A partial form of inherited human USP18 deficiency underlies infection and inflammation

International audienceHuman USP18 is an interferon (IFN)-stimulated gene product and a negative regulator of type I IFN (IFN-I) signaling. It also removes covalently linked ISG15 from proteins, in a process called deISGylation. In turn, ISG15 prevents USP18 from being degraded by the proteasome. Autosomal recessive complete USP18 deficiency is life-threatening in infancy owing to uncontrolled IFN-I–mediated autoinflammation. We report three Moroccan siblings with autoinflammation and mycobacterial disease who are homozygous for a new USP18 variant. We demonstrate that the mutant USP18 (p.I60N) is normally stabilized by ISG15 and efficient for deISGylation but interacts poorly with the receptor-anchoring STAT2 and is impaired in negative regulation of IFN-I signaling. We also show that IFN-γ–dependent induction of IL-12 and IL-23 is reduced owing to IFN-I–mediated impairment of myeloid cells to produce both cytokines. Thus, insufficient negative regulation of IFN-I signaling by USP18-I60N underlies a specific type I interferonopathy, which impairs IL-12 and IL-23 production by myeloid cells, thereby explaining predisposition to mycobacterial disease

Orofacial manifestations in outpatients with anorexia nervosa and bulimia nervosa focusing on the vomiting behavior

Objective: This case-control study aims to evaluate the oral health status and orofacial problems in a group of outpatients with eating disorders (ED)—either anorexia nervosa (AN) or bulimia nervosa (BN)—further focusing on the influence of vomit. Materials and methods: Fifty-five women outpatients with AN or BN diagnosis were invited to participate, of which 33 agreed. ED outpatients and matched controls were submitted to a questionnaire and clinical oral examination. Results: Multivariate analysis identified a significantly higher incidence of teeth-related complications (i.e., tooth decay, dental erosion, and self-reported dentin hypersensitivity), periodontal disease, salivary alterations (i.e., hyposalivation and xerostomia), and oral mucosa-related complications in ED outpatients. Dental erosion, self-reported dentin hypersensitivity, hyposalivation, xerostomia, and angular cheilitis were found to be highly correlated with the vomiting behavior. Conclusions: ED outpatients were found to present a higher incidence of oral-related complications and an inferior oral health status, compared to gender- and age-matched controls. Alterations verified within outpatients were acknowledged to be quite similar to those previously reported within inpatients, in both of nature and severity, thus sustaining that the cranio-maxillofacial region is significantly affected by ED, even in the early/milder forms of the condition, as expectedly verified within outpatients.The work was supported by the Faculty of Dental Medicine, U. Porto