Heavy flavor physics with CMS

Different recent results from CMS Collaboration on Quarkonia Physics and Heavy Quarks production are presented. All these results have been obtained analyizing the data of $pp$ collisions at sqrt{s}=7 TeV provided by the LHC and collected by the CMS detector in the year 2010. The measurements of B-mesons, charmed mesons and open beauty production cross--sections are illustrated, together with the analysis techniques and the estimation of the systematics uncertainties, and compared with the predictions of the available theoretical models. A recent result from CDF on the Upsilon polarization is also reported.Comment: FPCP 2011 Conference Report, 23 pages, 13 figure

Measurements of Inclusive b-quark Production at 7 TeV with the CMS Experiment

Measurements performed by the CMS experiment of the cross section for inclusive b-quark production in proton-proton collisions at sqrt(s) = 7 TeV are presented. The measurements are based on different methods, such as inclusive jet measurements with secondary vertex tagging or selecting a sample of events containing jets and at least one muon, where the transverse momentum of the muon with respect to the closest jet axis discriminates b events from the background. The results are compared with predictions based on perturbative QCD calculations at leading and next-to-leading order.Comment: 9 pages, 4 figures, conference proceeding

Osteoporosis in rheumatoid arthritis: role of the vitamin D/parathyroid hormone system

AbstractOsteoporosis is a well-established extra-articular feature of rheumatoid arthritis (RA). Systemic inflammation seems to play a crucial role in causing an alteration of multiple homeostatic systems implied in bone health, such as the RANK/RANKL/Osteoprotegerin and Wnt/β catenin pathways; several other causal factors have been called into question, including the chronic use of corticosteroids. Since vitamin D exerts important immune-regulatory roles, it has been claimed that derangement of the vitamin D/parathyroid hormone (PTH) system, a well-known determinant of bone health, may play a pathogenic role in autoimmunity; animal models and clinical data support this hypothesis. Furthermore, RA patients seem to be relatively refractory to vitamin D-induced PTH suppression. Therefore, the link between RA and osteoporosis might in part be due to alterations in the vitamin D/PTH system. A better understanding of the pathophysiology of this system may be crucial to prevent and cure osteoporosis in patients with inflammatory/autoimmune diseases. A major clinical correlate of the strict cooperation and interdependence between vitamin D and PTH is that correction of the vitamin D deficiency, at least in autoimmune diseases, should be targeted to PTH suppression

Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases

Vitamin D is a pleiotropic secosteroid yielding multiple actions in human physiology. Besides the canonical regulatory activity on bone metabolism, several non-classical actions have been described and the ability of vitamin D to partake in the regulation of the immune system is particularly interesting, though far stronger and convincing evidence has been collected in in vitro as compared to in vivo studies. Whether vitamin D is able to regulate at physiological concentrations the human immune system remains unproven to date. Consequently, it is not established if vitamin D status is a factor involved in the pathogenesis of immune-mediated diseases and if cholecalciferol supplementation acts as an adjuvant for autoimmune diseases. The development of autoimmunity is a heterogeneous process, which may involve different organs and systems with a wide range of clinical implications. In the present paper, we reviewed the current evidences regarding vitamin D role in the pathogenesis and management of different autoimmune diseases

Is cholecalciferol a potential disease modifying anti-rheumatic drug for the management of rheumatoid arthritis?

Vitamin D is a pleiotropic molecule with a well-characterised immunomodulatory activity in vitro; however, its potential clinical application in autoimmune conditions has yet to be clarified. Several authors have investigated the use of vitamin D as a disease-modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA), obtaining divergent conclusions. This systematic review summarises and critically analyses the findings of papers assessing the impact of vitamin D supplementation on pain relief, disease activity, functional status and flare rate. We conclude that the correction of hypovitaminosis D may have a beneficial effect on pain perception; moreover, the achievement of an adequate plasma vitamin D concentration obtained with high-dose regimens might evoke immunomodulatory activities of vitamin D and favourably impact on disease control. Nevertheless, the current evidence is still not strong enough to support the use of cholecalciferol as a DMARD in RA, and further studies are required to clarify this issue

Exploring serum and CSF Calcitonin Gene Related Peptide levels: A promising biomarker in multiple sclerosis?

Introduction: Calcitonin Gene Related Peptide (CGRP) is a neuropeptide ubiquitous in the peripheral and central nervous system, mostly known for the role in vasodilation and pain signal transmission during migraine attacks. Recent studies have been unraveling its immunomodulatory properties, including its possible role in multiple sclerosis (MS) pathophysiology, however there is no conclusive evidence on whether it plays a pro or anti-inflammatory role. Objectives/Aims: To evaluate soluble CGRP levels at MS diagnosis, in cerebrospinal fluid (CSF) and serum, and evaluate associations with progression and short-term disease severity. Methods: We enrolled for a retrospective cohort study 59 patients (39 females, mean age at diagnosis 38.79 years ± standard deviation or SD 9.89) with Radiological Isolated Syndrome (RIS), Clinical Isolated Syndrome (CIS) and Relapsing-Remitting (RR) MS. During the diagnostic work-up were collected clinic-demographic data, serum and CSF. Patients were followed with clinical visits in which clinical data were collected.*** CGRP levels were determined through an ELISA commercial kit (MyBioSource Inc, MBS267126, San Diego, CA, USA). None had a history of migraine attack at diagnosis. Statistical analyses were conducted with STATA software to determine Mann–Whitney, Kruskal-Wallis test and Spearman’s rank correlation coefficient significance. Results: CGRP levels were significantly higher in MS patients if compared to healthy controls published by Papiri et Al. (PMID: 37013432) and Han et Al. (PMID: 35204700). Mean values resulted 73.10 pg/ml in serum (±9.42 vs 29.50 ± 8.91, p<0.05 t-test) and 64.01 in CSF (± 10.39 vs 52.05 ± 5.70, p<0.05 t-test). CGRP levels did not relate to clinical variables at diagnosis: age, gender, Expanded Disability Status Scale (EDSS), number of T2, gadolinium enhancing and spinal cord lesions. However, there was a positive correlation between serum CGRP and the Multiple Sclerosis Severity Score (MSSS) at the last follow up (r2 = 0.27, p<0.05 Spearman’s rank correlation). Conclusion: We observed an increased CGRP level in the CSF and serum of MS patients at diagnosis. Our findings suggest its potential use as a biomarker to identify cases with poor prognosis, indicating a pro-inflammatory effect of this neuropeptide

