RESUMEN
BACKGROUND AND AIMS: The clinical spectrum of human infection by HEV ranges from asymptomatic to severe acute hepatitis. Furthermore, HEV can cause diverse neurological manifestations, especially Parsonage-Turner syndrome. Here, we used a large-scale human genomic approach to search for genetic determinants of severe clinical presentations of HEV infection. APPROACH AND RESULTS: We performed whole genome sequencing in 3 groups of study participants with PCR-proven acute HEV infection: (1) 24 patients with symptomatic acute hepatitis E; (2) 12 patients with HEV-associated Parsonage-Turner syndrome; and (3) 16 asymptomatic blood donors (controls). For variant calling and annotation, we used GATK4 best practices followed by Variant Effect Predictor (VEP) and Annovar. For variant classification, we implemented the American College of Medical Genetics and Genomics/Association for Molecular Pathology Bayesian classification framework in R. Variants with a probability of pathogenicity >0.9 were considered damaging. We used all genes with at least 1 damaging variant as input for pathway enrichment analyses.We observed a significant enrichment of type I interferon response pathways in the symptomatic hepatitis group: 10 out of 24 patients carried a damaging variant in one of 9 genes encoding either intracellular viral sensors ( IFIH1 , DDX58 , TLR3 , POLR3B , POLR3C ) or other molecules involved in type I interferon response [interferon regulatory factor 7 ( IRF7 ), MYD88 , OAS3 , GAPDH ]. We did not find any enriched pathway in the Parsonage-Turner syndrome group or in the controls. CONCLUSIONS: Our results highlight the essential role of type I interferon in preventing symptomatic acute hepatitis E.
RESUMEN
BACKGROUND: Ethnicities differ in prevalence of blood groups and antigens. Substantial donor-recipient mismatch within mixed-ethnic societies may render certain recipients at higher risk for alloimmunization. Data regarding antigen distribution within Switzerland by ethnicity is limited. We examined immigration patterns against the distribution of ABO blood groups using large cross-sectional Swiss samples spanning 70 years. METHODS: Historical ABO blood group distribution data (1940-1945) from Swiss army personnel (n = 275,664) were sourced from the literature. Recent blood group phenotypes of 122,925 individuals who presented themselves at army recruitment centers (2004-2015) were obtained, alongside a validation sample of 175,202 patients from a university hospital. Two-sample tests with z-statistics assessing blood groups between samples were used. RESULTS: The respective proportions of A (47.2% and 45.2%), B (8.4% and 9.8%), and AB (3.0 and 4.1) in the historical and recent army samples were significantly different (p < 0.001), while group O was not. Conclusion: ABO blood groups in Switzerland have remained stable despite substantial immigration with a changing foreign-national profile. Further research is needed to improve the understanding of antigen differences in newly introduced ethnic groups. Blood product requirements and public health initiatives aimed at recruiting blood donors would benefit from this information.