@article {10799, title = {In vivo microbiome and associated immune markers: New insights into the pathogenesis of vaginal dysbiosis.}, journal = {Sci Rep}, volume = {8}, year = {2018}, month = {2018 02 02}, pages = {2307}, abstract = {

The microbiota fulfils a key role in the training and function of the immune system, which contributes to the symbiosis between the host and complex microbial communities. In this study, we characterized the interplay between vaginal bacteria and local immune mediators during dysbiosis in selected women of reproductive age who were grouped according to Nugent{\textquoteright}s criteria. The abundance of Gardnerella vaginalis and Bifidobacterium breve was increased in the intermediate dysbiotic status, while the presence of a plethora of non-resident bacteria characterized the group with overt vaginosis. In response to these increases, the anti-inflammatory IL1ra and pro-inflammatory IL2 increased, while the embryo trophic factors FGFβ and GMCSF decreased compared to the healthy milieu. A specific pattern, including IL1α, IL1β, IL8, MIG, MIP1α and RANTES, distinguished the intermediate group from the vaginosis group, while IL5 and IL13, which are secreted by Th2 cells, were significantly associated with the perturbation of the commensals Lactobacilli, Gardnerella and Ureaplasma. Summarizing, we postulate that although the dysbiotic condition triggers a pro-inflammatory process, the presence of a steady state level of Th2 may influence clinical manifestations. These results raise clinically relevant questions regarding the use of vaginal immunological markers as efficacious tools to monitor microbial alterations.

}, keywords = {Adult, Biomarkers, Cytokines, Dysbiosis, Female, Humans, Microbiota, Th2 Cells, Vagina}, issn = {2045-2322}, doi = {10.1038/s41598-018-20649-x}, author = {Campisciano, Giuseppina and Zanotta, Nunzia and Licastro, Danilo and De Seta, Francesco and Comar, Manola} } @article {10494, title = {Influence of vaginal lactoferrin administration on amniotic fluid cytokines and its role against inflammatory complications of pregnancy.}, journal = {J Inflamm (Lond)}, volume = {14}, year = {2017}, month = {2017}, pages = {5}, abstract = {

BACKGROUND: An altered amniotic cytokine profile has been reported in inflammatory pregnancy complications with a leading role for IL-6, a marker of the foetal systemic inflammatory response. Up to this date there is no exhaustive information neither on the foetal cytokine balance nor on the best method for its modulation. We aimed to evaluate the influence of vaginal lactoferrin administration on amniotic fluid concentration of 47 cytokines, chemokines and growth factors.

METHODS: Sixty women undergoing genetic amniocentesis were enrolled in an open-label clinical trial. 300~mg of vaginal lactoferrin (Florence, Italy) were randomly administered to obtain 3 groups: A, 20 untreated patients; B and C (20 patients in each) respectively treated 4 and 12~h before amniocentesis. Cytokines, chemokines and growth factors concentrations were quantified by a magnetic bead Luminex multiplex immunoassays panel technology. Data analysis was performed with the software Stata (v. 13.1) and GraphPad Prism (v. 5). Group comparisons were performed using Kruskal-Wallis followed by Mann-Whitney U tests, with Bonferroni correction for multiple comparisons. A < 0.05 was considered significant.

RESULTS: Among the 47 tested mediators, 24 (51.06\%) were influenced by lactoferrin. 11 (23.4\%), showed a highly significant difference (p <0.001); among these IL-9, IL-15, IFN-γ, IP-10, TNF-α, IL-1α and MCP-3 underwent a down-regulation, while IL-17 and FGF-basic, G-CSF, GM-CSF an up-regulation. Difference between group C and both B and A was small for IL-15, IP-10, IL-1α, MCP-3, while it was negligible for IL-9, IFN-γ and TNF-α. IL-17 and the 3 growth factors were strongly enhanced in B and C groups. IL-17, FGF-basic and GM-CSF showed increasing concentrations in both B and C groups, while G-CSF resulted up-regulated only in group C. Significance was intermediate ( < 0.01) for the down regulated IL-2RA, IL-12p40 and IFNα2 (6.38\%) while it was small for 10 mediators (21.27\%) 7 of which (IL-2, IL-4, eotaxin, PDGF-BB, RANTES, IL-18 and MIF) down-regulated and 3 (MCP-1, IL-3, and SDF-1α) up-regulated.

CONCLUSION: Lactoferrin down-regulates 17 pro-inflammatory amniotic mediators while up-regulating 7 anti-inflammatory amniotic mediators, 5 of which definitively belonging to an anti-inflammatory profile. These findings open to clinical investigation on its use against inflammatory complications of pregnancy.

}, issn = {1476-9255}, doi = {10.1186/s12950-017-0152-9}, author = {Maritati, Martina and Comar, Manola and Zanotta, Nunzia and Seraceni, Silva and Trentini, Alessandro and Corazza, Fabrizio and Vesce, Fortunato and Contini, Carlo} } @article {7772, title = {Immunologic evidence of a strong association between non-Hodgkin lymphoma and simian virus 40.}, journal = {Cancer}, volume = {121}, year = {2015}, month = {2015 Aug 1}, pages = {2618-26}, 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 = 89] and NHL2 [n = 61]) along with controls represented by oncologic patients affected by breast cancer (BC; n = 78) and undifferentiated nasopharyngeal carcinoma (UNPC; n = 64) and 3 different cohorts of healthy subjects (HSs; HS1 [n = 130], HS2 [n = 83], and HS3 [n = 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.

CONCLUSIONS: Our data indicate a strong association between NHL and SV40 and thus a need for innovative therapeutic approaches for this hematologic malignancy.

