ABSTRACT
COVID-19 is a highly selective disease in which SARS-CoV-2 infection can result in different clinical manifestations ranging from asymptomatic/mild to severe disease that requires hospitalization. In this study, we demonstrated that SARS-CoV-2 infection results in a glycosylation reprogramming of circulating lymphocytes at diagnosis. We identified a specific glycosignature of T cells, defined upon SARS-CoV-2 infection and apparently triggered by a serological factor. This specific glycan switch of T cells is detected at diagnosis being more pronounced in asymptomatic patients. We further demonstrated that asymptomatic patients display an increased expression of a viral-sensing receptor through the upregulation of DC-SIGN in monocytes. We showed that higher levels of DC-SIGN in monocytes at diagnosis correlates with better COVID-19 prognosis. This new evidence pave the way to the identification of a novel glycan-based response in T cells that may confer protection against SARS-CoV-2 infection in asymptomatic patients, highlighting a novel prognostic biomarker and potential therapeutic target.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Polysaccharides , Receptors, Virus , T-LymphocytesABSTRACT
Triple negative breast cancers (TNBCs) lack recurrent targetable driver mutations but demonstrate frequent copy number aberrations (CNAs). Here, we describe an integrative genomic and RNAi-based approach that identifies and validates gene addictions in TNBCs. CNAs and gene expression alterations are integrated and genes scored for pre-specified target features revealing 130 candidate genes. We test functional dependence on each of these genes using RNAi in breast cancer and non-malignant cells, validating malignant cell selective dependence upon 37 of 130 genes. Further analysis reveals a cluster of 13 TNBC addiction genes frequently co-upregulated that includes genes regulating cell cycle checkpoints, DNA damage response, and malignant cell selective mitotic genes. We validate the mechanism of addiction to a potential drug target: the mitotic kinesin family member C1 (KIFC1/HSET), essential for successful bipolar division of centrosome-amplified malignant cells and develop a potential selection biomarker to identify patients with tumors exhibiting centrosome amplification.
Subject(s)
Genomics/methods , Triple Negative Breast Neoplasms/genetics , Cell Cycle Checkpoints/genetics , DNA Copy Number Variations/genetics , DNA Damage/genetics , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/genetics , Gene Silencing/physiology , Humans , Kinesins/genetics , RNA InterferenceABSTRACT
Honey allergy is a very rare, but serious health condition. In this study, we presented 1 patient who had anaphylaxis after the honey allergological investigation with skin prick-prick test with honey. Honey as a food has been associated to allergic reactions and as the increased consumption of honey in health food may increase the incidence of honey-related allergic reactions.
