Predicted B Cell Epitopes Highlight the Potential for COVID-19 to Drive Self-Reactive Immunity

Abstract

COVID-19, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), whilst commonly characterised as a respiratory disease, is reported to have extrapulmonary manifestations in multiple organs. Extrapulmonary involvement in COVID-19 includes autoimmune-like diseases such as Guillain-Barré syndrome and Kawasaki disease, as well as the presence of various autoantibodies including those associated with autoimmune diseases such a systemic lupus erythematosus (e.g. ANA, anti-La). Multiple strains of SARS-CoV-2 have emerged globally, some of which are found to be associated with increased transmissibility and severe disease. We performed an unbiased comprehensive mapping of the potential for cross-reactivity with self-antigens across multiple SARS-CoV-2 proteins and compared identified immunogenic regions across multiples strains. Using the Immune Epitope Database (IEDB) B cell epitope prediction tool, regions predicted as antibody epitopes with high prediction scores were selected. Epitope sequences were then blasted to eight other global strains to identify mutations within these regions. Of the 15 sequences compared, eight had a mutation in at least one other global strain. Predicted epitopes were then compared to human proteins using the NCBI blast tool. In contrast to studies focusing on short sequences of peptide identity, we have taken an immunological approach to selection criteria for further analysis and have identified 136 alignments of 6–23 amino acids (aa) in 129 human proteins that are immunologically likely to be cross-reactive with SARS-CoV-2. Additionally, to identify regions with significant potential to interfere with host cell function-or promote immunopathology, we identified epitope regions more likely to be accessible to pathogenic autoantibodies in the host, selected using a novel combination of sequence similarity, and modelling protein and alignment localization with a focus on extracellular regions. Our analysis identified 11 new predicted B-cell epitopes in host proteins, potentially capable of explaining key aspects of COVID-19 extrapulmonary pathology, and which were missed in other in silico studies which used direct identity rather than immunologically related functional criteria.

The rise and spread of the SARS-CoV-2 AY.122 lineage in Russia

“…Site ORF7a:45 experiences episodic diversifying selection (according to MEME algorithm of HyPhy) and increase of non-reference amino acid in frequency according to ( https://observablehq.com/@spond/evolutionary-annotation-of-sars-cov-2-covid-19-genomes-enab?collection=@spond/sars-cov-2 ). It has also been predicted to be included in the B-cell epitope [ 43 ].…”

Autoantibodies in COVID‐19 correlate with antiviral humoral responses and distinct immune signatures

“…Autoantibody production could result from the activation of autoreactive B and T cells recognizing viral epitopes by means of molecular mimicry. 30 , 31 Alternatively, antigen‐independent ‘bystander’ activation of autoreactive B and T cells by cytokines and other inflammatory mediators could drive autoantibody production. 32 , 33 Particularly in severe COVID‐19, which is associated with early neutrophilia and pronounced neutrophil extracellular trap (NET) formation, 34 , 35 NETs expose shielded intracellular self‐antigens, 25 , 36 , 37 thus causing the production of ANCA and ANA.…”

The rise and spread of the SARS-CoV-2 AY.122 lineage in Russia

“…Site ORF7a:45 experiences episodic diversifying selection (according to MEME algorithm of HyPhy) and increase of non-reference amino acid in frequency according to ( https://observablehq.com/@spond/evolutionary-annotation-of-sars-cov-2-covid-19-genomes-enab?collection=@spond/sars-cov-2 ). It has also been predicted to be included in the B-cell epitope ( Moody et al. 2021 ).…”