The type of allergic sensitization is of central importance in the diagnosis and treatment of respiratory allergic diseases. At least 10% of the general population (and more than 50% of patients consulting for respiratory allergies) are polysensitized. Here, we review the recent literature on (i) the concepts of polysensitization, paucisensitization, co-sensitization, co-recognition, cross-reactivity, cross-sensitization, and polyallergy, (ii) the prevalence of polysensitization and (iii) the relationships between sensitization status, disease severity and treatment strategies. In molecular terms, clinical polysensitization can be divided into cross-sensitization (also known as cross-reactivity, in which the same IgE molecule binds to several allergens with common structural features) and co-sensitization (the simultaneous presence of different IgEs binding to allergens that may not necessarily have common structural features). There is a strong overall association between sensitization in skin prick tests and total IgE values but there is debate as to whether IgE thresholds are useful guides to the presence or absence of clinical symptoms in individual cases. Molecular information from component-resolved techniques appears to be of value for diagnosis and treatment decisions. Polysensitization develops over time and is a risk factor for respiratory allergy (being associated with disease severity) and therefore has clinical relevance for treatment decisions. The subterm polysensitization has been defined as polysensitization to between two and four allergens. Polyallergy is defined as clinically confirmed allergy to two or more allergens. Single-allergen grass pollen allergen immunotherapy (AIT) is safe and effective in polysensitized patients, whereas multi-allergen AIT requires more supporting evidence. Given that AIT may be more efficacious in moderate-to-severe disease than in mild disease, polysensitization could be an indication for this type of treatment. There is a need for flowcharts or decision trees for choosing the allergens for AIT in polysensitized patients and polyallergic patients.

Hepatitis E virus (HEV) genotype 3 is the most common genotype linked to HEV infections in Europe and America. Three major clades (HEV-3.1, HEV-3.2, and HEV-3.3) have been identified but the overlaps between intra-subtype and inter-subtype p-distances make subtype classification inconsistent. Reference sequences have been proposed to facilitate communication between researchers and new putative subtypes have been identified recently. We have used the full or near full-length HEV-3 genome sequences available in the Genbank database (April 2020; n = 503) and distance analyses of clades HEV-3.1 and HEV-3.2 to determine a p-distance cut-off (0.093 nt substitutions/site) in order to define subtypes. This could help to harmonize HEV-3 genotyping, facilitate molecular epidemiology studies and investigations of the biological and clinical differences between HEV-3 subtypes.

ObjectiveHepatitis E virus (HEV), one of the most common agent of acute hepatitis worldwide, is mainly transmitted enterically, via contaminated water for HEV genotypes 1 (HEV1) and HEV2, or by eating raw or undercooked infected meat for HEV genotype 3 (HEV3) and HEV4. However, little is known about how the ingested HEV reaches the liver or its ability to replicate in intestinal cells.DesignWe developed human primary cultures of small intestine epithelial cells and intestinal explants obtained from small bowel resections. The epithelial cells were also polarised on transwells. Cells were infected with Kernow-p6 strain or clinically derived virions.ResultsPrimary intestinal cells supported the growth of Kernow-p6 strain and HEV1 and HEV3 clinically derived virions. Polarised enterocytes infected with HEV1 and HEV3 strains released HEV particles vectorially: mostly into the apical compartment with a little basally. Iodixanol density gradient centrifugation of enterocyte-derived HEV virions gave bands at a density of 1.06–1.08 g/cm3, corresponding to that of quasi-enveloped HEV particles. Ribavirin therapy inhibited HEV excretion from the basal surface but not from the apical side of infected human enterocytes. HEV virions also infected intestinal tissue explants. Lastly, HEV RNA and antigen were detected in the intestinal crypts of a chronically infected patient.ConclusionHEV can replicate in intestinal cells and reaches the liver as quasi-enveloped virions.