Dataset Information

MASPs at the crossroad between the complement and the coagulation cascades - the case for COVID-19.

ABSTRACT: Components of the complement system and atypical parameters of coagulation were reported in COVID-19 patients, as well as the exacerbation of the inflammation and coagulation activity. Mannose binding lectin (MBL)- associated serine proteases (MASPs) play an important role in viral recognition and subsequent activation of the lectin pathway of the complement system and blood coagulation, connecting both processes. Genetic variants of MASP1 and MASP2 genes are further associated with different levels and functional efficiency of their encoded proteins, modulating susceptibility and severity to diseases. Our review highlights the possible role of MASPs in SARS-COV-2 binding and activation of the lectin pathway and blood coagulation cascades, as well as their associations with comorbidities of COVID-19. MASP-1 and/or MASP-2 present an increased expression in patients with COVID-19 risk factors: diabetes, arterial hypertension and cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, and cerebrovascular disease. Based also on the positive results of COVID-19 patients with anti-MASP-2 antibody, we propose the use of MASPs as a possible biomarker of the progression of COVID-19 and the investigation of new treatment strategies taking into consideration the dual role of MASPs, including MASP inhibitors as promising therapeutic targets against COVID-19.

SUBMITTER: Bumiller-Bini V

PROVIDER: S-EPMC7982787 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MASPs at the crossroad between the complement and the coagulation cascades - the case for COVID-19.

Bumiller-Bini Valéria V de Freitas Oliveira-Toré Camila C Carvalho Tamyres Mingorance TM Kretzschmar Gabriela Canalli GC Gonçalves Letícia Boslooper LB Alencar Nina de Moura NM Gasparetto Filho Miguel Angelo MA Beltrame Marcia Holsbach MH Winter Boldt Angelica Beate AB

Genetics and molecular biology 20210317 1 Suppl 1

Components of the complement system and atypical parameters of coagulation were reported in COVID-19 patients, as well as the exacerbation of the inflammation and coagulation activity. Mannose binding lectin (MBL)- associated serine proteases (MASPs) play an important role in viral recognition and subsequent activation of the lectin pathway of the complement system and blood coagulation, connecting both processes. Genetic variants of MASP1 and MASP2 genes are further associated with different le ...[more]

PMID: 33729332

Similar Datasets

Project description:BackgroundImmune checkpoint inhibitors (ICIs) have shown efficacy in patients with metastatic urothelial cancer (mUC), however, only a small subset of patients could benefit from ICIs. Identifying predictive biomarkers of ICIs in patients with mUC is clinical meaningful for patient stratification and administration.MethodsClinical and transcriptomic data of mUC patients treated with ICIs from mUC cohort (IMvigor210 study) was utilized to explore the predictive biomarkers. LASSO Cox regression was performed to construct a predictive model. The predictive model was trained and tested in the mUC cohort, and then exploratively tested in clear cell renal cell carcinoma (ccRCC) and melanoma cohorts in which patients also received ICIs regimens.ResultsThe differentially expressed genes (DEGs) in complement and coagulation cascades pathway (CCCP) were mainly enriched in non-responders of ICIs in the mUC cohort. A CCCP risk score was constructed based on the DEGs in CCCP. Patients with a low-risk score were more responsive to ICIs and had better overall survival (OS) than those with a high-risk score in the training set (HR, 0.38; 95%CI, 0.27-0.53, P<0.001) and the test set (HR, 0.34; 95%CI, 0.17-0.71, P=0.003). The association between the CCCP risk score and OS remained significant in the multivariable cox regression by adjusting PD-L1 expression and TMB (P<0.05). In addition, there was no difference for OS in the bladder cancer patients without ICIs (TCGA-BLCA cohort, HR, 0.76, 95%CI, 0.49-1.18, P=0.22), suggesting a predictive but not prognostic effect of the risk score. For the exploratory analysis, consistent results were observed that low-risk group showed superior OS in ccRCC cohort (HR, 0.52, 95%CI, 0.37-0.75, P<0.001) and melanoma cohort (HR, 0.27, 95%CI, 0.12-0.62, P=0.001).ConclusionsOur study showed that the CCCP risk score is an independent biomarker that predicts the efficacy of ICIs in mUC patients. The patients with a low-risk score tend to have a better response to ICIs and a longer life time probably due to the immune-activated TME. Further studies are needed to validate the clinical utility of the seven-gene signature.

Project description:ObjectivesThe objective of this study was to compare plasma proteomes of patients with confirmed fracture-related infections (FRIs) matched to noninfected controls using liquid chromatography-mass spectrometry.MethodsDesignThis was a prospective case-control study.SettingThe study was conducted at a single, academic, Level 1 trauma center.Patient selection criteriaPatients meeting confirmatory FRI criteria were matched to controls without infection based on fracture region, age, and time after surgery from June 2019 to January 2022. Tandem mass tag liquid chromatography-mass spectrometry analysis of patient plasma samples was performed.Outcome measures and comparisonsProtein abundance ratios in plasma for patients with FRI compared with those for matched controls without infection were calculated.ResultsTwenty-seven patients meeting confirmatory FRI criteria were matched to 27 controls. Abundance ratios for more than 1000 proteins were measured in the 54 plasma samples. Seventy-three proteins were found to be increased or decreased in patients with FRI compared with those in matched controls (unadjusted t test P < 0.05). Thirty-two of these proteins were found in all 54 patient samples and underwent subsequent principal component analysis to reduce the dimensionality of the large proteomics dataset. A 3-component principal component analysis accounted for 45.7% of the variation in the dataset and had 88.9% specificity for the diagnosis of FRI. STRING protein-protein interaction network analysis of these 3 PCs revealed activation of the complement and coagulation cascades through the Reactome pathway database (false discovery rates <0.05).ConclusionsProteomic analyses of plasma from patients with FRI demonstrate systemic activation of the complement and coagulation cascades. Further investigation along these lines may help to better understand the systemic response to FRI and improve diagnostic strategies using proteomics.Level of evidencePrognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Dataset Information

MASPs at the crossroad between the complement and the coagulation cascades - the case for COVID-19.

Publications

MASPs at the crossroad between the complement and the coagulation cascades - the case for COVID-19.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets