@article {10576, title = {Natalizumab treatment of multiple sclerosis: new insights.}, journal = {Immunotherapy}, volume = {9}, year = {2017}, month = {2017 01}, pages = {157-171}, abstract = {

Natalizumab is a monoclonal antibody directed against the α4 chain of the very late activating antigen 4 and α4β7 integrins, present on the leukocytes surface, used as monotherapy for the treatment of relapsing-remitting multiple sclerosis. It substantially reduces relapse rate and the accumulation of disability, but its use is associated with a very adverse event, that is the development of progressive multifocal leukoencephalopathy, a fatal demyelinating disease of the CNS, due to the lytic replication of the human polyomavirus JC. The main focus of the review is to describe the newest insights on natalizumab, its current use in the clinical practice, the natalizumab-treated patients{\textquoteright} management and the risk stratification related to the progressive multifocal leukoencephalopathy development.

}, keywords = {Animals, Drug-Related Side Effects and Adverse Reactions, Humans, Immunotherapy, Integrin alpha Chains, Integrin alpha4, Integrin beta Chains, JC Virus, Leukoencephalopathy, Progressive Multifocal, Multiple Sclerosis, Relapsing-Remitting, Natalizumab, Risk, Virus Activation, Virus Replication}, issn = {1750-7448}, doi = {10.2217/imt-2016-0113}, author = {Delbue, Serena and Comar, Manola and Ferrante, Pasquale} } @article {3609, title = {Neutralizing and IgG antibodies against simian virus 40 in healthy pregnant women in Italy.}, journal = {PLoS One}, volume = {9}, year = {2014}, month = {2014}, pages = {e110700}, abstract = {

OBJECTIVE: Polyomavirus simian virus 40 (SV40) sequences have been detected in various human specimens and SV40 antibodies have been found in human sera from both healthy individuals and cancer patients. This study analyzed serum samples from healthy pregnant women as well as cord blood samples to determine the prevalence of SV40 antibodies in pregnancy.

METHODS: Serum samples were collected at the time of delivery from two groups of pregnant women as well as cord bloods from one group. The women were born between 1967 and 1993. Samples were assayed by two different serological methods, one group by neutralization of viral infectivity and the other by indirect ELISA employing specific SV40 mimotopes as antigens. Viral DNA assays by real-time polymerase chain reaction were carried out on blood samples.

RESULTS: Neutralization and ELISA tests indicated that the pregnant women were SV40 antibody-positive with overall prevalences of 10.6\% (13/123) and 12.7\% (14/110), respectively. SV40 neutralizing antibodies were detected in a low number of cord blood samples. Antibody titers were generally low. No viral DNA was detected in either maternal or cord bloods.

CONCLUSIONS: SV40-specific serum antibodies were detected in pregnant women at the time of delivery and in cord bloods. There was no evidence of transplacental transmission of SV40. These data indicate that SV40 is circulating at a low prevalence in the northern Italian population long after the use of contaminated vaccines.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0110700}, author = {Comar, Manola and Wong, Connie and Tognon, Mauro and Butel, Janet S} } @article {3483, title = {No evidence of Polyomavirus and EBV infections in Italian patients with mixed cryoglobulinemia infected chronically with HCV.}, journal = {J Med Virol}, volume = {86}, year = {2014}, month = {2014 Apr}, pages = {666-71}, abstract = {

