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

Douglas B. Kell*, Etheresia Pretorius*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

22 Downloads (Pure)

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.
Original languageEnglish
JournalBiochemical Journal
Volume480
Issue number15
Pages (from-to)1217-1240
ISSN0264-6021
DOIs
Publication statusPublished - 2023

Fingerprint

Dive into the research topics of 'Are fibrinaloid microclots a cause of autoimmunity in Long Covid and other post-infection diseases?'. Together they form a unique fingerprint.

Cite this