key: cord-0955012-bq43brcy
authors: Angileri, Francesca; Légaré, Sébastien; Marino Gammazza, Antonella; Conway de Macario, Everly; Macario, Alberto J. L.; Cappello, Francesco
title: Is molecular mimicry the culprit in the autoimmune haemolytic anaemia affecting patients with COVID‐19?
date: 2020-06-08
journal: Br J Haematol
DOI: 10.1111/bjh.16883
sha: 383fe945ba5a5ed1a8decae6c2360029d4a017ec
doc_id: 955012
cord_uid: bq43brcy

This Journal recently published two papers describing autoimmune hemolytic anemia (AIHA) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (1, 2). AIHA is characterized by the destruction of red cells by autoantibodies, but the mechanism underpinning autoimmunity in COVID-19 patients has yet to be elucidated.

The British Journal of Haematology recently published two papers describing autoimmune haemolytic anaemia (AIHA) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. 1,2 AIHA is characterised by the destruction of red cells by autoantibodies, but the mechanism underpinning autoimmunity in patients with coronavirus disease 2019 (COVID-19) has yet to be elucidated.

We recently postulated that molecular mimicry could be at the basis of the most severe complications observed in SARS-CoV-2-induced disease (COVID-19). 3, 4 For example, antibodies elicited against viral proteins could very well cross-react with vascular endothelial proteins if they shared antigenic epitopes. This would trigger extensive vasculitis followed by thrombosis and widespread intravascular coagulation with multi-organ failure. 5 Here, we would like to posit the hypothesis that molecular mimicry is also a determinant factor in AIHA in patients with COVID-19, with Ankyrin 1 (ANK-1) and the viral protein Spike being the central players.

ANK-1 is an erythrocyte membrane protein that is important for red cell differentiation and function, providing the primary connection between the membrane skeleton and the plasma membrane. 6 It is defective in patients with hereditary spherocytosis, a common cause of haemolytic anaemia. 6 We found that ANK-1 shares a putative immunogenicantigenic epitope (amino acids LLLQY) with 100% identity with the SARS-CoV-2 surface glycoprotein named Spike protein (Table I) . We established that this epitope is part of the Spike's predicted immunogenic epitope 750-SNLLLQYGSFCTQL-763 for B cells by using the immune epitope database and analysis resource [Immune Epitope Database (IEDB), https://www.iedb.org/]. This database contains experimentally validated epitopes and tools to predict epitopes recognisable be T and B cells and is used also in the design of vaccines. 7 With this Letter, we would like to call the attention of the scientific community to the structural similarity between ANK-1 and the viral protein Spike. We hope it will prompt further research aiming at determining if the potential immunological cross-reactivity between ANK-1 and Spike contributes to the pathogenesis of AIHA in patients with COVID-19. Information on this topic may open new avenues toward designing efficacious therapies.

Simultaneous onset of COVID-19 and autoimmune haemolytic anaemia

Autoimmune haemolytic anaemia associated with Covid-19 infection

Is COVID-19 a proteiform disease inducing also molecular mimicry phenomena?

COVID-19 and molecular mimicry: The Columbus' egg?

Molecular mimicry may explain multi-organ damage in COVID-19

Structure and organization of the human ankyrin-1 gene. Basis for complexity of pre-mRNA processing

The immune epitope database (IEDB) 3.0