Dataset Information

Posttranslational forms of beta 2-glycoprotein I in the pathogenesis of the antiphospholipid syndrome.

ABSTRACT: The antiphospholipid syndrome (APS) is an autoimmune disease characterised by a procoagulant state that predisposes to recurrent thrombosis and miscarriages. Two major discoveries have advanced our understanding of the underlying complex pathogenesis of the APS. The first was the discovery that beta-2 glycoprotein-1 (?2GPI) is the major auto antigen in APS. The second was the discovery in more recent years that ?2GPI contains allosteric disulphide bonds susceptible to posttranslational modification that may be involved in the development of autoantibodies in APS. The main allosteric disulphide bond in the fifth domain of ?2GPI can exist in two redox states: free thiol or oxidised. It is the conformational transformation of ?2GPI from its free thiol form to its more immunogenic oxidised form that exposes neo-epitopes on the first and fifth domains. The purpose of this review is to highlight the recent findings on the posttranslational forms of ?2GPI in the pathogenesis of APS. We suggest that novel assays quantitating the different redox forms of ?2GPI in plasma or serum may be used to supplement existing clinical and laboratory assays to more accurately stratify risk of thrombosis or miscarriage in APS patients.

SUBMITTER: El-Assaad F

PROVIDER: S-EPMC5056467 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Posttranslational forms of beta 2-glycoprotein I in the pathogenesis of the antiphospholipid syndrome.

El-Assaad Fatima F Krilis Steven A SA Giannakopoulos Bill B

Thrombosis journal 20161004 Suppl 1

The antiphospholipid syndrome (APS) is an autoimmune disease characterised by a procoagulant state that predisposes to recurrent thrombosis and miscarriages. Two major discoveries have advanced our understanding of the underlying complex pathogenesis of the APS. The first was the discovery that beta-2 glycoprotein-1 (β2GPI) is the major auto antigen in APS. The second was the discovery in more recent years that β2GPI contains allosteric disulphide bonds susceptible to posttranslational modificat ...[more]

PMID: 27766046

Similar Datasets

Project description:ObjectivePatients with coronavirus disease 2019 (COVID-19) present coagulation abnormalities and thromboembolic events that resemble antiphospholipid syndrome (APS). This work has aimed to study the prevalence of APS-related antigens, antibodies, and immune complexes in patients with COVID-19 and their association with clinical events.MethodsA prospective study was conducted on 474 adults with severe acute respiratory syndrome coronavirus 2 infection hospitalized in two Spanish university hospitals. Patients were evaluated for classic and extra-criteria antiphospholipid antibodies (aPLs), immunoglobulin G (IgG)/immunoglobulin M (IgM) anticardiolipin, IgG/IgM/immunoglobulin A (IgA) anti-β2-glicoprotein-I (aβ2GPI), IgG/IgM antiphosphatidylserine/prothrombin (aPS/PT), the immune complex of IgA aβ2GPI (IgA-aβ2GPI), bounded to β2-glicoprotein-1 (β2GPI) and β2GPI levels soon after COVID-19 diagnosis and were followed-up until medical discharge or death.ResultsPrevalence of aPLs in patients with COVID-19 was as follows: classic aPLs, 5.8%; aPS/PT, 4.6%; IgA-aβ2GPI, 15%; and any aPL, 21%. When patients were compared with individuals of a control group of a similar age, the only significant difference found was the higher prevalence of IgA-aβ2GPI (odds ratio: 2.31; 95% confidence interval: 1.16-4.09). No significant differences were observed in survival, thrombosis, or ventilatory failure in aPL-positive versus aPL-negative patients. β2GPI median levels were much lower in patients with COVID-19 (15.9 mg/l) than in blood donors (168.8 mg/l; P < 0.001). Only 3.5% of patients with COVID-19 had normal levels of β2GPI (>85 mg/l). Low levels of β2GPI were significantly associated with ventilatory failure (P = 0.026).Conclusionβ2GPI levels were much lower in patients with COVID-19 than in healthy people. Low β2GPI-levels were associated with ventilatory failure. No differences were observed in the COVID-19 evolution between aPL-positive and aPL-negative patients. Functional β2GPI deficiency could trigger a clinical process similar to that seen in APS but in the absence of aPLs.

Dataset Information

Posttranslational forms of beta 2-glycoprotein I in the pathogenesis of the antiphospholipid syndrome.

Publications

Posttranslational forms of beta 2-glycoprotein I in the pathogenesis of the antiphospholipid syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets