Pilot study for immunoglobulin E as a prognostic biomarker in coronavirus disease 2019.

BACKGROUND: Laboratory biomarkers to estimate the severity of coronavirus disease 2019 (COVID-19) are crucial during the pandemic since resource allocation must be carefully planned. AIMS: To evaluate the effects of basal serum total immunoglobulin E (IgE) levels and changes in inflammatory parameters on the clinical progression of patients hospitalised with COVID-19. METHODS: Patients hospitalised with confirmed COVID-19 were included in the study. Laboratory data and total IgE levels were measured on admission. Lymphocyte, eosinophil, ferritin, d-dimer and C-reactive protein parameters were recorded at baseline and on the 3rd and 14th days of hospitalisation. RESULTS: The study enrolled 202 patients, of which 102 (50.5%) were males. The average age was 50.17 ± 19.68 years. Of the COVID-19 patients, 41 (20.3%) showed clinical progression. Serum total IgE concentrations were markedly higher (172.90 (0-2124) vs 38.70 (0-912); P < 0.001) and serum eosinophil levels were significantly lower (0.015 (0-1.200) vs 0.040 (0-1.360); P = 0.002) in clinically worsened COVID-19 patients when compared with stable patients. The optimal cut-off for predicting clinical worsening was 105.2 ng/L, with 61% sensitivity, 82% specificity, 46.3% positive predictive value and 89.2% negative predictive value (area under the curve = 0.729). Multivariable analysis to define risk factors for disease progression identified higher total IgE and C-reactive protein levels as independent predictors. CONCLUSIONS: Our single-centre pilot study determined that total IgE levels may be a negative prognostic factor for clinical progression in patients hospitalised due to COVID-19 infection. Future studies are required to determine the impact of individuals' underlying immune predispositions on outcomes of COVID-19 infections.

Defective expression of polarity protein Par3 promotes cervical tumorigenesis and metastasis.

OBJECTIVES: The aim of this study was to investigate whether the partition-defective 3 protein (Par3) regulates cervical carcinoma growth and metastasis. MATERIALS AND METHODS: Immunohistochemistry (IHC) was used to analyze the expression of Par3 protein in samples from 89 cervical squamous cell carcinoma (CSCC) patients among Uyghur women. The specific short hairpin (shRNA) vector as well as eu- karyotic expression vector of PARD3 was transfected into SiHa cell lines. The variation of migration and invasion after transfection was determined using Transwell assays, cell cycle, and apoptosis were assayed by flow cytometry, respectively. RESULTS: The incidence of CSCC was associated with reduced expression of Par3. Downregulation of Par3 was significantly associated with more advanced tumors (i.e., higher histological grade, lymph node involvement, and higher tumor stages) (p < 0.05 for all). Lost expression of Par3 promotes prolif- eration, inhibits apoptosis, and enhances migration and invasion. Loss of Par3 induces MMP9 expression and epithelial to mesenchymal transition (EMT) related genes (N-cadherin, E-cadherin, and ß-catenin) expression changed in SiHa cells. CONCLUSIONS: The reduced Par3 expression in cervical cancer indicates tumor-suppressive properties of Par3 that may be a marker of poor prognosis in cervical cancer patients, and the molecular determinants of epithelial polarity which have tumorigenesis enhancing impact, might through EMT.

Abrogation of lung inflammation in sensitized Stat6-deficient mice is dependent on the allergen inhalation procedure.

Conflicting results have been reported about the role of Stat6 in allergen-induced airway inflammation. We have studied the influence of the allergen inhalation procedure on the inflammatory response using wild-type and Stat6-deficient mice generated on a C57BL/6 background. Animals were immunized i.p. on day 0 and 7 with ovalbumin (OVA) and then received aerosolized OVA or phosphate buffer saline challenge (acute on day 14; chronic on day 14, 15, 16, 17 and 18) before being sacrificed at different time points. Following an acute challenge, Stat6-deficiency fully abrogated the increase in serum IgE levels and the development of lung inflammation (inflammatory cell infiltration, IL-4 and IL-5 release, and increase in plasma leakage). Following chronic challenge, despite the absence of IgE, IL-4 and IL-5, Stat6-deficient mice develop a characteristic lung inflammation, although the intensity was smaller when compared with the wild-type mice. OVA-induced early bronchoconstriction was observed in wild-type mice only after chronic challenge, and this was totally abrogated in the Stat6-deficient animals. These results suggest that Stat6 signalling is essential for the development of allergic airway inflammation following an acute allergen exposure. However, in a more chronic situation, the airway inflammatory response seems to be only partially mediated by Stat6.