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Objective To determine the prevalence of upregulation of interferon (IFN) type I inducible genes, the so called ‘IFN type I signature’, in CD14 monocytes in 69 patients with primary Sjögren's syndrome (pSS) and 44 healthy controls (HC) and correlate it with disease manifestations and expression of B cell activating factor (BAFF). Methods Expression of IFI44L, IFI44, IFIT3, LY6E and MX1 was measured using real time quantitative PCR in monocytes. Expression values were used to calculate IFN type I scores for each subject. pSS patients positive for the IFN type I signature (IFN score≥10) and patients negative for the signature (IFN score

Background and aim Mesenchymal stromal cells (MSCs) are pluripotent cells that have immunosuppressive effects both in vitro and in experimental colitis. Promising results of MSC therapy have been obtained in patients with severe graft versus host disease of the gut. Our objective was to determine the safety and feasibility of autologous bone marrow derived MSC therapy in patients with refractory Crohn9s disease. Patients and intervention 10 adult patients with refractory Crohn9s disease (eight females and two males) underwent bone marrow aspiration under local anaesthesia. Bone marrow MSCs were isolated and expanded ex vivo. MSCs were tested for phenotype and functionality in vitro. 9 patients received two doses of 1–2×10 6 cells/kg body weight, intravenously, 7 days apart. During follow-up, possible side effects and changes in patients9 Crohn9s disease activity index (CDAI) scores were monitored. Colonoscopies were performed at weeks 0 and 6, and mucosal inflammation was assessed by using the Crohn9s disease endoscopic index of severity. Results MSCs isolated from patients with Crohn9s disease showed similar morphology, phenotype and growth potential compared to MSCs from healthy donors. Importantly, immunomodulatory capacity was intact, as Crohn9s disease MSCs significantly reduced peripheral blood mononuclear cell proliferation in vitro. MSC infusion was without side effects, besides a mild allergic reaction probably due to the cryopreservant DMSO in one patient. Baseline median CDAI was 326 (224–378). Three patients showed clinical response (CDAI decrease ≥70 from baseline) 6 weeks post-treatment; conversely three patients required surgery due to disease worsening. Conclusions Administration of autologous bone marrow derived MSCs appears safe and feasible in the treatment of refractory Crohn9s disease. No serious adverse events were detected during bone marrow harvesting and administration.

Over the past decades, incidence rates of immune-mediated inflammatory diseases including asthma and IBDs have been rising steadily in both Western and low/middle-income countries.1 The cause of this increase has been a topic of intense investigation, and a variety of factors such as diet, hygiene and pollution have been implicated. One of the most clear correlations between disease and environment is that between exposure to house dust mite (HDM) and asthma exacerbations.2 HDM contains several antigens, including Der p1 , a cysteine protease that damages the airway epithelium thus allowing antigens to pass into the pulmonary tissue.3 In atopic individuals, this results in a potent IgE-mediated specific anti- Der …

Bile salts are produced in the liver and delivered to the duodenum, where they emulsify lipids to facilitate absorption. After passing through the small intestine, the majority of bile salts are reabsorbed for recycling in the terminal ileum. One of the key receptors involved in this reabsorption is the farnesoid X receptor (FXR), a member of the family of nuclear receptors which function as transcription factors. FXR signalling regulates target genes involved in bile acid synthesis (CYP7a), efflux (ABCB11) and absorption of conjugated bile acids (IBABP). In line with the role of FXR in bile homeostasis, FXR–/– mice were initially described to have aberrancies in bile acid and lipid homeostasis, with elevated cholesterol levels in both liver and serum.1 Interestingly, when these animals were followed up for longer periods, hepatic levels of the proinflammatory cytokines interferon γ, interleukin 6 (IL-6) and tumour necrosis factor α (TNFα) were increased, suggesting an additional role for FXR in immunoregulation.2 This role was further confirmed in ApoE–/– mice, which develop aortic plaques after being fed a high-cholesterol diet. Administration of an FXR agonist reduced plaque formation as well as intraplaque expression of inflammatory mediators, supporting an immunomodulatory …