Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins

Nunez-Castilla, Janelle; Stebliankin, Vitalii; Baral, Prabin; Balbin, Christian A.; Sobhan, Masrur; Cickovski, Trevor; Mondal, Ananda Mohan; Narasimhan, Giri; Chapagain, Prem P.; Mathee, Kalai; Siltberg-Liberles, Jessica

doi:10.3390/v14071415

Cited by 54 publications

(35 citation statements)

References 83 publications

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“…Particular attention has been paid to the spike protein of SARS‐CoV‐2 as it serves as a major antigen. As shown using the bioinformatic approaches, its motifs revealed molecular mimicry with various components of the cardiovascular system (e.g., cGMP‐dependent protein kinase 1, ephrin‐B2, thrombopoietin, and tropomyosin), immune system (e.g., tumor necrosis factor receptors, interleukin‐6 receptor), and nervous system (phosphacan, attractin, and teneurin‐4) 26–28 . However, the potential for such mimicry is much higher since, in addition to spike protein, the genome of SARS‐CoV‐2 encodes 3 other structural proteins, 16 nonstructural proteins (NSP), and 9 accessory proteins 29 .…”

Section: Introductionmentioning

confidence: 99%

“…As shown using the bioinformatic approaches, its motifs revealed molecular mimicry with various components of the cardiovascular system (e.g., cGMPdependent protein kinase 1, ephrin-B2, thrombopoietin, and tropomyosin), immune system (e.g., tumor necrosis factor receptors, interleukin-6 receptor), and nervous system (phosphacan, attractin, and teneurin-4). [26][27][28] However, the potential for such mimicry is much higher since, in addition to spike protein, the genome of SARS-CoV-2 encodes 3 other structural proteins, 16 nonstructural proteins (NSP), and 9 accessory proteins. 29 For example, one study found the homology between the viral open reading frames 1a and 1b, and between the multi-domain NSP3, and the human proteins: mono-ADP-ribosyltransferase, mono-ADP-ribosyl-transferase, and ADPribose glycohydrolase as well as between open reading frame 7b and the low-density lipoprotein receptor-related protein 2.…”

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confidence: 99%

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Overview of autoantibodies in COVID‐19 convalescents

Dobrowolska

Zarębska-Michaluk

Siller‐Matula

et al. 2023

Journal of Medical Virology

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Accumulating evidence shows that SARS‐CoV‐2 can potentially trigger autoimmune processes, which can be responsible for the long‐term consequences of COVID‐19. Therefore, this paper aims to review the autoantibodies reported in COVID‐19 convalescents. Six main groups were distinguished: (i) autoantibodies against components of the immune system, (ii) autoantibodies against components of the cardiovascular system, (iii) thyroid autoantibodies, (iv) autoantibodies specific for rheumatoid diseases, (v) antibodies against G‐protein coupled receptors, and (vi) other autoantibodies. The evidence reviewed here clearly highlights that SARS‐CoV‐2 infection may induce humoral autoimmune responses. However, the available studies share number of limitations, such as: (1) the sole presence of autoantibodies does not necessarily implicate the clinically‐relevant risks, (2) functional investigations were rarely performed and it is often unknown whether observed autoantibodies are pathogenic, (3) the control seroprevalence, in healthy, noninfected individuals was often not reported; thus it is sometimes unknown whether the detected autoantibodies are the result of SARS‐CoV‐2 infection or the accidental post‐COVID‐19 detection, (4) the presence of autoantibodies was rarely correlated with symptoms of the post‐COVID‐19 syndrome, (5) the size of the studied groups were often small, (6) the studies focused predominantly on adult populations, (7) age‐ and sex‐related differences in seroprevalence of autoantibodies were rarely explored, (8) genetic predispositions that may be involved in generation of autoantibodies during SARS‐CoV‐2 infections were not investigated, and (9) the autoimmune reactions following infection with SARS‐CoV‐2 variants that vary in the clinical course of infection remain unexplored. Further longitudinal studies are advocated to assess the link between identified autoantibodies and particular clinical outcomes in COVID‐19 convalescents.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Overview of autoantibodies in COVID‐19 convalescents

Dobrowolska

Zarębska-Michaluk

Siller‐Matula

et al. 2023

Journal of Medical Virology

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“…Kanduc and Shoenfeld 25 conducted a quantitative peptide sharing analysis, which demonstrated massive heptapeptide sharing between the SARS‐CoV‐2 SP and human proteins. The significant overlap between the SARS‐CoV‐2 SP and human proteins may be the connection that creates a mutual pathway between COVID‐19 infection, vaccination, and postinfection/vaccination autoimmune responses 26 …”

Section: Discussionmentioning

confidence: 99%

COVID‐19 vaccine–associated vitiligo: A cross‐sectional study in a tertiary referral center and systematic review

