ABSTRACT
Both COVID-19 and autoimmune bullous diseases represent potentially life-threatening conditions. Autoimmunity has been a special focus during the COVID-19 pandemic considering the possible detrimental mutual influence between COVID-19 and autoimmune disorders as well as their supposed induction or triggering by SARS-CoV-2 vaccines. There is a growing need to assess the impact of the current pandemic particularly in patients with autoimmune bullous diseases requiring potent and long-term immunosuppressive treatments. This review provides the relevant state-of-the-art knowledge, including our own research, about immunobullous diseases in relation to COVID-19 and summarizes expert perspectives on their management throughout the pandemic.
Subject(s)
Autoimmune Diseases , COVID-19 , Pemphigoid, Bullous , Pemphigus , Humans , COVID-19 Vaccines , Pandemics , COVID-19/epidemiology , SARS-CoV-2 , Autoimmune Diseases/epidemiologyABSTRACT
Heat shock proteins (Hsps), including Hsp90 and Hsp70, are intra- and extracellular molecules implicated in cellular homeostasis and immune processes and are induced by cell stress such as inflammation and infection. Autoimmune bullous disorders (AIBDs) and COVID-19 represent potentially life-threatening inflammatory and infectious diseases, respectively. A significant portion of AIBDs remain refractory to currently available immunosuppressive therapies, which may represent a risk factor for COVID-19, and suffer from treatment side-effects. Despite advances in vaccination, there is still a need to develop new therapeutic approaches targeting SARS-CoV-2, especially considering vaccine hesitancy, logistical distribution challenges, and breakthrough infections. In this mini review, we briefly summarize the role of targeting Hsp90/70 as a promising double-edged sword in the therapy of AIBDs and COVID-19.
Subject(s)
Autoimmune Diseases , COVID-19 , Heat-Shock Proteins , Skin Diseases, Vesiculobullous , Humans , Autoimmune Diseases/drug therapy , Autoimmune Diseases/genetics , Autoimmune Diseases/immunology , COVID-19/genetics , COVID-19/immunology , Heat-Shock Proteins/genetics , Heat-Shock Proteins/immunology , HSP90 Heat-Shock Proteins/genetics , HSP90 Heat-Shock Proteins/immunology , SARS-CoV-2 , Skin Diseases, Vesiculobullous/drug therapy , Skin Diseases, Vesiculobullous/genetics , Skin Diseases, Vesiculobullous/immunology , HSP70 Heat-Shock Proteins/genetics , HSP70 Heat-Shock Proteins/immunology , COVID-19 Drug TreatmentABSTRACT
It is hypothesized that SARS-CoV-2 has the potential to elicit autoimmunity due to molecular mimicry between immunogenic proteins of the virus and human extracellular molecules. While in silico and in vitro evaluation of such immune cross-reactivity of human antibodies to SARS-CoV-2 proteins with several different tissue antigens has been described, there is limited information specifically pertaining to the immunological effects of COVID-19 and vaccines against SARS-CoV-2 on the development of autoimmune bullous diseases (AIBDs). Twelve seropositive post-COVID-19 individuals and 12 seropositive healthy volunteers who received two doses of the mRNA COVID-19 vaccine from Pfizer-BioNTech have been included in this case series investigation. Serum samples of these blood donors were tested for autoantibodies to the main immunobullous autoantigens, i.e., desmoglein 1, desmoglein 3, envoplakin, BP180, BP230, and type VII collagen. Our study revealed that none of the 24 anti-SARS-CoV-2 IgG-positive subjects had concomitant antibody reactivity with any of the tested autoantigens. These results argue against a relationship between SARS-CoV-2 infection/vaccines and AIBDs with respect to disease-triggering antibody cross-reactivity.
ABSTRACT
A link between Covid-19 and development of autoimmunity has been reported. A possible explanation could be molecular mimicry between SARS-CoV-2 and human proteins. Peptide sharing has been found between antigenic epitopes of this virus and heat shock proteins (Hsp) 60 and 90, both of which are associated with autoimmune diseases including those of the bullous type. In particular, there is evidence for the latter Hsp acting as a pathophysiological factor and treatment target in autoimmune blistering dermatoses. Considering multimodal anti-inflammatory mechanisms of action of anti-Hsp90 treatment and drug repositioning results, it may be hypothesized that Hsp90 inhibition could also be a treatment option for cytokine storm-mediated acute respiratory distress syndrome in Covid-19 patients. Hence, although Covid-19-induced autoimmune bullous diseases have not been described in the literature so far, the potential relationship between Covid-19, Hsp, and these autoimmune disorders deserves further attention with respect to both pathophysiology and treatment.