Autoantibodies to heat shock protein 60, 70, and 90 are not altered in the anti-SARS-CoV-2 IgG-seropositive humans without or with mild symptoms

Abstract

Highly conserved heat shock proteins (Hsps) are localized in the cytoplasm and cellular organelles, and act as molecular chaperones or proteases. Members of Hsp families are released into the extracellular milieu under both normal and stress conditions. It is hypothesized that the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) has the potential to elicit autoimmunity due to molecular mimicry between human extracellular Hsps and immunogenic proteins of the virus. To confirm the above hypothesis, levels of circulating autoantibodies directed to the key human chaperones i.e., Hsp60, Hsp70, and Hsp90 in the anti-SARS-CoV-2 IgG-seropositive participants have been evaluated. Twenty-six healthy volunteers who got two doses of the mRNA vaccine encoding the viral spike protein, anti-SARS-CoV-2 IgG-positive participants (n = 15), and healthy naïve (anti-SARS-CoV-2 IgG-negative) volunteers (n = 51) have been included in this study. We found that the serum levels of anti-Hsp60, anti-Hsp70, and anti-Hsp90 autoantibodies of the IgG, IgM, or IgA isotype remained unchanged in either the anti-COVID-19-immunized humans or the anti-SARS-CoV-2 IgG-positive participants when compared to healthy naïve volunteers, as measured by enzyme-linked immunosorbent assay. Our results showing that the humoral immune response to SARS-CoV-2 did not include the production of anti-SARS-CoV-2 antibodies that also recognized extracellular heat shock protein 60, 70, and 90 represent a partial evaluation of the autoimmunity hypothesis stated above. Further testing for cell-based immunity will be necessary to fully evaluate this hypothesis.

Case Report: Circulating Anti-SARS-CoV-2 Antibodies Do Not Cross-React With Pemphigus or Pemphigoid Autoantigens

“…These results together with a recent related report on heat shock protein autoantibodies argue against a relationship between SARS-CoV-2 infection/vaccines and AIBDs with respect to disease-triggering antibody cross-reactivity, as previously hypothesized (1,6). Our findings also encourage COVID-19 vaccination in patients with AIBDs, as previously recommended (7).…”

“…Twelve post-COVID-19 individuals and 12 healthy volunteers immunized with two doses of the mRNA COVID-19 vaccine from Pfizer-BioNTech, who were all part of a previous study cohort reported by Mantej et al (6), have been included in this investigation (Table 1). Serum samples of these blood donors were tested for autoantibodies to desmoglein 1, desmoglein 3, envoplakin, BP180, BP230, and type VII collagen.…”

COVID ‐19 and autoimmune phenomena: Vitiligo after Astrazeneca vaccine

“…However, IgG antibodies generated against SARS‐CoV‐2 have not been shown to be able to recognize and react against heat shock proteins. 12 …”

“…However, IgG antibodies generated against SARS-CoV-2 have not been shown to be able to recognize and react against heat shock proteins. 12 Another possible mechanism suggested by Abdullah et al 13 posits that COVID-19 infection would stimulate dendritic cells to produce massive amounts of IFN-I, which also plays an important role in the pathogenesis of vitiligo. In the case of psoriatic flare-up reactions, it has been suggested that the mRNA vaccines may cause a significant increase in IL-6 production and recruitment of Th17 cells, 6 which not only participate in the pathogenesis of psoriasis, but also in many other autoimmune diseases.…”

Risk surveillance and mitigation: autoantibodies as triggers and inhibitors of severe reactions to SARS-CoV-2 infection

“…However, a study conducted by Mantej et al . ( 2021 ) showed no significant difference in anti-HSP60, anti-HSP70, and anti-HSP90 auto-Ab levels in serum of SARS-CoV-2 seropositive patients, seropositive mRNA vaccinated individuals, and seronegative healthy individuals (Mantej et al 2021 ). Collectively these findings suggest that auto-Abs are important in COVID-19-related neurological disorders.…”