BackgroundChronic autoimmune urticaria (CAU) is a common skin disease and remains unclear understanding of pathogenesis in the vast majority of cases. In order to explore a new therapy for CAU, the current study was performed to investigate the possible functioning of the Oncostatin M receptor (OSMR) gene in the autoimmunity of CAU via regulation of the JAK/STAT3 signaling pathway.MethodsCAU skin tissues from 24 CAU patients and normal skin tissues from normal subjects were collected. Hematoxylin-eosin (HE) staining was conducted to count eosinophils, and immunohistochemistry was carried out to detect the positive rate of OSMR expression in two kinds of skin tissues. A total of 72 Kunming (KM) mice were selected, and 60 mice were used for establishing CAU models and later transfected with different plasmids. The expression of inflammatory factors was evaluated by enzyme-linked immunosorbent assays (ELISA). Expressions of janus kinase (JAK), signal transducer and activator of transcription 3 (STAT3), interferon-stimulated gene 15 (ISG15), CT10-regulated kinase (CRK), and interferon regulatory factor 9 (IRF9) were identified using Western blot assay and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Epithelial cell proliferation was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, and cell cycle distribution and cell apoptosis were assessed using flow cytometry.ResultsThe findings confirm that OSMR protein expression and histamine release rate are highly elevated in human CAU skin tissues, and the expression of the JAK/STAT3 signaling pathway-related genes (OSMR, JAK2, STAT3, ISG15, CRK and IRF9) was up-regulated. OSMR gene silencing in CAU mice significantly decreases the content of inflammatory factors (IL-1, IL-6, IFN-γ, and IgE), the number of eosinophils, and reduces the expression of the JAK/STAT3 signaling pathway related genes, and further enhances cell proliferation, promotes cell cycle entry and inhibits apoptosis of epithelial cells.ConclusionAll aforementioned results indicate that OSMR gene silencing inhibits the activation of the JAK/STAT3 signaling pathway, thereby suppressing the development of CAU.
A 19-month-old boy of a consanguineous marriage presented with skin lesions and joint contracture since birth. The activity of his shoulder joint was restricted at birth followed by the knees, finger joints, and spine over the next several months. Red papules were first detected on the forehead, and then appeared on his back, buttocks, and thighs. His dietary intake was limited by severe gingival hyperplasia. He had already had 4 episodes of recurrent pneumonia. He had 2 healthy sisters and 1 brother with similar manifestations, who died of recurrent pneumonia at age 31 months.On examination, he was malnourished. Lung auscultation revealed subpulmonary moist rales. The patient was constricted to a froglike body posture owing to contracture of his large joints. Severe gingival hyperplasia caused his mouth to be partially open (Figure 1). Skin examination revealed many pearly papules in the perianal area and on the thighs (Figure 2). A 5-cm firm mass was apparent on the occiput. Clawhand was noted.Routine blood testing results demonstrated mild hypochromic anemia, and his stool tested positive for blood. Chest radiography showed pneumonia. Osteoporosis of the extremities and thoracolumbar scoliosis was confirmed by radiographic findings. Skin biopsy from the thigh showed abundant hyaline material in the dermis with dispersed fibroblasts. Genome sequencing showed mutation of ANTXR2/CMG2, specifically a homozygous 1069delG in exon 13 resulting in a frame shift and premature stop codon. The clinical presentation and distinctive histologic findings suggested infantile systemic hyalinosis (ISH), and genetic testing confirmed the diagnosis.Infantile systemic hyalinosis is a rare autosomal recessive genetic disorder characterized by hyaline deposits in the dermis and other tissues with various organs involved. The clinical presentation includes typical skin lesions (pearly papules in the perianal area and on the thighs), gingival hypertrophy, scoliosis, persistent diarrhea, recurrent infection, and joint contracture.Infantile systemic hyalinosis, together with juvenile hyaline fibromatosis (JHF), are considered to be a spectrum of hyaline fibromatosis syndrome. 1 Mutations in the ANTXR2/CMG2 gene encoding capillary morphogenesis protein-2 contribute to the pathogenesis. 2 The capillary morphogenesis protein-2 binds to type IV collagen and laminin, 3 contributing to the adhesion of the basement membrane and extracellular matrix. The mutation disrupts basement membranes, resulting in abundant homogeneous hya-line deposits and a variety of clinical features including pearly papules, joint contracture, gingival hypertrophy, and osteoporosis.
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