}, keywords = {Adult, Aged, Antibodies, Viral, Capsid Proteins, Enzyme-Linked Immunosorbent Assay, Female, Humans, Lymphoma, Non-Hodgkin, Male, Middle Aged, Polyomavirus Infections, Seroepidemiologic Studies, Simian virus 40, Tumor Virus Infections}, issn = {1097-0142}, doi = {10.1002/cncr.29404}, author = {Tognon, Mauro and Luppi, Mario and Corallini, Alfredo and Taronna, Angelo and Barozzi, Patrizia and Rotondo, John Charles and Comar, Manola and Casali, Maria Vittoria and Bovenzi, Massimo and D{\textquoteright}Agostino, Antonio and Vinante, Fabrizio and Rigo, Antonella and Ferrarini, Isacco and Barbanti-Brodano, Giuseppe and Martini, Fernanda and Mazzoni, Elisa} } @article {3503, title = {In vivo detection of polyomaviruses JCV and SV40 in mesenchymal stem cells from human umbilical cords.}, journal = {Pediatr Blood Cancer}, volume = {61}, year = {2014}, month = {2014 Aug}, pages = {1347-9}, abstract = {

BACKGROUND: Multipotent stromal cells are present in the Wharton{\textquoteright}s jelly matrix (WJSC) of the umbilical cord and can be used as an allogeneic source of cells to treat immunological disorders. Recently it was demonstrated that adult bone marrow (BM)-derived mesenchimal stromal cells (MSC) are susceptible to infection with viruses showing potential oncogenic properties, such as the polyomavirus JC (JCV). The aim of this study was to investigate the presence of human polyomaviruses (JCV, BK Virus-BKV, SV40, and Merkel cell polyomavirus-MCPyV) in WJSC, and explore the risk of infection.

PROCEDURE: MSC samples from 35 umbilical cords were investigated by quantitative Real Time PCRs for the presence of DNA sequences of JCV, BKV, SV40, and MCPyV.

RESULTS: JCV DNA was detected in 1/35 (2.8\%) of MSC samples, while SV40 DNA was found in 3/35 (8.6\%) of the examined samples. None of the samples showed sequences of BKV and MCPyV.

CONCLUSIONS: The present study demonstrates the in vivo ability of polyomaviruses to infect WJSC. Since the therapeutic approach with the WJSC has high potentiality and a more intensive use can be easily hypothesized, the need to develop consensus guidelines to detect rare viral infections in MSC is pressing.

}, keywords = {DNA, Viral, Female, Fetal Blood, Humans, JC Virus, Male, Mesenchymal Stromal Cells, Polyomavirus Infections, Simian virus 40, Tumor Virus Infections}, issn = {1545-5017}, doi = {10.1002/pbc.24943}, author = {Comar, Manola and Delbue, Serena and Zanotta, Nunzia and Valencic, Erica and Piscianz, Elisa and Del Savio, Rossella and Tesser, Alessandra and Tommasini, Alberto and Ferrante, Pasquale} } @article {3589, title = {Increased levels of C-C chemokine RANTES in asbestos exposed workers and in malignant mesothelioma patients from an hyperendemic area.}, journal = {PLoS One}, volume = {9}, year = {2014}, month = {2014}, pages = {e104848}, abstract = {

BACKGROUND: Asbestos-induced mesothelial inflammatory processes are thought to be the basic mechanisms underlying Malignant Mesothelioma (MM) development. Detection of MM often occurs at late stage due to the long and unpredictable latent period and the low incidence in asbestos exposed individuals. The aim of this study was to investigate early immunological biomarkers to characterize the prognostic profile of a possible asbestos-induced disease, in subjects from a MM hyperendemic area.

METHODS: The Luminex Multiplex Panel Technology was used for the simultaneous measurement of serum levels of a large panel of 47 analytes, including cytokines and growth factors, from workers previously exposed to asbestos (Asb-workers), asbestos-induced MM patients and healthy subjects. In addition, to explore the influence on serum cytokines profile exerted by SV40 infection, a cofactor in MM development, a quantitative real time PCR was performed for sequences detection in the N-terminal and intronic regions of the SV40 Tag gene. Statistical analysis was done by means of the Mann-Whitney test and the Kruskall-Wallis test for variance analysis.

RESULTS: A variety of 25 cytokines linked to pulmonary inflammation and tumor development were found significantly associated with Asb-workers and MM patients compared with healthy controls. A specific pattern of cytokines were found highly expressed in Asb-workers: IFN-alpha (p<0.05), EOTAXIN (p<0.01), RANTES (p<0.001), and in MM patients: IL-12(p40), IL-3, IL-1 alpha, MCP-3, beta-NGF, TNF-beta, RANTES (p<0.001). Notably, the chemokine RANTES measured the highest serum level showing an increased gradient of concentration from healthy subjects to Asb-workers and MM patients (p<0.001), independently of SV40 infection.

CONCLUSION: This study shows that, in subjects from an hyperendemic area for MM, the C-C chemokine RANTES is associated with the exposure to asbestos fibres. If validated in larger samples, this factor could have the potential to be a critical biomarker for MM prognosis as recently reported for breast tumor.

}, keywords = {Aged, Aged, 80 and over, Asbestos, Biomarkers, Tumor, Case-Control Studies, Chemokine CCL5, Cytokines, Endemic Diseases, Gene Expression, Gene Expression Profiling, Humans, Lung Neoplasms, Mesothelioma, Middle Aged, Occupational Exposure, Simian virus 40, Viral Proteins}, issn = {1932-6203}, doi = {10.1371/journal.pone.0104848}, author = {Comar, Manola and Zanotta, Nunzia and Bonotti, Alessandra and Tognon, Mauro and Negro, Corrado and Cristaudo, Alfonso and Bovenzi, Massimo} }