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Objective. Several clinical studies have proposed the infusion of adipose mesenchymal stem cells (AMSCs) as an alternative therapy for joint diseases with inflammatory components, such as osteoarthritis. Indeed, AMSCs are able to stimulate tissue repair through a paracrine activity and the interaction with the inflammatory microenvironment seems to have a critical role. Design. To reproduce the inflammatory microenvironment, AMSCs were exposed to osteoarthritic synovial fluid (SF) for 48 h and the effect of their secretome on differentiation of monocytes (M0) into macrophages M1-like and mature dendritic cells (mDCs) was evaluated. Furthermore, the effect of the secretome of AMSCs exposed to SF was evaluated on the T cell population in terms of T cell proliferation and expansion of T regulatory cells (T reg). Results. Our data show that the exposure of AMSCs to SF activates cells and promotes the release of immunosuppressive factors, which induce macrophage polarization of M0 into the M2-like phenotype and inhibit differentiation of monocytes into mature dendritic cells (mDCs). Only the secretome of exposed AMSCs was able to inhibit T cell proliferation and promote T reg expansion. Conclusions. Our results suggest that the microenvironment plays a fundamental role for the development of anti-inflammatory and immunomodulatory properties of AMSCs.

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.

Background Belimumab is preliminary found to be effective in Sjogren9s syndrome (SS) (1). It was administered in 30 SS patients coming from two Centres (Udine, Italy and Paris, France) (1). The ESSDAI score and the serum levels of rheumatoid factor (RF) and IgM immunoglobulins were significantly affected by this treatment in the long term. Objectives The aim of this study is to report the one year follow-up data after the end of the BELISS study in the Italian cohort, in order to further support the benefits of belimumab in SS during treatment. Methods Clinical and laboratory data of 13 SS patients were collected at one year after the end of the belimumab treatment in the BELISS study. Importantly, no immunosuppressors were employed in all these patients after the end of the trial. Statistical comparisons by t-test or Wilcoxon test, were performed between data at month +12 after the end of the study, and data at the beginning and at the end of the trial itself (i.e., week 0 and 52). Results are reported as mean ± standard deviation. Results The ESSDAI score was 8,8±6,9 at baseline, 3,5±3,7 at week 52 (end of the trial) and 7,0±5,7 at month 12 after the end of the trial (baseline vs. month +12, p=0,2; week 52 vs. month +12, p=0,003). Thus, a significant increase in the ESSDAI score was observed between week 52 and month +12 after the end of the trial, with the mean score coming back in the range of moderate disease activity from the low level. RF was 93,7±101,2 IU/ml at baseline, 74,7±74,5 IU/ml at week 52, 174,1±220,3 IU/ml at month 12 after the end of the trial (baseline vs. month +12, p=0,5; week 52 vs. month +12, p=0,008). Thus, a significant increase in RF serum level was observed between week 52 and month +12 after the end of the trial, serum RF almost doubling the baseline level. IgM level was 2456±975,6 mg/dl at baseline, 2173±885,3 mg/dl at week 52, 2381,6±1152,4 mg/dl at month 12 after the end of the trial (baseline vs. month +12, p=0,3; week 52 vs. month +12, p=0,04). Thus, a significant increase in the IgM serum level was observed between week 52 and month +12 after the end of the trial, serum IgM coming back to the baseline level. BLyS level was 1211±429 pg/ml at baseline, 1704±1044 pg/ml at week 52 and 1896±950 pg/ml 12 months after belimumab suspension. Interestingly, BLyS levels were significantly higher even four weeks after the last belimumab infusion (week 52) if compared to baseline levels (p=0,04), and increased 12 months later (baseline vs. month +12 after the end of the trial, p=0,01; week 52 vs. month +12 after the end of the trial, p=0,2). Interestingly, the development of malignant B-cell lymphoma from non neoplastic parotid sialadenitis was observed in two patients two years after the end of the trial in both patients. Conclusions Worsening in systemic activity and in B-cell biomarkers occurs in SS after the suspension of belimumab, supporting the role of targeting BLyS in SS. A possible control of non malignant B cell lymphoproliferation in SS by belimumab is suggested. A more prolonged therapy with belimumab may be useful in SS. References Mariette X, et al. ARD 2013 Disclosure of Interest None declared

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.