@article {10763, title = {Cervico-vaginal secretion cytokine profile: A non-invasive approach to study the endometrial receptivity in IVF cycles.}, journal = {Am J Reprod Immunol}, volume = {81}, year = {2019}, month = {2019 Jan}, pages = {e13064}, abstract = {

PROBLEM: Cytokines have a significant role in the process of embryo implantation, trophoblast growth, and differentiation by modulating the immune and endocrine system. The aim of this study was to investigate the profile of a large set of cytokines in the cervico-vaginal washing of women undergoing IVF, to explore the association of these proteins with a good receptive endometrium.

METHOD OF STUDY: A cohort of 155 women scheduled for IVF cycle was recruited. All patients were asymptomatic for genitourinary infections and had been screened for chlamydia, mycoplasma, and other bacterial infections. All IVF subjects were treated according to standard clinical and laboratory protocols. A panel of 48 immune factors was analyzed on cervico-vaginal washing, using magnetic bead-based multiplex immunoassays (Bio-Plex, BIO-RAD Laboratories, Milano, Italy).

RESULTS: A total of 99 patients reached embryo transfer, of which 31 had a clinical pregnancy. A pattern of four pro-inflammatory immune molecules, IL-12p40, IFN-a, MIF, and MCP3 (P~<~0.001), was found significantly up-regulated in the cervico-vaginal fluid of women with clinical pregnancy. A significantly increased expression of IL-9, Gro , and SDF-1 (P~<~0.05) was observed in the presence of endometriosis, while high levels of IL-13 and L-15 were associated with ovulatory infertility factor (P~<~0.05).

CONCLUSION: In this pilot study, we demonstrated that the expression of specific cytokines in the cervico-vaginal washing on the day of oocyte retrieval might have a positive correlation with the potential clinical pregnancy. Therefore, cervico-vaginal secretion cytokine profiling might be a new, non-invasive approach to study the endometrial receptivity in IVF management.

}, issn = {1600-0897}, doi = {10.1111/aji.13064}, author = {Zanotta, Nunzia and Monasta, Lorenzo and Skerk, Kristina and Luppi, Stefania and Martinelli, Monica and Ricci, Giuseppe and Comar, Manola} } @article {10418, title = {Cerebrospinal Fluid Cytokine Expression Profile in Multiple Sclerosis and Chronic Inflammatory Demyelinating Polyneuropathy.}, journal = {Immunol Invest}, volume = {47}, year = {2018}, month = {2018 Feb}, pages = {135-145}, abstract = {

BACKGROUND: Cerebrospinal fluid (CSF) analysis in patients with particular neurologic disorders is a powerful tool to evaluate specific central nervous system inflammatory markers for diagnostic needs, because CSF represents the specific immune micro-environment to the central nervous system.

METHODS: CSF samples from 49 patients with multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP), and non-inflammatory neurologic disorders (NIND) as controls were submitted to protein expression profiles of 47 inflammatory biomarkers by multiplex Luminex bead assay to investigate possible differences in the inflammatory process for MS and CIDP.

RESULTS: Our results showed differences in CSF cytokine levels in MS and CIDP; in particular, IL12 (p40) was significantly highly expressed in MS in comparison with CIDP and NIND, while SDF-1α and SCGF-β were significantly highly expressed in CIDP cohort when compared to MS and NIND. IL-9, IL-13, and IL-17 had higher expression levels in NIND if compared with the other groups.

CONCLUSIONS: Our study showed that, despite some common pathogenic mechanisms, central and peripheral nervous system demyelinating diseases, such as MS and CIDP, differ in some specific inflammatory soluble proteins in CSF, underlining differences in the immune response involved in those autoimmune diseases.

}, keywords = {Adult, Aged, Biomarkers, Central Nervous System, Diagnosis, Differential, Female, Hematopoietic Cell Growth Factors, Humans, Interleukin-12, Lectins, C-Type, Male, Middle Aged, Multiple Sclerosis, Peripheral Nervous System, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, Proteins}, issn = {1532-4311}, doi = {10.1080/08820139.2017.1405978}, author = {Bonin, Serena and Zanotta, Nunzia and Sartori, Arianna and Bratina, Alessio and Manganotti, Paolo and Trevisan, Giusto and Comar, Manola} } @article {10445, title = {Cytokine profiles of women with vulvodynia: Identification of a panel of pro-inflammatory molecular targets.}, journal = {Eur J Obstet Gynecol Reprod Biol}, volume = {226}, year = {2018}, month = {2018 Jul}, pages = {66-70}, abstract = {

OBJECTIVE: The vulvar pain syndrome (VPS) is a multifactorial disease severely influencing the lifestyle of affected women. Among possible etiological factors, local injury, peripheral and/or central sensitization of the nervous system, and a chronic inflammatory status have been positively associated with the development of VPS. The identification of a constitutive altered local inflammatory profile in VPS women may represent an important point in the characterization of patients{\textquoteright} phenotype as a useful marker influencing the vulvar micro-environment. The aim of this study was to investigative the possible role of the local cytokines production in women with VPS in comparison to healthy women.