Tsai

2023

The Journal of Dermatology

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Vitiligo is an autoimmune skin disorder that occurs due to immunemediated loss of functional melanocytes, leading to patchy skin depigmentation. The triggering of an autoimmune phenomena in patients infected with coronavirus disease 2019 (COVID-19) and those receiving COVID-19 vaccinations has been increasingly reported, and these adverse events have also been seen in vitiligo. Cases of new-onset and exacerbation of vitiligo following COVID-19 vaccination have been reported in individuals of all ages, ethnicities, and with different vaccine types. While current guidelines and consensus recommend COVID-19 vaccination for most patients, including those with autoimmune diseases, 1,2 practitioners must assess the risk and potential for disease onset or flare-up. According to the Taiwan Centers for Disease Control, around 21.7 million people in our population have received at least one primary COVID-19 vaccine, with 94% of them having been vaccinated, while 88% have received at least two doses and 74% have received at least three doses. In light of the emergence of new Delta and Omicron variants, booster vaccination programs are now underway to enhance the humoral response. Some eligible groups can now receive the fourth vaccination booster and a fifth booster dose of Moderna's next-generation bivalent vaccine.Our study aims to report the incidence of vitiligo following primary and booster COVID-19 vaccines. We retrospectively reviewed electronic medical records of new-onset and exacerbations of vitiligo following COVID-19 vaccinations at our vitiligo clinic, which is located at a tertiary referral center. In addition, we conducted a systematic review to analyze the current evidence regarding COVID-19 vaccine-associated vitiligo. | MATERIAL S AND ME THODSWe conducted a retrospective study at our vitiligo clinic, which is located at a Taiwanese tertiary medical center (Chang Gung Memorial Hospital, Linkou, and Taipei branches). The study included patients with new-onset vitiligo or exacerbations of preexisting vitiligo that were diagnosed within a month of receiving COVID-19 vaccination between January 1, 2021, and September 30, 2022. We clinically diagnosed vitiligo based on the presence of acquired amelanotic macules and patches with well-defined margins and typical distribution. Wood's lamp examination was used to identify vitiligo lesions

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“…Hence, based on the current compendium of SARS-CoV-2-reactive TCRs (Bagaev et al, 2020), which may not be comprehensive, there was no evidence for viral persistence at the site of disease in our cohort. A more plausible hypothesis, given reports of cross-reactivity between SARS-CoV-2 and human antigens (Nunez-Castilla et al, 2022; Vojdani and Kharrazian, 2020), is that the PCLD TCR repertoire is directed against as yet unknown respiratory autoantigens. Identifying the antigenic targets of the PCLD T cell repertoire may present opportunities for more specific therapeutic interventions.…”

Section: Discussionmentioning

confidence: 99%

Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease

Mehta

Estrada

Denneny

et al. 2023

Preprint

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Rationale: Persistent pulmonary sequelae are evident in many survivors of acute coronavirus disease 2019 (COVID-19) but the molecular mechanisms responsible are incompletely understood. Post-COVID radiological lung abnormalities comprise two broad categories, organising pneumonia and reticulation, interpreted as indicative of subacute inflammation and fibrosis, respectively. Whether these two patterns represent distinct pathologies, likely to require different treatment strategies is not known. Objectives: We sought to identify differences at molecular and cellular level, in the local immunopathology of post-COVID inflammation and fibrosis. Methods: We compared single-cell transcriptomic profiles and T cell receptor (TCR) repertoires of bronchoalveolar cells obtained from convalescent individuals with each radiological pattern of post-COVID lung disease (PCLD). Measurements and Main Results: Inflammatory and fibrotic PCLD single-cell transcriptomes closely resembled each other across all cell types. However, CD4 central memory T cells (TCM) and CD8 effector memory T cells (TEM) were significantly more abundant in inflammatory PCLD. A greater proportion of CD4 TCM also exhibited clonal expansion in inflammatory PCLD. High levels of clustering of similar TCRs from multiple donors was a striking feature of both PCLD phenotypes, consistent with tissue localised antigen-specific immune responses, but there was no enrichment for known SARS-CoV-2 reactive TCRs. Conclusions: There is no evidence that radiographic organising pneumonia and reticulation in PCLD are associated with differential immmunopathological pathways. Inflammatory radiology is characterised by greater bronchoalveolar T cell accumulation. Both groups show evidence of shared antigen-specific T cell responses, but the antigenic target for these T cells remains to be identified.

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Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins

Cited by 54 publications

References 83 publications

Overview of autoantibodies in COVID‐19 convalescents

Overview of autoantibodies in COVID‐19 convalescents

COVID‐19 vaccine–associated vitiligo: A cross‐sectional study in a tertiary referral center and systematic review

Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease

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