Abstract
Aim
To assess the pathobiological and translational importance of whole-blood transcriptomic analysis in inflammatory bowel disease IBD.
Methods
We analysed whole-blood expression profiles ...from paired-end sequencing in a discovery cohort of 590 Europeans recruited across six countries in the IBD Character initiative (newly diagnosed patients with Crohn’s disease CD; n = 156, ulcerative colitis UC; n = 167, and controls n = 267), exploring differential expression DESeq2, co-expression networks WGCNA, and transcription factor involvement EPEE, ChEA, DoRothEA. Findings were validated by analysis of an independent replication cohort 99 CD, 100 UC, 95 controls. In the discovery cohort, we also defined baseline expression correlates of future treatment escalation using cross-validated elastic-net and random forest modelling, along with a pragmatic ratio detection procedure.
Results
Disease-specific transcriptomes were defined in IBD 8697 transcripts, CD 7152, and UC 8521, with the most highly significant changes in single genes, including CD177 (log2-fold change LFC = 4.63, p = 4.05 × 10-118), MCEMP1 LFC = 2.45, p = 7.37 × 10-109, and S100A12 LFC = 2.31, p = 2.15 × 10-93. Significantly over-represented pathways included IL-1 p = 1.58 × 10-11, IL-4, and IL-13 p = 8.96 × 10-9. Highly concordant results were obtained using multiple regulatory activity inference tools applied to the discovery and replication cohorts. These analyses demonstrated central roles in IBD for the transcription factors NFE2, SPI1 PU.1, CEBPB, and IRF2, all regulators of cytokine signalling, based on a consistent signal across cohorts and transcription factor ranking methods. A number of simple transcriptome-based models were associated with the need for treatment escalation, including the binary CLEC5A/CDH2 expression ratio in UC (hazard ratio = 23.4, 95% confidence interval CI 5.3–102.0).
Conclusions
Transcriptomic analysis has allowed for a detailed characterisation of IBD pathobiology, with important potential translational implications.
Graphical Abstract
Graphical Abstract
Abstract This study reviewed records of all electrical incidents involving work-related injury to employees Electricité de France (EDF) from 1996 through 2005 and analysed data for 311 incidents. The ...results are compared with 1231 electrical incidents that occurred during 1970–1979 and 996 incidents during 1980–1989. A total of 311 electrical incidents were observed. The medical consequences of electrical incident remain severe and particularly, the current fatality rate (3.2%) is similar to that recorded in the 1980s (2.7%) and 1970s (3.3%). Among individuals with non-fatal incidents, any change has occurred in the prevalence of permanent functional sequelae (23.6% in the 1970s vs. 27.6% in the 1980s and 32.5% currently). An increase in the incidence of neuropsychiatric sequelae (5.4% in the 1980s vs . 13% currently) has been observed and they are now the second most common type of sequelae after those directly related to burns. Among the neurological sequelae, peripheral nervous system disorders are the most common, as observed in the 1980s. Since the definition of post-traumatic stress disorder (PTSD) has changed between the two periods, we can only report that the current prevalence of PTSD is 7.6%. This study emphasises the need for specific management of neurological and psychological impairments after electrical injuries, including especially early recognition and initiation of effective treatment.
PDF