Seattle Protocol Is More Effective in Detection of Dysplasia Compared to Technology-Assisted Targeted Biopsies in Patients with Barrett’s Esophagus

Background and aims: With the development of narrow-band imaging (NBI) in the endoscopic evaluation of patients with Barrett’s esophagus (BE), the role of random biopsies according to the Seattle protocol (SP) has been questioned. We aim to compare the utility of advanced imaging to SP in patients with BE. Methods: A prospective cohort of patients with proven BE was retrospectively analyzed. All biopsies were reviewed by an expert GI pathologist. Advanced imaging was tandemly used with SP in each endoscopic procedure. Results: A total of 155 out of 340 patients (45.5%) with BE were diagnosed with dysplasia during a median follow-up of 4.7 years (IQR 3.4–6.1 years) and were part of the statistical analysis. A total of 82 patients had a diagnosis of dysplasia at presentation, whereas 84 patients developed dysplasia during follow up. A total of 67 out of 82 patients with dysplasia at presentation (81.7%), and 65 out of 84 patients that were diagnosed with dysplasia during follow-up (77.4%) were diagnosed using SP. In addition, whereas all the events of EAC were diagnosed using targeted biopsies, 57.1% of the events of HGD and 86.3% of LGD were diagnosed using SP. Conclusion: Our findings demonstrate the significance of SP in the detection of low- and high-grade dysplasia in patients with BE. SP should remain the mainstay of endoscopic surveillance in this population

Lack of conventional dendritic cells is compatible with normal development and T cell homeostasis, but causes myeloid proliferative syndrome

Dendritic cells are critically involved in the promotion and regulation of Tcell responses. Here, we report a mouse strain that lacks conventional CD11chi dendritic cells (cDCs) because of constitutive cell-type specific expression of a suicide gene. As expected, cDC-less mice failed to mount effective Tcell responses resulting in impaired viral clearance. In contrast, neither thymic negative selection nor T regulatory cell generation or Tcell homeostasis were markedly affected. Unexpectedly, cDC-less mice developed a progressive myeloproliferative disorder characterized by prominent extramedullary hematopoiesis and increased serum amounts of the cytokine Flt3 ligand. Our data identify a critical role of cDCs in the control of steady-state hematopoiesis, revealing a feedback loop that links peripheral cDCs to myelogenesis through soluble growth factors, such as Flt3 ligand

Dendritic cells ameliorate autoimmunity in the CNS by controlling the homeostasis of PD-1 receptor(+) regulatory T cells

Mature dendritic cells (DCs) are established as unrivaled antigen-presenting cells (APCs) in the initiation of immune responses, whereas steady-state DCs induce peripheral T cell tolerance. Using various genetic approaches, we depleted CD11c(+) DCs in mice and induced autoimmune CNS inflammation. Unexpectedly, mice lacking DCs developed aggravated disease compared to control mice. Furthermore, when we engineered DCs to present a CNS-associated autoantigen in an induced manner, we found robust tolerance that prevented disease, which coincided with an upregulation of the PD-1 receptor on antigen-specific T cells. Additionally, we showed that PD-1 was necessary for DC-mediated induction of regulatory T cells. Our results show that a reduction of DCs interferes with tolerance, resulting in a stronger inflammatory response, and that other APC populations could compensate for the loss of immunogenic APC function in DC-depleted mice