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Clinical Rheumatology

, Volume 36, Issue 4, pp 863–869 | Cite as

Human cytomegalovirus (HCMV) UL44 and UL57 specific antibody responses in anti-HCMV-positive patients with systemic sclerosis

  • Emmanouela Marou
  • Christos Liaskos
  • Theodora Simopoulou
  • Georgios Efthymiou
  • Efthymios Dardiotis
  • Christina Katsiari
  • Thomas Scheper
  • Wolfgang Meyer
  • Georgios Hadjigeorgiou
  • Dimitrios P. Bogdanos
  • Lazaros I. Sakkas
Original Article

Abstract

The role of human cytomegalovirus (HCMV) has been postulated as a trigger of systemic sclerosis (SSc). The aim of the study was to assess the prevalence of antibodies against HCMV UL44 and UL57 antigens not tested in the past. Sixty SSc patients, 40 multiple sclerosis and 17 normal controls (NCs), all anti-HCMV positive, were tested by immunoblotting. Reactivity to HCMV antigens, expressed as arbitrary units (AUs), was assessed for correlation with clinical and immunological parameters, including types of SSc-related autoantibodies. Anti-UL44 and anti-UL57 HCMV antibodies were present in 3/60 (5%) and 58/60 (96.7%) SSc patients, respectively (p < 0.001). Anti-UL57 antibodies were present in 35/40 (87.5%) MS patients and 16/17 (94.1%) NCs (SSc vs MS, MS vs NC, p = ns). Strong (50-75 AU) and very strong (75–100 AU) anti-UL57 immunoreactivity was found in 24 (41.4%) and 22 (37.9%) SSc patients, respectively (p = ns). Dilution experiments showed anti-UL57 antibody persistence in up to 1/5000. Overall, there was no difference in the frequency or the magnitude of anti-UL57 immunoreactivity between diffuse cutaneous systemic sclerosis and limited cutaneous systemic sclerosis patients (96.67 vs 96.67%; 65.45 ± 20.19 vs 64.31 ± 21.11 AU, p > 0.05) but strong anti-UL57 reactivity were more frequent in SSc compared to NCs (p = 0.007). Anti-UL57 reactivity was not inhibited by SSc-specific autoantigens. Anti-UL57 seropositivity did not correlate with demographic, clinical or immunological features of SSc. Anti-HCMV UL57 antibodies are universally present in anti-HCMV-positive patients with SSc, while those against UL44 are rarely seen. Because anti-UL57 lack disease specificity and are not involved in cross-reactive responses, their immunopathogenetic potential is to be questioned.

Keywords

Autoantibodies Immunology Infections Scleroderma 

Abbreviations

CEN

Centromere

dcSSc

Diffuse cutaneous systemic sclerosis

lcSSc

Limited cutaneous systemic sclerosis

RNA pol III

RNA polymerase III

Scl-70

Scleroderma 70

SSc

Systemic sclerosis

Notes

Acknowledgements

We thank EUROIMMUN, Germany, for providing antigens, kits and reagents.

Compliance with ethical standards

The protocol was approved by the Local Ethical Committee of the University General Hospital of Larissa (no. 1/14-1-2016).

Conflict of interest

T Scheper and W Meyer are employees of Euroimmun; all other authors do not have anything to disclose.

Source of work

Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

Financial support

ELKE (Research Committee University of Thessaly).

Part of this work was presented as a poster at the 12th Dresden Symposium on Autoantibodies, Germany, September 23–26, 2015, in a study entitled ‘Human cytomegalovirus specific antibody responses in patients with systemic sclerosis’ by C. Liaskos, E. Marou, G. Euthymiou, T. Simopoulou, C. Katsiari, W. Meyer, D.P. Bogdanos and L.I. Sakkas, as presented in Autoantigens, Autoantibodies, Autoimmunity edited by K. Conrad, E.K.L. Chan, L.E.C. Andrade, G. Steiner, G.J.M. Pruijn and Y. Shoenfeld, Pabst Science Publishers (Berlin); vol. 10—2015, p 124

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Copyright information

© International League of Associations for Rheumatology (ILAR) 2017

Authors and Affiliations

  • Emmanouela Marou
    • 1
    • 2
  • Christos Liaskos
    • 1
    • 2
  • Theodora Simopoulou
    • 1
  • Georgios Efthymiou
    • 1
    • 2
  • Efthymios Dardiotis
    • 3
  • Christina Katsiari
    • 1
  • Thomas Scheper
    • 4
  • Wolfgang Meyer
    • 4
  • Georgios Hadjigeorgiou
    • 3
  • Dimitrios P. Bogdanos
    • 1
    • 2
  • Lazaros I. Sakkas
    • 1
  1. 1.Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health SciencesUniversity of ThessalyLarissaGreece
  2. 2.Cellular Immunotherapy and Molecular Immunodiagnostics, Biomedical SectionCentre for Research and Technology-Hellas (CERTH)—Institute for Research and Technology-Thessaly (IRETETH)LarissaGreece
  3. 3.Department of Neurology, Faculty of Medicine, School of Health SciencesUniversity General Hospital of Larissa, University of ThessalyLarissaGreece
  4. 4.Institute of ImmunologyLübeckGermany

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