Immunologic evidence of a strong association between non‐Hodgkin lymphoma and simian virus 40

Abstract

BACKGROUND: Non-Hodgkin lymphoma (NHL), the most common cancer of the lymphatic system, is of unknown etiology. The identification of etiologic factors in the onset of NHL is a key event that could facilitate the prevention and cure of this malignancy. Simian virus 40 (SV40) has been considered an oncogenic agent in the onset/progression of NHL. METHODS: In this study, an indirect enzyme-linked immunosorbent assay with 2 synthetic peptides that mimic SV40 antigens of viral capsid proteins 1 to 3 was employed to detect specific antibodies against SV40. Serum samples were taken from 2 distinct cohorts of NHL-affected patients (NHL1 [n 5 89] and NHL2 [n 5 61]) along with controls represented by oncologic patients affected by breast cancer (BC; n 5 78) and undifferentiated nasopharyngeal carcinoma (UNPC; n 5 64) and 3 different cohorts of healthy subjects (HSs; HS1 [n 5 130], HS2 [n 5 83], and HS3 [n 5 87]). RESULTS: Immunologic data indicated that in serum samples from NHL patients, antibodies against SV40 mimotopes were detectable with a prevalence of 40% in NHL1 patients and with a prevalence of 43% in NHL2 patients. In HSs of the same median age as NHL patients, the prevalence was 16% for the HS1 group (57 years) and 14% for the HS2 group (65 years). The difference was statistically significant (P <.0001 and P <.001). Interestingly, the difference between NHL1/NHL2 patients and BC patients (40%/43% vs 15%, P <.001) and between NHL1/NHL2 patients and UNPC patients (40%/43% vs 25%, P <.05) was significant. CON-CLUSIONS: Our data indicate a strong association between NHL and SV40 and thus a need for innovative therapeutic approaches for this hematologic malignancy.

Specific Antibodies Reacting with SV40 Large T Antigen Mimotopes in Serum Samples of Healthy Subjects

“…Independent analyses reported the detection of SV40 DNA sequences and viral neutralizing and IgG antibodies in healthy subjects, including in children, adolescents, adults, elderly individuals, and pregnant women [ 1 – 6 ]. Similar investigations detected SV40 markers in patients affected by cancers of different histotypes [ 7 – 14 ].…”

“…We have recently contributed to this goal by developing an innovative indirect enzyme-linked immunosorbent assay (ELISA) with synthetic peptides, which mimic antigens of the viral capsid proteins 1, 2 and 3 (VPs 1–3). This indirect ELISA is specific for the detection of SV40 antibodies in human sera and does not react with different genetic variants of the closely related human polyomaviruses BKPyV and JCPyV or with other less-homologous human polyomaviruses [ 1 – 4 , 8 , 10 – 12 , 14 ]. Immunologic data obtained with this assay indicated that the prevalence of SV40 serum IgG antibodies in healthy adults is approximately 18%, whereas antibody prevalence is significantly higher (2–3 times) in patients affected by SV40-associated tumors [ 1 – 4 , 8 , 10 – 12 ].…”

New developments in the pathology of malignant lymphoma: a review of literature published from January 2015 to April 2015

“…There are other microorganisms involved in lymphomas like the Epstein-Barr virus (EBV), hepatitis C and Helicobacter pylori (amongst others). According to Tognon et al [ 13 ], we need to add simian virus 40 (SV40) to the list. In serum samples from NHL-affected patients ( n = 150) along with controls represented by patients with other cancers ( n = 142) and healthy subjects ( n = 300), they found antibodies against SV40 in about 40 % of the NHL patients, 20 % in other cancer patients and 15 % in healthy individuals.…”

New developments in the pathology of malignant lymphoma. A review of the literature published from January 2014–April 2014

“…According to Tognon et al [13], we need to add simian virus 40 (SV40) to the list. In serum samples from NHL-affected patients (n=150) along with controls represented by patients with other cancers (n= 142) and healthy subjects (n=300), they found antibodies against SV40 in about 40 % of the NHL patients, 20 % in other cancer patients and 15 % in healthy individuals.…”