Mixed cryoglobulinemia is a lymphoproliferative disorder associated with hepatitis C virus (HCV). In patients chronically affected by HCV the prevalence of mixed cryoglobulinemia is variable ranging from 0\% to 56\%. To verify whether polyomaviruses (PyV) play a role in this disorder a total of 222 blood samples from 63 HCV chronic patients, 43 with mixed cryoglobulinemia, 59 chronic lymphocytic leukemia, 50 polytransfused patients, and 50 blood donors were evaluated for Merkel (MCPyV), BKV, JCV, and SV40. EBV was additionally included in the analysis since association with this disorder has been reported. Mixed cryoglobulinemia patients infected chronically with HCV resulted negative for both PyV and EBV. MCPyV was found in 1 subject with Merkel Cell Carcinoma, in 10\% of polytransfused and in 10\% of blood donors while EBV was detected in 22\% of polytransfused, 10\% of B-cell lymphatic leukemia patients and 4\% of blood donors (P < 0.01). Taken together, the absence of PyV and EBV in HCV-mixed cryoglobulinemia patients seems to exclude a direct involvement of these viruses in the pathogenesis of this disease while the presence of MCPyV in healthy individuals, at the same rate as in polytransfused patients, may reinforce data on a minimal role of this virus in other human pathologies.

}, keywords = {Adult, Base Sequence, Cryoglobulinemia, DNA, Viral, Epstein-Barr Virus Infections, Female, Hepacivirus, Hepatitis C, Chronic, Herpesvirus 4, Human, Humans, Italy, Leukemia, B-Cell, Male, Middle Aged, Polyomavirus, Polyomavirus Infections, Sequence Analysis, DNA, Vaginal Smears, Young Adult}, issn = {1096-9071}, doi = {10.1002/jmv.23867}, author = {Comar, Manola and Zanotta, Nunzia and Del Savio, Rossella and Vascotto, Fulvia and Calabrese, Nadia and Zorat, Francesca and Pozzato, Gabriele} } @article {1971, title = {NLRP1 polymorphisms in patients with asbestos-associated mesothelioma.}, journal = {Infect Agent Cancer}, volume = {7}, year = {2012}, month = {2012}, pages = {25}, abstract = {

UNLABELLED:

BACKGROUND: An increasing incidence of malignant mesothelioma (MM) cases in patients with low levels of asbestos exposure suggests the interference of alternative cofactors. SV40 infection was detected, as co-morbidity factor, only in 22\% of asbestos-MM patients from a North-Eastern Italy area. An additional mechanism of injury related to asbestos exposure in MM development has been recently associated to inflammatory responses, principally driven by interleukin (IL)-1 beta ({\ss}) activated within the inflammasome complex.NLRP3 inflammosome has been described as the intracellular sensor for asbestos able to induce inflammasome activation and IL-1{\ss} secretion while NLRP1 is expressed in lung epithelial cells and alveolar macrophages and contributes to the immune response and to survival/apoptosis balance. This study proposes to evaluate the impact of known NLRP3 and NLRP1 polymorphisms in the individual susceptibility to asbestos-induced mesothelioma in subjects from a hyperendemic area for MM.

METHODS: 134 Italian patients with diagnosis of mesothelioma due (MMAE, n=69) or not (MMAF, n=65) to asbestos, 256 healthy Italian blood donors and 101 Italian healthy subjects exposed to asbestos (HCAE) were genotyped for NLRP1 (rs2670660 and rs12150220) and NLRP3 (rs35829419 and rs10754558) polymorphisms.

RESULTS: While NLRP3 SNPs were not associated to mesothelioma, the NLRP1 rs12150220 allele T was significantly more frequent in MMAE (0.55) than in HCAE (0.41) (p=0.011; OR=1.79) suggesting a predisponent effect of this allele on the development of mesothelioma. This effect was amplified when the NLRP1 rs2670660 allele was combined with the NLRP1 rs12150220 allele (p=0.004; OR=0.52).

CONCLUSION: Although NLRP3 SNPs was not involved in mesothelioma predisposition, these data proposed NLRP1 as a novel factor possibly involved in the development of mesothelioma.

}, issn = {1750-9378}, doi = {10.1186/1750-9378-7-25}, author = {Girardelli, Martina and Maestri, Iva and Rinaldi, Rosa R and Tognon, Mauro and Boldorini, Renzo and Bovenzi, Massimo and Crovella, Sergio and Comar, Manola} }