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Cancer Immunology, Immunotherapy

, Volume 66, Issue 9, pp 1189–1198 | Cite as

High prevalence of antibodies reacting to mimotopes of Simian virus 40 large T antigen, the oncoprotein, in serum samples of patients affected by non-Hodgkin lymphoma

  • Elisa Mazzoni
  • Silvia Pietrobon
  • Miriam Bilancia
  • Fabrizio Vinante
  • Antonella Rigo
  • Isacco Ferrarini
  • Antonio D’Agostino
  • Maria Vittoria Casali
  • Fernanda Martini
  • Mauro TognonEmail author
Original Article

Abstract

A new immunological investigation was carried out to study the association between non-Hodgkin lymphoma and Simian virus 40 (SV40). To this end, a new indirect ELISA was employed with two mimotopes from SV40 large T antigen (Tag), the viral oncoprotein, to analyse for specific reactions to antibodies in sera from non-Hodgkin lymphoma patients and controls, represented by healthy subjects (HS) and breast carcinoma (BC) patients. This study allowed us to assay a new sera collection from non-Hodgkin lymphoma patients (NHL, n = 254). To verify the association between NHL and SV40 Tag, two totally independent cohorts were analysed: NHL1 n = 150 and NHL2 n = 104. The epidemiological survey included sera from HS1, n = 150; HS2, n = 104 and BC, n = 78. This new indirect ELISA revealed that antibodies against SV40 Tag mimotopes are detectable in NHL1 and NHL2 sera with a prevalence of 37 and 36%, respectively. The prevalence of SV40-antibodies detected in both NHL1 and NHL2 cohorts differs statistically from controls, at 19% for HS1 (p < 0.01), HS2 (p < 0.05) and BC patients (p < 0.05). This study, carried out with an immunological assay with specific Tag oncoprotein mimotopes of Simian virus 40, reports the presence of IgG antibodies against the large Tumour antigen in non-Hodgkin lymphomas for the first time. Our immunological data with two independent NHL cohorts show a statistically significant association between Simian virus 40 Tag and non-Hodgkin lymphoma. These results suggest that SV40-positive non-Hodgkin lymphomas could be treated differently from those tested SV40-negative.

Keywords

NHL SV40 Infection T antigen Mimotope Antibody 

Abbreviations

a.a.

Amino acid

ABTS

2,2′-Azino-bis 3-ethylbenzthiazoline-6-sulfonic acid

BC

Breast cancer

BKPyV

BK polyomavirus

CI

Confidence interval

ELISA

Enzyme-linked immunosorbent assay

hNPS

Human neuro-peptide S

HS

Healthy subjects

IgG

Immunoglobulin G

JCPyV

JC polyomavirus

MCPyV

Merkel cell polyomavirus

NHL

Non-Hodgkin lymphoma

OD

Optical density

SV40

Simian virus 40

Tag

Large T antigen

tag

Small t antigen

VLP

Virus-like particle

VP

Viral protein

WHO/IARC

World Health Organization/International Agency for Research on Cancer

y

Year

yrs

Years

Notes

Acknowledgements

We would like to thank Dr. Eugene O. Major, the Laboratory of Molecular Medicine and Neuroscience, The National Institute of Neurological Disorders and Strokes, Bethesda, MD, for the hyperimmune serum against JCPyV and Prof. Janet S. Butel, Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX, for the hyperimmune serum against SV40 Tag. We wish to thank Ms. Georgia Emma Gili for revising the English text of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors have no financial conflicts of interest.

Funding

This research was supported by Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research, AIRC, Milan); Associazione Sammarinese lotta contro le leucemie e le ematopatie maligne (Association Sammarinese fight against leukaemia and haematologic malignancies, ASLEM, Republic of San Marino); Fondazione Buzzi UNICEM Onlus, (non-profit Buzzi Unione Cementieri Foundation, Casale Monferrato); Fondazione CARICE, Cento (Foundation of the Saving Bank of Cento); University of Ferrara, Ferrara, Italy.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Elisa Mazzoni
    • 1
  • Silvia Pietrobon
    • 1
  • Miriam Bilancia
    • 1
  • Fabrizio Vinante
    • 2
  • Antonella Rigo
    • 2
  • Isacco Ferrarini
    • 2
  • Antonio D’Agostino
    • 3
  • Maria Vittoria Casali
    • 4
  • Fernanda Martini
    • 1
  • Mauro Tognon
    • 1
    Email author
  1. 1.Section of Pathology, Oncology and Experimental Biology, Department of Morphology, Surgery and Experimental Medicine, School of MedicineUniversity of FerraraFerraraItaly
  2. 2.Section of Haematology, Department of Medicine, School of MedicineUniversity of VeronaVeronaItaly
  3. 3.Department of SurgeryUniversity of VeronaVeronaItaly
  4. 4.Hospital Headquarter DepartmentState Hospital, Institute for Social SecuritySan MarinoRepublic of San Marino

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