Gas6/TAM system: potential prognostic biomarker for Multiple Sclerosis

Introduction: The protein growth arrest specific 6 (Gas6) and its tyrosine kinase receptors Tyro-3, Axl, Mer (TAMs) are ubiquitous proteins involved in regulation of inflammation and apoptotic body clearance. Gas6 and TAMs have been associated with neuronal remyelination and stimulation of oligodendrocyte survival. However, few data are available on their role in multiple sclerosis (MS). Objectives/Aims: Objectives/Aims: In this study we evaluated if soluble levels of these molecules, determined at MS diagnosis in cerebrospinal fluid (CSF) and serum, correlated with progression with short-term disease severity. Methods: Methods: We conducted a retrospective cohort study enrolling 64 patients with different forms of MS, the Radiological Isolated Syndrome (RIS), the Clinical Isolated Syndrome (CIS) and Relapsing-Remitting (RR). At diagnosis, we collected serum, CSF, and clinical-radiological data: lesion load, spinal cord, and gadolinium-enhancing (Gad+) lesions, and expanded disability status score (EDSS). During the last clinical follow-up EDSS, MS severity score (MSSS) and Age-Related MS severity (ARMSS) were assessed. Gas6 and TAMs were determined by ELISA kit (R&D Systems), while neurofilaments (NFLs) levels, for neuronal damage assessment, by SimplePlexTM fluorescence-based immunoassay. Statistical analyses were conducted with STATA software to determine Mann–Whitney, Kruskal-Wallis test and Spearman’s rank correlation coefficient significance. Results: Results: At diagnosis, RIS and CIS showed higher values of sMer and sTyro-3, compared to RRMS (p = 0.007 and p = 0.018). Serum sAxl was higher in patients untreated or first-line disease modifying treatments (DMTs) versus patients with high-efficacy DMTs (p = 0.04). Moreover, serum Axl was associated with EDSS ≤ 3 at diagnosis (p = 0.037) and EDSS progression in patients with EDSS ≤ 3 (p = 0.017). Similarly, high levels of Gas6 in CSF were associated with EDSS ≤ 3 at diagnosis (p = 0.04), and high levels of Gas6 in serum to a lower MSSS (r2 = -0.32 and p = 0.01). Results significances were confirmed by multivariate analyses. In our cohort, serum and CSF NFLs levels were confirmed as markers of disability in EDSS (p = 0.005 and p = 0.002) and MSSS (r2 = 0.27 and p =0.03; r2 = 0.39 and p = 0.001). Conclusion: Conclusion: Taken together, our results suggest that Gas6 and its receptors, particularly Axl, might have a neuroprotective role and prognostic potential in MS. Disclosures: Disclosures: Nothing to disclos

SARS-CoV-2 infection risk is higher in vaccinated patients with inflammatory autoimmune diseases or liver transplantation treated with mycophenolate due to an impaired antiviral immune response: results of the extended follow up of the RIVALSA prospective cohort

BackgroundA relevant proportion of immunocompromised patients did not reach a detectable seroconversion after a full primary vaccination cycle against SARS-CoV-2. The effect of different immunosuppressants and the potential risks for SARS-CoV-2 infection in these subjects is largely unknown.MethodsPatients from the Rivalsa prospective, observational cohort study with planned anti SARS-CoV-2 third dose mRNA vaccination between October and December 2021 were asked to participate to this follow-up study. Patients were asked about eventual confirmed positivity to SARS-CoV-2 infection within 6 months from the third dose and to undergo a blood draw to evaluate seroconversion status after the additional vaccine shot.Results19 out of 114 patients taking part in the survey developed a confirmed SARS-CoV-2 infection; we identified mycophenolate treatment as an independent predictor of an increased risk of infection even after the third vaccine dose (OR: 5.20, 95% CI: 1.70-20.00, p=0.0053). This result is in agreement with the in vitro evidence that MMF impairs both B and T lymphocytes driven immune responses (reduction both in memory B cells producing anti-spike antibodies and in proliferating CD4+ and CD8+ T cells).ConclusionsImmunocompromised patients need an additional vaccine administration to reach a detectable seroconversion, thus fostering a more personalized approach to their clinical management. Moreover, patients undergoing mycophenolate treatment show a specific increased infection risk, with respect to other immunosuppressants thus supporting a closer monitoring of their health status