Congenital deficiency reveals critical role of ISG15 in skin homeostasis.

Ulcerating skin lesions are manifestations of human ISG15 deficiency, a type I interferonopathy. However, chronic inflammation may not be their exclusive cause. We describe two siblings with recurrent skin ulcers that healed with scar formation upon corticosteroid treatment. Both had a homozygous nonsense mutation in the ISG15 gene, leading to unstable ISG15 protein lacking the functional domain. We characterized ISG15-/- dermal fibroblasts, HaCaT keratinocytes, and human induced pluripotent stem cell-derived vascular endothelial cells. ISG15-deficient cells exhibited the expected hyperinflammatory phenotype, but also dysregulated expression of molecules critical for connective tissue and epidermis integrity, including reduced collagens and adhesion molecules, but increased matrix metalloproteinases. ISG15-/- fibroblasts exhibited elevated ROS levels and reduced ROS scavenger expression. As opposed to hyperinflammation, defective collagen and integrin synthesis was not rescued by conjugation-deficient ISG15. Cell migration was retarded in ISG15-/- fibroblasts and HaCaT keratinocytes, but normalized under ruxolitinib treatment. Desmosome density was reduced in an ISG15-/- 3D epidermis model. Additionally, there were loose architecture and reduced collagen and desmoglein expression, which could be reversed by treatment with ruxolitinib/doxycycline/TGF-ß1. These results reveal critical roles of ISG15 in maintaining cell migration and epidermis and connective tissue homeostasis, whereby the latter likely requires its conjugation to yet unidentified targets.

Ultrasonography and computed tomography in patients with crystal induced arthropathy

To assess the different ultrasonography [US] and computed tomography [CT] findings in patients with crystal induced arthropathy. A total of 45 patients; 27 male and 18 female with joint effusion are enrolled in the study in the period between May 2008 to November 2012 by the cooperation of the Radiology and Rheumatology and Rehabilitation Departments, Sohag University Hospital All patients subjected to physical examination, ultrasonography; computed tomography; joint aspiration and analysis of aspirated fluid. Ages of the patients were between 40-73 years. Thirty sixth patients were proven to have crystals fluid analysis. About 90% of them diagnosed by CT and 86% diagnosed by US. Different types of calcification were found In 88% f patients. US show double contour sign in about14% of patients with MSU. Synovial hypertrophy was observed in about 28% of patients. Erosion was diagnosed better by CT than US and found in 80%." of patients. Uneven joint space was seen in 22% of patients. US and CT are very important in assessment of patients with crystal induced arthropathy