Coeliac disease (CD) is a chronic immune-mediated disease triggered by the ingestion of gluten. It has an estimated prevalence of approximately 1% in European populations. Specific HLA-DQA1 and HLA-DQB1 alleles are established coeliac susceptibility genes and are required for the presentation of gliadin to the immune system resulting in damage to the intestinal mucosa. In the largest association analysis of CD to date, 39 non-HLA risk loci were identified, 13 of which were new, in a sample of 12 014 individuals with CD and 12 228 controls using the Immunochip genotyping platform. Including the HLA, this brings the total number of known CD loci to 40. We have replicated this study in an independent Irish CD case–control population of 425 CD and 453 controls using the Immunochip platform. Using a binomial sign test, we show that the direction of the effects of previously described risk alleles were highly correlated with those reported in the Irish population, (P=2.2 × 10−16). Using the Polygene Risk Score (PRS) approach, we estimated that up to 35% of the genetic variance could be explained by loci present on the Immunochip (P=9 × 10−75). When this is limited to non-HLA loci, we explain a maximum of 4.5% of the genetic variance (P=3.6 × 10−18). Finally, we performed a meta-analysis of our data with the previous reports, identifying two further loci harbouring the ZNF335 and NIFA genes which now exceed genome-wide significance, taking the total number of CD susceptibility loci to 42.
Background Coeliac disease (CD) is associated with an increased risk of other immune-mediated conditions. Aim: To investigate the prevalence of coexistent immune-mediated diseases in CD patients, and changes in the prevalence of autoimmune thyroidal diseases over the last 50 years. Methods Medical record data were collected retrospectively from 749 CD patients in Ireland. Prevalence of autoimmune diseases was compared with previously published results from general populations. Patients were divided into four groups based on the year of diagnosis to analyse changes in the prevalence of autoimmune thyroidal disease over time. Results Median age at the time of CD diagnosis was 56 years (range 18–91 years). A total of 233 (31.1%) patients had a coexistent immune-mediated condition (IMC). Autoimmune thyroidal diseases were seen in 149 (19.9%) patients, hypothyroidism in 110 (14.7%), type 1 diabetes in 27 (3.6%), psoriasis in 20 (2.7%), inflammatory bowel disease in 14 (1.9%) and rheumatoid arthritis in 12 (1.6%). All conditions were more common in CD patients than in the general population. Type 1 diabetes was diagnosed mainly before CD, whereas there was no such trend in other conditions. Autoimmune thyroidal diseases became less common in female CD patients over time. Conclusions Prevalence of autoimmune diseases is increased in adult CD patients compared with the general population. However, concomitant autoimmune thyroidal diseases became less common over time in women.
Objectives
One of the striking features of splenic imaging is variable heterogeneous gyriform arterial enhancement on dynamic computed tomography (CT). We speculated that these patterns of arterial enhancement may reflect changes in splenic micro-circulation related to changes in portal venous pressure.
Patients and methods
To test this hypothesis, we evaluated arterial phase CT scans performed before and after liver transplantation (n=91), as this is the most effective way of alleviating portal hypertension. We developed novel grading systems to assess heterogeneity. Two control groups were used: patients with cirrhosis undergoing transarterial chemoembolization (TACE) (n=28) and patients with cirrhosis on the liver transplant waiting list who had repeated CT scans (n=28).
Results
Splenic arterial heterogeneity increased in 55% of transplant patients compared with 14% in the TACE patients and 4% in the waiting list patients (P<0.0001). Mean Hounsfield units in areas of splenic enhancement were 71.7±2 before transplant and 90.1±2.5 after transplant (P<0.01). In contrast, there were no significant changes following TACE (86.3±4.2 vs. 83.5±4.5; P=NS) or in waiting list patients (80.9±4.6 vs. 73.8±3.7; P=NS).
Conclusion
We have shown the heterogeneous gyriform enhancement patterns significantly increase following liver transplantation but not after TACE or in waiting list patients. We suggest that these changes are due to the reduction in portal venous pressure and likely reflect changes in splenic micro-circulation. These changes may be important in the pathophysiology of hypersplenism.
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