The Role of Exposomes in the Pathophysiology of Autoimmune Diseases II: Pathogens

Abstract

In our continuing examination of the role of exposomes in autoimmune disease, we use this review to focus on pathogens. Infections are major contributors to the pathophysiology of autoimmune diseases through various mechanisms, foremost being molecular mimicry, when the structural similarity between the pathogen and a human tissue antigen leads to autoimmune reactivity and even autoimmune disease. The three best examples of this are oral pathogens, SARS-CoV-2, and the herpesviruses. Oral pathogens reach the gut, disturb the microbiota, increase gut permeability, cause local inflammation, and generate autoantigens, leading to systemic inflammation, multiple autoimmune reactivities, and systemic autoimmunity. The COVID-19 pandemic put the spotlight on SARS-CoV-2, which has been called “the autoimmune virus.” We explore in detail the evidence supporting this. We also describe how viruses, in particular herpesviruses, have a role in the induction of many different autoimmune diseases, detailing the various mechanisms involved. Lastly, we discuss the microbiome and the beneficial microbiota that populate it. We look at the role of the gut microbiome in autoimmune disorders, because of its role in regulating the immune system. Dysbiosis of the microbiota in the gut microbiome can lead to multiple autoimmune disorders. We conclude that understanding the precise roles and relationships shared by all these factors that comprise the exposome and identifying early events and root causes of these disorders can help us to develop more targeted therapeutic protocols for the management of this worldwide epidemic of autoimmunity.

Persistent SARS-CoV-2 Infection, EBV, HHV-6 and Other Factors May Contribute to Inflammation and Autoimmunity in Long COVID

“…Many pathogens, including viruses and bacteria, contain superantigens that are capable of activating T and B cells in a non-specific manner, producing a variety of autoantibodies in patients with multisystem inflammatory syndrome and patients with acute COVID-19 [ 107 , 108 ]. Finally, the reactivation of herpesviruses, particularly EBV and HHV-6 [ 29 , 30 ] that not only share a significant homology with SARS-CoV-2 spike protein [ 4 , 103 ] but co-infection with these viruses may change the structure of the ACE2 receptor on the epithelial cell in such a way that SARS-CoV-2 will complete its infective cycle much more efficiently (see Figure 4 ). In fact, in a subgroup of patients with long COVID, very high levels of antibodies against EBV and HHV-6 were reported [ 44 ].…”

“…The severity and recovery time for each case varies depending on each patient’s previous health history [ 1 , 2 ]. This inter-individual difference in combatting the virus is dependent on the gene as well as the exposome [ 3 , 4 ]. The exposome is an individual’s lifetime exposure to a variety of external and internal factors [ 5 , 6 ].…”

The Influence of SARS-CoV-2 Pandemic on the Diagnosis of Celiac Disease and Clinical Practice in Pediatric Gastroenterology

“…On the other hand, an absolute reduction in the number of newly diagnosed patients may have also been related to new factors that are currently unknown. Growing evidence supports the role of individual and environmental exposome in the incidence of autoimmune diseases [ 33 , 34 ]. Several birth cohort studies have reported the association of gastrointestinal infections with transglutaminase antibody seroconversion and an increased risk of CD later in life [ 35 , 36 ].…”

Cross-reactivity and sequence similarity between microbial transglutaminase and human tissue antigens

“…Genetic predisposition is pivotal for autoimmune diseases (ADs) development, but environmental factors are necessary for their clinical evolvement 1 – 4 . Pending on their association with various ADs, they include: hygiene and diet 5 , food processed additives 6 – 9 , trace elements 10 , enteric microbial peptides 11 , multiple infectious agents 3 , 12 – 15 , various vaccines 16 , 17 , toxic agents or food products 4 and recently the checkpoint inhibitors 18 , 19 . In fact, many of those environmental factors were cited as part of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 1 , 20 , 21 .…”

“…In fact, many of those environmental factors were cited as part of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 1 , 20 , 21 . Zooming into the gastrointestinal tract (GIT), many of the above-mentioned environmental factors inhabit the enteric lumen and are associated with local or peripheral ADs 3 – 13 , 22 .…”