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BACKGROUND AND OBJECTIVE BLyS (B-Lymphocyte stimulator) is over-expressed in several tumoral settings, with direct or indirect effects on neoplastic proliferation and possibly representing a therapeutic target. In this study, we explored the role of BLyS in a large population of patients with neuroendocrine tumors (NETs). METHODS The study analyzed the stored sera of 124 consecutive unselected patients with NETs: 36 lung carcinoids (24 typical, 12 atypical), 47 gastroenteric tract and 41 pancreatic (30 non-functioning and 11 functioning: 9 insulinomas, 2 glucagonomas). In 23 cases, BLyS was repeatedly assessed during the follow-up and the disease was monitored (progression, stabilization or remission) according to the RECIST criteria. Patients were compared to 92 age and sex-matched blood donors (BDs). Serum levels of BLyS and Chromogranin A (CgA) were analyzed by ELISA. RESULTS NET patients showed significantly higher BLyS levels than BDs (1274±809 pg/ml vs. 587±173 pg/ml; p

Purpose To explore the role of plasmatic platelet-activating factor acetylhydrolase (PAF-AH), a marker of cardiovascular risk, in patients with anti-phospholipid antibodies (aPL). Methods PAF-AH activity was assessed in a series of 167 unselected patients screened for aPL in a context of thrombotic events, risk of thrombosis or obstetric complications and in 77 blood donors. Results 116/167 patients showed positive results for at least one aPL among IgG/IgM anti-prothrombin/phosphatidylserine (aPS/PT), anti-cardiolipin (aCL), anti-beta2-glycoprotein I (aβ2GPI) or lupus anticoagulant (LAC), while 51/167 patients resulted aPL-negative. LAC+ patients disclosed higher PAF-AH than LAC-negative (22.1 ± 6.4 nmol/min/ml vs. 19.5 ± 4.1 nmol/min/ml; p = 0.0032), and aPL-negative patients (p = 0.03). Patients presenting positive IgG aβ2GPI disclosed higher PAF-AH than patients with only IgM aβ2GPI-positive antibodies (23.1 ± 7.2 nmol/min/ml vs. 20.1 ± 5.3 nmol/min/ml; p = 0.035), as well as than patients showing only isolated LAC, aCL or aPS/PT (16.9 ± 3.8 nmol/min/ml; p = 0.003). Conclusions PAF-AH plasmatic activity is particularly up-regulated in LAC+ and in aβ2GPI IgG+ patients, possibly representing an alternative prognostic biomarker for the therapeutic management of APS patients.

The purpose of this study is to characterize synovial fluid- (SF-) derived exosomes of patients with gonarthrosis comparing two methods of isolation and to investigate their immune regulatory properties. Extracellular vesicles (EVs) have been isolated from inflamed SF by polymer precipitation method and quantified by Exocet kit and by nanoparticle tracking analysis. Vesicles expressed all the specific exosomal markers by immunoblot and FACS. After isolation with Exoquick, a relevant contamination by immune complexes was detected, which required further magnetic bead-based purification to remove. SF-derived exosomes significantly stimulated the release of several inflammatory cytokines and chemokines and metalloproteinases by M1 macrophages but did not influence the expression of CD80 and CD86 costimulatory molecules. In conclusion, we characterized purified exosomes isolated from inflamed SF and demonstrate that purified exosomes are functionally active in their ability to stimulate the release of proinflammatory factors from M1 macrophages. Our data indicate that SF-derived exosomes from gonarthrosis patients play a role in disease progression.

Background and Objective: In Alzheimer disease (AD) inflammation becomes evident throughout the course of the disease. However, the association between inflammation, cognitive impairment, and cerebrospinal biomarkers (Aβ42, t-tau, p-tau181, and Aβ42/p-tau181 ratio) is poorly understood. Methods: A large panel of inflammatory cytokines (interleukin [IL]-1β, IL-1ra, IL-2, IL-4, IL-6, IL-10, IL-17, interferon-γ, tumor necrosis factor-α, and vascular endothelial growth factor) was analyzed using a multiplex immunoassay in 27 patients with a diagnosis of AD dementia and in 18 control subjects. In a subgroup with available cerebrospinal fluid (CSF) samples, cytokines in serum were correlated with the levels of neurodegenerative CSF biomarkers (Aβ42, t-tau, p-tau181, and Aβ42/p-tau181 ratio). Results: Compared to control subjects, AD patients showed a significant upregulation of IL-10, IL-1β, and IL-17 serum levels. Several cytokines appeared intercorrelated, and IL-10 in particular presented a significant inverse correlation with CFS levels of Aβ42 and the Aβ42/p-tau ratio. Conclusion: Our findings indicate that serum levels of IL-10 may represent a possible peripheral expression of amyloid beta deposition in AD patients.

Background: A reliable identification of ADAb represents a fundamental tool in the followup of patients under treatment with anti-TNF drugs. Objectives: To compare three immunoenzymatic assays for anti-adalimumab antibodies (AAA) detection. Methods: The study was performed in 40 patients with chronic inflammatory polyarthritis, comprising both patients showing a good response to adalimumab (ADL) and patients who lost response or did not respond to ADL, recently or in the past (retrospective study). Thus, sera were collected before ADL administration or well after ADL discontinuation. AAA were analysed by three different bridging ELISAs, following manufacturers’ instructions. Results: All methods disclosed negative results in responder patients and univocally recognized 11/31 (35.5%) AAA highpositive samples in non-responder patients, including several cases that had discontinued ADL for a long time (range 3-48 months). Among the overall non-responder patients, 10/31 (32.3%) disclosed concordant clear-cut AAA-negative results, while negative versus low-positive or borderline results were found in another ten non-responder patients, indicating slight differences in sensitivity between the methods, especially in patients who were analysed retrospectively. Methotrexate in combination therapy with ADL tended to be more frequent in AAA-negative, than in AAA-positive patients (52.6% vs. 25%; p=ns). Conclusions: The three bridging ELISA methods under study showed a good agreement and were able to identify uniquely the presence of high positive AAA, even after a long time since ADL discontinuation.