Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: An international case-cohort study

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts. A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (\u3baw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the Cindex. A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (\u3baw=0.65, IQR 0.53-0.72, p20 years of experience (C-index=0.72, IQR 0.0-0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70-0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72-0.75). Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts

Local Autoantigen Expression as Essential Gatekeeper of Memory T-Cell Recruitment to Islet Grafts in Diabetic Hosts

Transplantation and autoimmunit

Local Autoantigen Expression as Essential Gatekeeper of Memory T-Cell Recruitment to Islet Grafts in Diabetic Hosts

It is generally believed that inflammatory cues can attract noncognate, “bystander” T-cell specificities to sites of inflammation. We have shown that recruitment of naive and in vitro activated autoreactive CD8(+) T cells into endogenous islets requires local autoantigen expression. Here, we demonstrate that absence of an autoantigen in syngeneic extrapancreatic islet grafts in diabetic hosts renders the grafts “invisible” to cognate memory (and naive) T cells. We monitored the recruitment of islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)(206–214)-reactive CD8(+) T cells into IGRP(206–214)-competent and IGRP(206–214)-deficient islet grafts in diabetic wild-type or IGRP(206–214)(−/−) nonobese diabetic hosts (harboring either naive and memory T cells or only naive IGRP(206–214)-specific T-cells, respectively). All four host–donor combinations had development of recurrent diabetes within 2 weeks. Wild-type hosts recruited IGRP(206–214)-specific T cells into IGRP(206–214)(+/+) but not IGRP(206–214)(−/−) grafts. In IGRP(206–214)(−/−) hosts, there was no recruitment of IGRP(206–214)-specific T cells, regardless of donor type. Graft-derived IGRP(206–214) activated naive IGRP(206–214)-specific T cells, but graft destruction invariably predated their recruitment. These results indicate that recurrent diabetes is exclusively driven by autoreactive T cells primed during the primary autoimmune response, and demonstrate that local antigen expression is a sine qua non requirement for accumulation of memory T cells into islet grafts. These findings underscore the importance of tackling autoreactive T-cell memory after β-cell replacement therapy