Background Increased expression of B cell activating factor (BAFF or B lymphocyte stimulator) may explain the B cell activation characteristic of primary Sjögren's syndrome (pSS). Objectives To evaluate the efficacy and safety of belimumab, targeting BAFF, in patients with pSS. Methods Patients were included in this bi-centric prospective 1-year open-label trial if they fulfilled American European Consensus group criteria, were anti-Sjögren's syndrome A-positive and had current systemic complications or salivary gland enlargement, or early disease (25% improvement in any B cell activation biomarker values. Results Among 30 patients included, the primary end-point was achieved in 18 (60%). The mean (SD) European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index decreased from 8.8 (7.4) to 6.3 (6.6) (p=0.0015) and EULAR) Sjögren's Syndrome Patient Reported Index from 6.4 (1.1) to 5.6 (2.0) (p=0.0174). The mean dryness, fatigue and pain VAS varied from 7.8 (1.8) to 6.2 (2.9) (p=0.0021), 6.9 (1.8) to 6.0 (2.2) (p=0.0606) and 4.6 (2.6) to 4.7 (2.4) (p=0.89), respectively. Salivary flow and Schirmer's test did not change. Conclusions These encouraging results justify future randomised controlled trials of belimumab in a selected target population of pSS patients most likely to benefit from treatment.

Objective. Rituximab, an anti-CD20 monoclonal antibody, has been used in lupus nephritis and membranous idiopathic nephropathy and has proved effective in non-renal manifestations of type II mixed cryoglobulinaemia (MC) syndrome. We investigated the possible efficacy and safety of rituximab in the treatment of cryoglobulinaemic nephritis. Methods. Five patients with active, biopsy-proven, glomerulonephritis in hepatitis C virus (HCV)-related type II MC syndrome were treated with four weekly infusions of rituximab (375 mg/m²) in monotherapy, without steroids whenever possible. Rituximab was the first-line therapy in three cases. Results. A rapid and sustained renal response was observed in all patients, in one of them without retreatment up to the last follow-up (month 21+). Renal biopsy was repeated after 6 months in one patient and histopathological improvement was documented. Three patients relapsed, at months +5, +7 and +12 of follow-up, respectively. Two of them were then retreated with rituximab and again presented a rapid improvement in renal function. Maintenance therapy with rituximab was performed in two patients: nephritis remission was maintained in both. Fc-γ receptor 3a (FcγRIIIa) genotype characterization was consistent with the clinical response observed. Rituximab also proved effective against other active MC manifestations, when present. No major side-effects occurred and steroids were not required in the follow-up. Conclusions. Rituximab may provide effective and safe therapy in type II MC-related glomerulonephritis, possibly as first-line therapy, avoiding steroids and hazardous immunosuppressive treatment.

Objective. Primary SS is characterized by an increased risk of lymphoma in patients with prelymphomatous manifestations (i.e. myoepithelial sialadenitis or mixed cryoglobulinaemia). Serum B-lymphocyte stimulator (s-BLyS) levels in SS-related B-cell lymphoproliferative disorders were studied by integrating the results with the disease activity score and with molecular analyses of B-cell expansion in the salivary glands.

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.

Objectives. To investigate the role of B-Lymphocyte stimulator (BLyS) in mixed cryoglobulinaemia syndrome (MCsn), a systemic vasculitis associated with a high risk to develop lymphoma, since BLyS up-regulation may favour both autoimmunity and lymphoproliferation.

Objectives. We explored clinical factors associated with a major response to rituximab (RTX) (e.g. ACR ⩾50, and European League against Rheumatism (EULAR) moderate to good response) in patients with active long-standing RA and inadequate response to anti-TNF agents or traditional DMARDs. Methods. RTX was used in 110 RA patients in six different Italian centres. The mean disease activity score on 28 joints (DAS28) was 6.4 ± 0.99 and the mean HAQ was 1.63 ± 0.68 at baseline. Thirty-two patients (29.1%) underwent RTX after the failure of DMARD therapy, 37 (33.6%) had failed or were intolerant to at least two anti-TNF agents, and 41 (37.3%) had failed or were intolerant to one anti-TNF agent. Univariate and multivariate analyses were performed. Results. The number of previous anti-TNF agents (P = 0.043), HAQ (P = 0.023), RF positivity (P < 0.0001) and anti-cyclic citrullinated peptide (anti-CCP) positivity (P = 0.003) were associated with ACR response ⩾50 between month +4 and month +6 after starting RTX by univariate analysis. Multivariate analysis confirmed that a lower HAQ, a lower number of anti-TNF agents failed before RTX and RF positivity, but not anti-CCP positivity, were the selected variables associated with an ACR response ⩾50, with an accuracy of 84% of the model. Only RF positivity correlated with EULAR moderate to good response both in the univariate and in the multivariate analysis, with an accuracy of 79% of the model. Conclusion. RF-positive rather than anti-CCP-positive RA patients with lower baseline disability and a lower number of previously failed TNF blockers may be the best candidates to RTX.