Abstract
Immune homeostasis is disturbed during severe viral infections, which can lead to loss of tolerance to self-peptides and result in short- or long-term autoimmunity. Using publicly available transcriptomic datasets, we conducted an in-silico analyses to evaluate the expression levels of 52 autoantigens, known to be associated with 24 autoimmune diseases, during SAR-CoV-2 infection. Seven autoantigens (MPO, PRTN3, PADI4, IFIH1, TRIM21, PTPRN2, and TSHR) were upregulated in whole blood samples. MPO and TSHR were overexpressed in both lung autopsies and whole blood tissue and were associated with more severe COVID-19. Neutrophil activation derived autoantigens (MPO, PRTN3, and PADI4) were prominently increased in blood of both SARS-CoV-1 and SARS-CoV-2 viral infections, while TSHR and PTPRN2 autoantigens were specifically increased in SARS-CoV-2. Using single-cell dataset from peripheral blood mononuclear cells (PBMCs), we observed an upregulation of MPO, PRTN3, and PADI4 autoantigens within the low-density neutrophil subset. To validate our in-silico analysis, we measured plasma protein levels of two autoantigens, MPO and PRTN3, in severe and asymptomatic COVID-19. The protein levels of these two autoantigens were significantly upregulated in more severe COVID-19 infections. In conclusion, the immunopathology and severity of COVID-19 could result in transient autoimmune activation. Longitudinal follow-up studies of confirmed cases of COVID-19 could determine the enduring effects of viral infection including development of autoimmune disease.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), appeared first in Wuhan, China, in December 2019 and has since rapidly spread globally [1, 2]
RNA-sequencing data was extracted from 10 controls, mild COVID-19, severe COVID-19 (Figures 1B, C)
Seven autoantigens were upregulated in blood of severe COVID-19 patients (MPO, PRTN3, PADI4, IFIH1, TRIM21, PTPRN2, and TSHR) (Figure 1B), while four autoantigens (MPO, PRTN3, IFIH1, and PADI4) were increased in blood of mild patients (Figure 1C)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), appeared first in Wuhan, China, in December 2019 and has since rapidly spread globally [1, 2]. Multiple factors are involved in the development of autoimmunity, including genetics, age, and environment [11]. Viral infections, those resulting in low interferon production, as it is the case with SARS-CoV-2 infection, have long been associated with induction of autoimmunity [11]. Similar to many severe viral infections, SARS-CoV-2 could trigger the autoimmune reaction through multiple mechanism including molecular mimicry, epitope spreading, bystander activation, and persistence of latent virus [12,13,14,15]. Development of crossreactive epitopes are dependent on viral strain as well as host genetic susceptibility, including human leucocyte antigen (HLA) polymorphism
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