The role of beta-2-glycoprotein I in health and disease associating structure with function: More than just APS

McDonnell, Thomas; Wincup, Chris; Buchholz, Ina; Pericleous, Charis; Giles, Ian; Ripoll, Vera M.; Cohen, Hannah; Delcea, Mihaela; Rahman, Anisur

doi:10.1016/j.blre.2019.100610

Cited by 101 publications

(151 citation statements)

References 208 publications

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“…It furthermore is associated with autoimmunity [167] and has anti-bacterial effects [168,169]. The diverse function of β2GPI, including its dual capability to up-and down-regulate the complement and coagulation systems depending upon external stimulus [170] may reflect hitherto unrecognised structural modifications via post-translational deimination, and be related to glycolysis [167].…”

Section: Discussionmentioning

confidence: 99%

Protein Deimination and Extracellular Vesicle Profiles in Antarctic Seabirds

Phillips

Kraev

Lange

2020

Biology

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Pelagic seabirds are amongst the most threatened of all avian groups. They face a range of immunological challenges which seem destined to increase due to environmental changes in their breeding and foraging habitats, affecting prey resources and exposure to pollution and pathogens. Therefore, the identification of biomarkers for the assessment of their health status is of considerable importance. Peptidylarginine deiminases (PADs) post-translationally convert arginine into citrulline in target proteins in an irreversible manner. PAD-mediated deimination can cause structural and functional changes in target proteins, allowing for protein moonlighting in physiological and pathophysiological processes. PADs furthermore contribute to the release of extracellular vesicles (EVs), which play important roles in cellular communication. In the present study, post-translationally deiminated protein and EV profiles of plasma were assessed in eight seabird species from the Antarctic, representing two avian orders: Procellariiformes (albatrosses and petrels) and Charadriiformes (waders, auks, gulls and skuas). We report some differences between the species assessed, with the narrowest EV profiles of 50–200 nm in the northern giant petrel Macronectes halli, and the highest abundance of larger 250–500 nm EVs in the brown skua Stercorarius antarcticus. The seabird EVs were positive for phylogenetically conserved EV markers and showed characteristic EV morphology. Post-translational deimination was identified in a range of key plasma proteins critical for immune response and metabolic pathways in three of the bird species under study; the wandering albatross Diomedea exulans, south polar skua Stercorarius maccormicki and northern giant petrel. Some differences in Gene Ontology (GO) biological and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for deiminated proteins were observed between these three species. This indicates that target proteins for deimination may differ, potentially contributing to a range of physiological functions relating to metabolism and immune response, as well as to key defence mechanisms. PAD protein homologues were identified in the seabird plasma by Western blotting via cross-reaction with human PAD antibodies, at an expected 75 kDa size. This is the first study to profile EVs and to identify deiminated proteins as putative novel plasma biomarkers in Antarctic seabirds. These biomarkers may be further refined to become useful indicators of physiological and immunological status in seabirds—many of which are globally threatened.

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Section: Discussionmentioning

confidence: 99%

Protein Deimination and Extracellular Vesicle Profiles in Antarctic Seabirds

Phillips

Kraev

Lange

2020

Biology

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“…Of note, increased levels of AMBP, B2M and LYZ have been associated with death in chronic kidney disease 39 . Levels of CFD and APOH, both involved in the complement system, were also increased 41,76 . CFD is eliminated renally and accumulates in end stage renal disease, possibly leading to enhanced complement activation via the alternative pathway 77 .…”

Section: Supplementary Note 1 Diagnostic Parameters and Proteome Sigmentioning

confidence: 96%

A time-resolved proteomic and diagnostic map characterizes COVID-19 disease progression and predicts outcome

Demichev¹,

Tober‐Lau²,

Nazarenko³

et al. 2020

Preprint

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COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. There is an urgent need for predictive markers that can guide clinical decision-making, inform about the effect of experimental therapies, and point to novel therapeutic targets. Here, we characterize the time-dependent progression of COVID-19 through different stages of the disease, by measuring 86 accredited diagnostic parameters and plasma proteomes at 687 sampling points, in a cohort of 139 patients during hospitalization. We report that the time-resolved patient molecular phenotypes reflect an initial spike in the systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution and immunomodulation. Further, we show that the early host response is predictive for the disease trajectory and gives rise to proteomic and diagnostic marker signatures that classify the need for supplemental oxygen therapy and mechanical ventilation, and that predict the time to recovery of mildly ill patients. In severely ill patients, the molecular phenotype of the early host response predicts survival, in two independent cohorts and weeks before outcome. We also identify age-specific molecular response to COVID-19, which involves increased inflammation and lipoprotein dysregulation in older patients. Our study provides a deep and time resolved molecular characterization of COVID-19 disease progression, and reports biomarkers for risk-adapted treatment strategies and molecular disease monitoring. Our study demonstrates accurate prognosis of COVID-19 outcome from proteomic signatures recorded weeks earlier.

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“…Over the next few years, the test method evolved so that fetal cow serum or adult bovine serum replaced gelatin/PBS as a sample diluent to provide sufficient β 2 GPI for a valid test, enzyme-labeled antihuman IgG or IgM antibodies replaced radiolabeled antihuman IgG or IgM antibodies, and ACA enzyme-linked immunosorbent assay (ELISA) was established [3]. ACA from patients with APS requires β 2 GPI as a cofactor for cardiolipin binding [4]. Thus, ACA assays may indirectly be dependent on the function and structure of β 2 GPI.…”

Section: Clinical Laboratory Detection Assaymentioning

confidence: 99%

Advances in the Research on Anticardiolipin Antibody

Wang

Zhang

et al. 2019

Journal of Immunology Research

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Anticardiolipin antibody (ACA) is a kind of autoantibody and is one of the antiphospholipid antibodies (aPLs). Phospholipids with a negative charge on platelets and endothelial cell membranes are ACA target antigens. ACA is common in systemic lupus erythematosus and other autoimmune diseases and is closely associated with thrombosis, thrombocytopenia, and spontaneous abortion. In 1983, Harris established a method for detecting ACA, and research on the antibody has gained worldwide attention and has developed rapidly. For this review, we browsed articles that cover most of the ACA-related studies in the last 25 years and extracted influential ideas and conclusions in this field.

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The role of beta-2-glycoprotein I in health and disease associating structure with function: More than just APS

Cited by 101 publications

References 208 publications

Protein Deimination and Extracellular Vesicle Profiles in Antarctic Seabirds

Protein Deimination and Extracellular Vesicle Profiles in Antarctic Seabirds

A time-resolved proteomic and diagnostic map characterizes COVID-19 disease progression and predicts outcome

Advances in the Research on Anticardiolipin Antibody

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