CD69 molecule in human neutrophils: its expression and role in signal trasducing mechanisms

The CD69 glycoprotein is an early activation antigen of T and B lymphocytes and it is constitutively expressed on thymocytes and platelets. Here we report its presence on neutrophils and on bone marrow-derived myeloid precursors. Indeed, promyelocytic cells are CD69+ on the cell membrane, while in resting neutrophils this molecule is located inside the cell. However, intracellular CD69 molecules are rapidly mobilized to the cell surface upon activation by PMA or fMLP. This translocation is independent on a new protein synthesis, as it is not inhibited by cycloheximide; furthermore, CD69 molecules are likely stored in a trans-Golgi structure since their expression is not affected by brefeldin A, a drug that blocks molecular trafficking from ER to Golgi vesicles. Immunoprecipitation of CD69 molecules either from activated neutrophils or from bone marrow cells showed that this protein has the same molecular size (28-34 kDa) as observed in platelets, T and B lymphocytes, and thymocytes. This similarity is reflected also in the functional role played by this molecule: in neutrophils as well as in lymphocytes and platelets, CD69 stimulation induced Ca2+ influx through cellular membrane; furthermore, the perturbation of the CD69 antigen on PMA-activated neutrophils enhances the lysozyme release, suggesting a role of this molecule in the regulation of granule exocytosis, probably through a Ca(2+)-dependent mechanism

Adalimumab trough serum levels and anti-adalimumab antibodies in the long-term clinical outcome of patients with Crohn\u2019s disease.

OBJECTIVE: Few data are available on the relevance of adalimumab (ADA) trough serum levels and anti-ADA antibodies (AAA) during long-term follow-up of patients with Crohn's Disease (CD), and their association with disease outcome. In this study, our aim was to assess ADA trough serum levels and the presence of AAA according to disease activity and clinical response during long-term follow-up in a series of patients with CD treated with ADA monotherapy. MATERIAL AND METHODS: We prospectively evaluated 23 consecutive, infliximab-na\uefve CD patients who achieved clinical remission/response after induction and were in maintenance treatment with ADA, and who were followed-up for at least 72 weeks. Blood samples were drawn at standardized time points to assess ADA through levels, AAA. RESULTS: At week 48, we found significantly (p\u2009=\u20090.027) different ADA trough serum levels in patients in remission (10.1\u2009mcg/mL), mild (7.4\u2009mcg/mL), and moderate/severe disease (4.5\u2009mcg/mL). Median ADA trough levels were significantly lower in patients with AAA (3.7\u2009mcg/mL versus 9.3\u2009mcg/mL, p\u2009=\u20090.006). At the end of follow-up (median 102 weeks, range 73-112 weeks), ADA trough serum concentrations were significantly higher (11.9\u2009mcg/mL) as compared to patients with mild and moderate/severe disease (5.5\u2009mcg/mL, p\u2009=\u20090.0002). Furthermore, median ADA trough concentrations showed a trend towards lower levels in AAA positive patients (5.2\u2009mcg/mL versus 7.2\u2009mcg/mL, p\u2009=\u20090.371). CONCLUSIONS: Our results emphasize the relevance of therapeutic drug monitoring in CD patients on biologic treatment. ADA trough serum levels and the presence of AAA are important features in the management of patients on ADA treatment

Cost per care of the first year of direct antiviral agents in the Liguria Region: a multicenter analysis

Giovanni Cenderello,1 Caterina Fanizza,2 Simona Marenco,3 Laura Ambra Nicolini,4 Stefania Artioli,5 Isabella Baldissarro,3 Chiara Dentone,6 Pasqualina De Leo,7 Antonio Di Biagio4 1SC Malattie Infettive, EO Ospedali Galliera, 2Rete ligure HIV, 3SSD Epatologia, AOU S. Martino, 4Clinica Malattie Infettive, AOU S. Martino, Genoa, 5SC Malattie Infettive ASL5 La Spezia, 6SC Malattie Infettive, ASL‑1, Sanremo, 7SC Malattie Infettive ASL2, San Paolo, Savona, Italy Aims: Despite the remarkable efficacy shown in clinical practice, concerns have been raised about the costs associated with direct antiviral agent (DAA) therapy. This article presents the real-life costs for DAA treatment sustained by the Italian National Health Service in the Liguria Region (Northern Italy).Methods: A retrospective analysis of the cost per care sustained for DAA treatment, relating to the period from January 1 to December 31, 2015 in five centers in Liguria was performed. All patients undergoing DAA-based treatments for hepatitis C virus (HCV) infection were enrolled. On-treatment costs included: HCV treatment, laboratory test, outpatient services, attended visits, drugs used for the management of adverse events (erythropoietin, albumin or red blood cell packs) and inpatient service admissions.Results: In total, 327 patients were enrolled. No difference in terms of sustained virologic response (SVR) rate among different treatments was reported. The majority (85.0%) of patients did not report any side effects and only 15 (4.6%) required hospital admission. Forty-two patients (12.8%) required high-cost drugs for the management of adverse events. The overall cost sustained was €14,744,433. DAA±ribavirin (RBV) accounted for the wide majority of this cost (98.9%; €14,585,123). Genotype (GT) 1, the most commonly treated GT, was associated with an average cost of €43,445 per patient. Detailed analysis of the costs for GT 1 showed the treatment based on ritonavir boosted paritaprevir/ombitasvir + dasabuvir±RBV with an average cost of €24,978 (RBV+) and €25,448 (RBV−) per patient was the most cost-effective. The average cost per SVR was €48,184. Once again, the ritonavir boosted ­paritaprevir/ombitasvir + dasabuvir regimen was associated with the lowest cost/SVR (€25,448/SVR [GT 1b] and similar results for other GTs).Conclusion: Antiviral regimen is the major contributor to costs in the treatment of HCV infection. Appropriate regimen selection could result in a major cost saving, which can be reinvested to allow more patients to be treated. Keywords: HCV treatment, HCV costs, cost efficac