SARS-CoV-2 and Guillain-Barré syndrome: molecular mimicry with human heat shock proteins as potential pathogenic mechanism

Abstract

Severe acute respiratory syndrome-related coronavirus 2 infection has been associated with Guillain-Barré syndrome. We investigated here the potential mechanism underlying the virus-induced damage of the peripheral nervous systems by searching the viral amino acid sequence for peptides common to human autoantigens associated with immune-mediated polyneuropathies. Our results show molecular mimicry between the virus and human heat shock proteins 90 and 60, which are associated with Guillain-Barré syndrome and other autoimmune diseases. Crucially, the shared peptides are embedded in immunoreactive epitopes that have been experimentally validated in the human host.

GM1 ganglioside antibody and COVID-19 related Guillain Barre Syndrome – A case report, systemic review and implication for vaccine development

“…ACE2 is present on neuron and glial cells [ 22 ]. Other candidate being mentioned is heat shock protein (HSP), in particular HSP 27, 60, 70 and 90 [ 23 ]. Identifying the true antigen related to COVID-19 induced GBS and MFS may be of paramount importance to improving the safety profile of these new vaccines.…”

Neuromuscular presentations in patients with COVID-19

“…SARS-CoV-2 shares two hexapeptides with human shock proteins 90 and 60. Both these proteins have immunogenic potentials, and they are among the 41 human proteins associated with Guillain-Barrè syndrome and chronic inflammatory demyelinating polyneuropathy [103]. The other neuropathies reported in patients with COVID-19 may also be secondary to immune-mediated mechanisms.…”

COVID-19-Associated Guillain-Barre Syndrome: Atypical Para-infectious Profile, Symptom Overlap, and Increased Risk of Severe Neurological Complications

“…1). The SARS-CoV-2 infection triggers an adaptive immune response in which T cell-B cell interactions result in the production of SARS-CoV-2specific antibodies [14], but a similarity in viral and ganglioside peptide sequences or structure (molecular mimicry) [15] can result in a loss of self-tolerance [16]. Under these circumstances, the gangliosides, which are predominantly located on the membranes of neurons and the Schwann cells [17], which form the myelin sheath, may act as receptors for antiganglioside antibodies, which neutralize the neurons' complement inhibitory activity [18] and turn them into targets for an autoimmune-mediated destruction of myelin sheaths or axons [16,19] (Fig.…”