STUDY DESIGN: In this study were collected vaginal swabs from 57 healthy women (HC) who never suffered from VPS and from 30 patients diagnosed with vulvodynia (VPS) by at least 3 years and currently symptomatic. All patients included in this study showed the absence of Sexually Transmitted (STD) diseases and Reproductive Tract Infection. Real-time PCR was performed to assess the genomic sequences of ST pathogens. The Luminex Bio-Plex platform was used for the analysis of a panel of 48 immune factors.

RESULTS: Eleven molecules, specifically involved in the pro-inflammatory pathway were significantly modulated in VPS patients in comparison to healthy women, suggesting a persistent inflammatory process.

CONCLUSIONS: Therefore, these inflammatory factors could be possible biological markers involved in this disease. Nevertheless, other studies are needed to consider this specific immune profile as a valid marker of the vulvodynia.

}, keywords = {Adult, Aged, Cytokines, Female, Humans, Inflammation, Middle Aged, Vaginal Smears, Vulva, Vulvodynia, Women{\textquoteright}s Health}, issn = {1872-7654}, doi = {10.1016/j.ejogrb.2018.05.035}, author = {Zanotta, Nunzia and Campisciano, Giuseppina and Scrimin, Federica and Blendi, Ura and Marcuzzi, Annalisa and Vincenti, Ezio and Crovella, Sergio and Comar, Manola} } @article {8321, title = {Candidate Soluble Immune Mediators in Young Women with High-Risk Human Papillomavirus Infection: High Expression of Chemokines Promoting Angiogenesis and Cell Proliferation.}, journal = {PLoS One}, volume = {11}, year = {2016}, month = {2016}, pages = {e0151851}, abstract = {

BACKGROUND: The causal interpretation of cervical immune response to Human Papillomavirus (HPV) infection is complex and poorly characterized mainly due to the delicate balance that exists between viral infection, increase of inflammatory cytokines and host risk factors. This study aims to explore the significance of cervical immune mediators associated to cell survival, angiogenesis and interaction with immune response, in predicting the risk to develop HPV-related intraepithelial lesions.

METHODS: A panel of 48 cytokines and growth factors were explored in a selected cohort of 168 immunocompetent women including 88 diagnosed with low (LSIL) or high (HSIL) squamous intraepithelial lesions of the cervix and 80 with normal cervical cytology (NIL). HPV genotyping was performed by Linear Array HPV test and the soluble concentration of 48 immune molecules was analyzed using the Bio-Plex platform.

RESULTS: The prevalence of single HR-HPV infection was 30\% in NIL and 100\% in LSIL and HSIL women. The expression of 13 cytokines, including interleukins IL-6, IL-3, IL-12p40, IL-12p70, IL-16, IL-18, LIF, of chemokines CCL7 (MCP-3), CXCL9 (MIG), CXCL12 (SDF-1α) and of the tropic factors VEGF, G-CSF, M-CSF were significantly associated with the presence of infection, with levels being higher in women with precancerous lesions compared to NIL HPV negative women. Only the growth factor GM-CSF was positively associated with the cytological abnormalities.

CONCLUSIONS: The ability of HR-HPV to escape from innate immune recognition and to orchestrate the production of specific inflammatory and growth factors, involved in early inflammatory response and in the cell-proliferating phase of intraepithelial damage, was documented in women before the development of cervical lesions.

}, keywords = {Adult, Cell Survival, Cervix Uteri, Chemokines, Cohort Studies, Female, Humans, Neovascularization, Pathologic, Papillomaviridae, Papillomavirus Infections}, issn = {1932-6203}, doi = {10.1371/journal.pone.0151851}, author = {Zanotta, Nunzia and Tornesello, Maria Lina and Annunziata, Clorinda and Stellato, Giovanni and Buonaguro, Franco Maria and Comar, Manola} } @article {8062, title = {Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma.}, journal = {Lung Cancer}, year = {2015}, month = {2015 Sep 25}, abstract = {

OBJECTIVES: Malignant mesothelioma (MM) is a highly aggressive tumor with poor prognosis. A major challenge is the development and application of early and highly reliable diagnostic marker(s). Serum biomarkers, such as {\textquoteright}soluble mesothelin-related proteins{\textquoteright} (SMRPs), is the most studied and frequently used in MM. However, the low sensitivity of SMRPs for early MM limits its value; therefore, additional biomarkers are required. In this study, two epigenetically regulated markers in MM (microRNA-126, miR-126, and methylated thrombomodulin promoter, Met-TM) were combined with SMRPs and evaluated as a potential strategy to detect MM at an early stage.

