7:179–191.
12.
Cope AP, Jones A, Brozovic M, Shalfi MS, Maini RM: Possible induction of systemic lupus erythematosus by human parvovirus. Ann Rheum Dis 1992;51:803–804.
13.
Soloninka CA, Anderson MJ, Laskin CA: Anti-DNA and antilymphocyte antibodies during acute infection with human Parvovirus B19. J Rheumatol 1989;16:777–781.
14.
Nesher G, Osborn TG, Moore TL: Parvovirus infection mimicking systemic lupus erythematosus. Semin Arthritis Rheum 1995;24:297–303.
15.
Chassagne P, Mejjad O, Gourmeien O, Moore N, Le Loet X, Deshayes P: Exacerbation of systemic lupus erythematosus during human parvovirus B19 infection. Br J Rheumatol 1993;32:158–159.
16.
Sasaki T, Takahashi Y, Yoshinaga K, Sugamura K: An association between human Parvovirus B-19 infection and autoantibody production. J Rheumatol 1989;16:708–709.
17.
Vigeant B, Ménard H-A, Boire G: Chronic modulation of the autoimmune response following parvovirus B19 infection. J Rheumatol 1994;21:1165–1167.
18.
Bulpitt KJ, Brahn E: Systemic lupus erythematosus and concurrent cytomegalovirus vasculitis: Diagnosis by antemortem skin biopsy. J Rheumatol 1989;16:677–680.
19.
Vasquez V, Barzaga RA, Cunha BA: Cytomegalovirus-induced flare of systemic lupus erythematosus. Heart Lung 1992;21:407–408.
20.
Speir E, Modali R, Huang E-S, Leon MB, Shawl F, Finkel T, Epstein SE: Potential role of human cytomegalovirus and p53 interaction in coronary restenosis. Science 1994;265:391–394.
21.
Zhou YF, Leon MBL, Waclawiw MA, Popma JJ, Yu ZX, Finkel T, Epstein SE: Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy. N Engl J Med 1996;335:624–630.
22.
Southern P, Oldstone MBA: Medical consequences of persistent viral infection. N Engl J Med 1986;314:359–367.
23.
Rotbart HA: Human parvovirus infection. Annu Rev Med 1990;41:25–34.
24.
White DG, Mortimer PP, Blake DR, Woolf AD, Cohen BJ, Bacon PA: Human parvovirus arthropathy. Lancet 1985;i:419–421.
25.
Loizou S, Cazabon JK, Walport MJ, Tait D, So AK: Similarities of specificity and cofactor dependence in serum antiphospholipid anti- bodies from patients with human parvovirus B19 infection and from those with systemic lupus erythematosus. Arthritis Rheum 1997;40:103–108.
26.
Tan EM, Cohen AS, Fries JF: The revised criteria for the classification of SLE. Arthritis Rheum 1987;30:382–388.
27.
Churg J, Sobin LH: Lupus Nephritis; in Churg J (ed): Renal Disease. Classification and Atlas of Glomerular Diseases. New York, Igaku-Shoin, 1982, pp 127–149.
28.
Exner T, Rickard K, Kronenberg H: A sensitive test demonstrating lupus anticoagulant and its behavioural patterns. Br J Haematol 1978;40:143–151.
29.
Harris EN, Gharavi AE, Boey ML, Patel BM, Mackworth-Young CG, Loizou S, Hughes GRV: Anticardiolipin antibodies: Detection by radioimmunoassay and association with thrombosis in sistemic lupus erythematosus. Lancet 1983;ii:1211–1214.
30.
Mantero G, Zonaro A, Albertini A, Bertolo P, Primi D: DNA enzyme immunoassay: General method for detecting products of polymerase chain reaction. Clin Chem 1991;37:442–447.
31.
Hay EM: Systemic lupus erithematosus. Baillières Clin Rheumatol 1995;9:437–470.
32.
Kitagawa H, Iho S, Yokochi T, Hosino T: Detection of antibodies to the Epstein-Barr virus nuclear antigens in the sera from patients with systemic lupus erythematosus. Immunol Lett 1988;17:249–252.
33.
Origgi L, Perego R, Hu C, Bertitti E, d’Agostino P, Asero R, Riboldi P: Anti-Epstein-Barr virus antibodies in systemic lupus erythematosus. Boll Ist Sieroter Milan 1988;67:116–122.
34.
Zhu J: Cytomegalovirus infection induces expression of 60 KD/RO antigen on human cheratinocytes. Lupus 1995;4:396–406.
35.
Hughes GRV: The antiphospholipid syndrome: Ten years on. Lancet 1993;342:341–344.
36.
Sneddon JB: Cerebro-vascular lesions and livedo reticularis. Br J Dermatol 1965;77:180– 184.
37.
Steen VD: Clinical manifestations of systemic sclerosis. Semin Cutan Med Surg 1998;17:48–54.
38.
Amigo M-C, Garcia-Torres R, Robles M, Bochicchio T, Reyes PA: Renal involvement in primary antiphospholipid syndromes. J Rheumatol 1992;19:1181–1185.
39.
Scolari F, Savoldi S, Costantino E, Spitti C, Franceschini F, Tardanico R, Morassi L, Maiorca R: Antiphospholipid antibodies. Nephrol Dial Transplant 1993;8:1274–1276.
40.
Mandreoli M, Zucchelli P: Renal vascular disease in patients with primary antiphospholipid antibodies. Nephrol Dial Transplant 1993;8:1277–1280.
41.
Rosove MH, Brewer PMC: Antiphospholipid thrombosis: Clinical course after the 1st thrombotic event in 70 patients. Ann Intern Med 1992;117:303–308.
42.
Triplett DA: Antiphospholipid and thrombosis: A consequence, coincidence or cause? Arch Pathol Lab Med 1993;117:78–88.
43.
Schattner A, Sthoeger Z, Geltner D: Effect of acute cytomegalovirus infection or drug-induced SLE. Postgrad Med J 1994;70:738–740.
44.
Lord PCW, Rothschild CB, de Rose RT, Kilpatrick BA: Human cytomegalovirus RNA immunoprecipitated by multiple systemic lupus erythematosus antisera. J Med Virol 1989;70:2383–2396.
45.
Stancek D, Bovensky J: Enhancement of Epstein-Barr virus antibody production in systemic lupus erythematosus patients. Acta Virol 1979;23:168–169.
46.
Milman G, Scott AL, Cho MS, Hartman SC, Ades DK, Hayward GS, Ki P-F, August JT, Hayward SD: Carboxyl-terminal domain of the Epstein-Barr virus nuclear antigen is highly immunogenic in man. Proc Natl Acad Sci USA 1985;82:6300–6304.
47.
Ngou Y, Graafland N, Segondy M: Antibodies against polypeptides of purified Epstein-Barr virus in sera from patients with connective tissue diseases: Altered immune response to EBNA in patient with SLE. J Autoimmun 1992;5:243–249.
48.
Petersen J, Rhodes G, Roudier J, Vaughan JH: Altered immune response to glycine-rich sequences of Epstein-Barr nuclear antigen-1 in patients with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Rheum 1990;33:993–999.
49.
Duffy KNW, Duffy CM, Gladman DD: Infection and disease activity in systemic lupus erythematosus: A review of hospitalized patients. J Rheumatol 1991;18:1180–1184.
50.
Niopoulos AG, Tsokos GC: Immunopathogenesis and spectrum of infections in systemic lupus erythematosus. Semin Arthritis Rheum 1996;25:318–336.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.