Are fibrinaloid microclots a cause of autoimmunity in Long Covid and other post-infection diseases?

Kell, Douglas B ORCID: 0000-0001-5838-7963 and Pretorius, Etheresia (2023) Are fibrinaloid microclots a cause of autoimmunity in Long Covid and other post-infection diseases? BIOCHEMICAL JOURNAL, 480 (15). pp. 1217-1240.

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Official URL: http://dx.doi.org/10.1042/bcj20230241

Abstract

It is now well established that the blood-clotting protein fibrinogen can polymerise into an anomalous form of fibrin that is amyloid in character; the resultant clots and microclots entrap many other molecules, stain with fluorogenic amyloid stains, are rather resistant to fibrinolysis, can block up microcapillaries, are implicated in a variety of diseases including Long COVID, and have been referred to as fibrinaloids. A necessary corollary of this anomalous polymerisation is the generation of novel epitopes in proteins that would normally be seen as 'self', and otherwise immunologically silent. The precise conformation of the resulting fibrinaloid clots (that, as with prions and classical amyloid proteins, can adopt multiple, stable conformations) must depend on the existing small molecules and metal ions that the fibrinogen may (and is some cases is known to) have bound before polymerisation. Any such novel epitopes, however, are likely to lead to the generation of autoantibodies. A convergent phenomenology, including distinct conformations and seeding of the anomalous form for initiation and propagation, is emerging to link knowledge in prions, prionoids, amyloids and now fibrinaloids. We here summarise the evidence for the above reasoning, which has substantial implications for our understanding of the genesis of autoimmunity (and the possible prevention thereof) based on the primary process of fibrinaloid formation.

Item Type:	Article
Uncontrolled Keywords:	Humans, Thrombosis, Amyloid, Fibrinogen, Prions, Autoimmunity, Amyloidogenic Proteins, COVID-19, Post-Acute COVID-19 Syndrome
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	02 Oct 2023 09:23
Last Modified:	02 Oct 2023 09:23
DOI:	10.1042/BCJ20230241
Open Access URL:	https://doi.org/10.1042/BCJ20230241
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3173272