MATERIALS AND METHODS: A total of 188 subjects, including 45 MM patients, 99 asbestos-exposed subjects, and 44 healthy controls were prospectively enrolled, serum samples collected, and serum levels of SMRPs, miR-126 and Met-TM evaluated. Logistic regression analysis was performed to evaluate the diagnostic value of the three biomarkers. Using this approach, the performance of the {\textquoteright}3-biomarker classifier{\textquoteright} was tested by calculating the overall probability score of the MM and control samples, respectively, and the ROC curve was generated.

RESULTS AND CONCLUSION: The combination of the three biomarkers was the best predictor to differentiate MM patients from asbestos-exposed subjects and healthy controls. The accuracy and cancer specificity was confirmed in a second validation cohort and lung cancer population. We propose that the combination of the two epigenetic biomarkers with SMRPs as a diagnosis for early MM overcomes the limitations of using SMRPs alone.

}, issn = {1872-8332}, doi = {10.1016/j.lungcan.2015.09.021}, author = {Santarelli, Lory and Staffolani, Sara and Strafella, Elisabetta and Nocchi, Linda and Manzella, Nicola and Grossi, Paola and Bracci, Massimo and Pignotti, Elettra and Alleva, Renata and Borghi, Battista and Pompili, Cecilia and Sabbatini, Armando and Rubini, Corrado and Zuccatosta, Lina and Bichisecchi, Elisabetta and Valentino, Matteo and Horwood, Keith and Comar, Manola and Bovenzi, Massimo and Dong, Lan-Feng and Neuzil, Jiri and Amati, Monica and Tomasetti, Marco} } @article {1972, title = {Comparison of hybrid capture II, linear array, and a bead-based multiplex genotyping assay for detection of human papillomavirus in women with negative pap test results and atypical squamous cells of undetermined significance.}, journal = {J Clin Microbiol}, volume = {50}, year = {2012}, month = {2012 Dec}, pages = {4041-6}, abstract = {

Many methods with different levels of analytical sensitivity and clinical specificity have been developed to detect the presence of high-risk (HR) types of the human papillomavirus (HPV) in cervical samples. The Hybrid Capture II (HC-II) assay is broadly used for primary screening. In addition, several HPV genotyping assays, based on PCR methods, display higher sensitivity than the HC-II and are also used in screening programs. We evaluated the performance of three HPV DNA tests, namely, the HC-II, the Linear Array (LA) HPV genotyping assay, and an HPV type-specific E7 PCR bead-based multiplex genotyping assay (TS-MPG) that is a laboratory-developed method for the detection of HPV, in 94 women with atypical squamous cells of undetermined significance (ASC-US) and in cytological samples from 86 women with a negative Pap test. The HPV prevalence with the TS-MPG assay was increased compared to the prevalence with the LA and HC-II assays. The HPV DNA prevalence in women with ASC-US was greater with the TS-MPG assay (46.2\%) than with the LA (36.3\%) and HC-II (29.7\%) assays. The HPV DNA prevalence in the control group was greater with the TS-MPG assay (32.1\%) than with the LA assay (10.7\%). Two women with ASC-US who were HPV DNA negative by the HC-II and positive by the TS-MPG or/and LA assays had lesions that progressed to low-grade squamous intraepithelial and high-grade squamous intraepithelial lesions. This study shows that the TS-MPG assay exhibited higher analytical sensitivity than the LA and HC-II assays for the detection of HPV DNA, which reduces the potential to incorrectly identify a woman{\textquoteright}s HPV infection status.

}, keywords = {Adult, DNA, Viral, Female, Humans, Molecular Diagnostic Techniques, Papillomavirus Infections, Sensitivity and Specificity, Uterine Cervical Neoplasms, Virology}, issn = {1098-660X}, doi = {10.1128/JCM.02105-12}, author = {Comar, Manola and Iannacone, Michelle R and Casalicchio, Giorgia and McKay-Chopin, Sandrine and Tommasino, Massimo and Gheit, Tarik} }