Soluble CD93 in allergic asthma

Abstract

Jung-Won park 2,3 & Jae-Hyun Lee 2,3* CD93 has been shown critical roles in inflammatory and immune diseases. However, in allergic asthma, the potential roles of soluble CD93 (sCD93) have not been well studied. We conducted house dust mite (HDM) stimulation with Der p 1 in BEAS-2B and U937 cells, followed by treatment with dexamethasone or small interfering RNA against CD93. A HDM-induced murine allergic asthma model was also established. We estimated the power of sCD93 to predict allergic asthma in a retrospective post-hoc analysis containing 96 human samples. HDM-stimulated BEAS-2B cells showed increased mRNA expression levels of IL-6, IL-8, IL-33, TSLP, and CD93. The CD93 level in culture supernatants steadily increased for 24 h after allergen stimulation, which was significantly suppressed by both dexamethasone and CD93 silencing. CD93 silencing increased IL-6 and TSLP, but not IL-33 levels in culture supernatants. HDM-induced asthma mice showed significant airway hyperresponsiveness and inflammation with Th2 cytokine activation, along with decreased CD93 expression in bronchial epithelial cells and lung homogenates but increased serum CD93 levels. The sCD93 level in asthma patients was significantly higher than that in healthy controls and could predict asthma diagnosis with moderate sensitivity (71.4%) and specificity (82.4%) (AUC = 0.787, P < 0.001). The level of sCD93 which has potential role to predict asthma significantly increased after HDM stimulation via IL-6 and TSLP in vitro and in vivo. Asthma is a chronic inflammatory airway disease that is typically diagnosed based on a pulmonary function test with a bronchodilator and a bronchial provocation test 1. However, these tests require the effort and cooperation of the patient, which is often impossible owing to old age, deafness, misunderstanding, severe dyspnea, paroxysmal cough, and risk of an asthma attack 2. Therefore, there is a clinical need to identify a serum biomarker that can act as a non-invasive method of diagnosis for asthma patients; although several biomarkers have been suggested, they are not widely used in clinical settings owing to limited evidence 3,4. CD93 (C1qRp) is a transmembrane glycoprotein that is expressed on various cell types, including endothelial cells, epithelial cells, stem cells, platelets, and leukocytes 5,6. CD93 can be shed in a soluble form (sCD93) in response to inflammatory mediators, can be easily measured, and is considered to be associated with various inflammatory and immune associated diseases, including asthma 7,8. In addition, CD93 has angiogenic and growth-stimulating effects 9-11. Raedler et al. 12 showed that CD93 gene expression was significantly higher in non-allergic asthma patients than healthy controls, and Sigari et al. 13 demonstrated that the serum CD93 level increased under asthma exacerbation and decreased following proper treatment. We also previously reported the potential of sCD93 as a novel biomarker for asthma using an ovalbumin-induced asthma murine model and human patients 14,15. Howev...

Activation of the Complement and Coagulation Systems in the Small Airways in Asthma

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Soluble Complement Component 1q Receptor 1 (sCD93) Is Associated with Graft Function in Kidney Transplant Recipients

“…Increased expression of membrane CD93 was observed on activated macrophages along with increased concentrations of sCD93 in plasma [ 5 ]. Consequently, increased circulating sCD93 was observed in acute and chronic inflammatory conditions in human, including myocardial infarction [ 12 ], autoimmune [ 13 , 14 , 15 , 16 ] and allergic diseases [ 17 , 18 , 19 ].…”

Predictive Value of sCD93 in The Diagnosis of Bronchial Asthma

“…Also, these tests may not help to define the underlying airway inflammation. That's why recent asthma research is focusing on non-invasive and reliable cellular, soluble and genetic biomarkers 12 .…”