The Role of Exposomes in the Pathophysiology of Autoimmunity

Presented at the 13th International Congress on Autoimmunity in Athens, Greece

Speaker: Aristo Vojdani

Publications:

Vojdani, A.; Vojdani, E. The Role of Exposomes in the Pathophysiology of Autoimmune Diseases I: Toxic Chemicals and Food. Pathophysiology 2021, 28, 513-543. https://doi.org/10.3390/pathophysiology28040034

Vojdani, A.; Vojdani, E.; Rosenberg, A.Z.; Shoenfeld, Y. The Role of Exposomes in the Pathophysiology of Autoimmune Diseases II: Pathogens. Pathophysiology2022, 29, 243-280. https://doi.org/10.3390/pathophysiology29020020

Key Takeaways:

• It is now known that genetics play a relatively small part in the pathophysiology of autoimmune disorders in general, and that environmental factors have a greater role.
• The role of the exposome, an individual’s lifetime exposure to external and internal factors, is a key component in the pathophysiology of autoimmune diseases.
• The most common environmental factors are toxic chemicals, food/diet, and pathogens/infections.
• The solution is to detect the trigger, remove it from the environment or diet, then repair the damage to the individual’s body and health.

Gene plus exposome factors that contribute to autoimmune diseases

The exposome is an individual’s lifetime exposure to a variety of external and internal factors

Environmental triggers of autoimmunity:

Toxic Chemicals

Mercury

• Exposure to mercury can occur through external pathways, such as environmental pollution, occupation, and the handling of items or products containing it; or through internal pathways, such as preservatives/adjuvants in drugs and vaccines, contaminated food, or dental amalgams.
• Even chronic low mercury exposure can trigger local and systemic inflammation in susceptible individuals, exacerbating the already ongoing autoimmune response in those suffering from autoimmunity.
• Exposure can cause dysregulation of autoimmune responses and aggravation of the immunotoxic effects associated with elevated titers of autoantibodies detected in serum

Occupational exposure to crystalline silica

• Has been linked to rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and antineutrophil cytoplasmic antibody (ANCA)-related diseases

Smoking

• Has been linked to RA, SLE, multiple sclerosis (MS), thyroid autoimmunity, and Crohn’s disease

Solvents or chemicals with similar structures

• Examples include vinyl chloride, perchloroethylene, trichloroethylene (TCE), or mixed solvents
• Has been linked to SSc and MS

Certain cosmetic chemicals

• Has been linked to RA, SLE, and primary biliary cholangitis (PBC)

Infections/Pathogens

Infectious agents can induce autoimmune disorders through the following mechanisms:

• Molecular mimicry
• Epitope spreading
• Viral persistence
• Bystander activation
• Polyclonal activation
• Autoinflammatory activation of innate immunity
• Dysregulation of immune homeostasis

The three best examples of autoimmune-inducing infectious agents are: oral pathogens, SARS-CoV-2, and the herpesvirus

• 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.
• SARS-CoV-2 has been called the autoimmune virus, and the following key points support this appellation:
  • Similarities in lymphocyte map or lymphocyte subpopulation patterns between COVID-19 and autoimmune diseases
  • Molecular mimicry between SARS-CoV-2 spike proteins, nucleoproteins and human autoantigens that contribute to autoimmune diseases
  • Reaction of both animal and human monoclonal antibodies made against SARS-CoV-2 spike proteins and nucleoproteins with human autoantigens
  • Reaction of antibodies made against human autoantigens with SARS-CoV-2 spike proteins and nucleoproteins
  • Detection of autoantibodies made against human autoantigens known to cross-react with SARS-CoV-2 in the sera of patients with COVID-19
• The human herpesvirus family includes human herpesvirus 1 (HSV-1 or HHV-1); herpes simplex virus type 2 (HSV-2 or HHV-2); the Varicella zostervirus (VZV or HHV-3); EBV or HHV-4; cytomegalovirus (CMV or HHV-5); human herpesvirus type 6 (HHV-6); and measles (rubeola)
  • EBV has been linked to Celiac Disease, Autoimmune Liver Disease, Inflammatory Bowel Disease, SLE. RA, Sjogren’s Syndrome, MS, Type 1 Diabetes, Polyneuropathy, and Thyroid Autoimmunity
  • HHV has been linked to MS, Guillain-Barre’ Syndrome, Thyroid Autoimmunity, Sjogren’s, SLE, Myalgic Encephalomyelitis (ME/CFS), Parkinson’s Disease, Alzheimer’s Disease, Epilepsy, Encephalitis, and Collagen Vascular Disease

Food/Diet

Aluminum ingestion and absorption from the GI tract

• May contribute to Crohn’s disease, celiac disease, and Alzheimer’s disease
• See: Vojdani A. Elevated IgG Antibody to Aluminum Bound to Human Serum Albumin in Patients with Crohn’s, Celiac and Alzheimer’s Disease. Toxics. 2021 Sep 4;9(9):212. doi: 10.3390/toxics9090212.

Industrial food additives

• Includes colorants, preservatives, emulsifiers, food glue, gluten, sugar, salt, gums, pesticides, and nanoparticles
• See: Lerner A, Matthias T. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmun Rev. 2015 Jun;14(6):479-89. doi: 10.1016/j.autrev.2015.01.009.

Plant aquaporins (in corn and soy especially)

• A subclass of patients with relapsing-remitting MS reacted to both plant and human AQP4 peptides. This immune reaction against different plant aquaporins may help in the development of dietary modifications for patients with MS and other neuroimmune disorders.
• See: Vojdani, Aristo & Mukherjee, Partha Sarathi & Berookhim, Joshua & Kharrazian, Datis. (2015). Detection of Antibodies against Human and Plant Aquaporins in Patients with Multiple Sclerosis. Autoimmune Diseases. 2015. doi: 10.1155/2015/905208.

Anti-lectin antibodies (in beans especially)

• The reaction of anti-lectin antibodies with human tissue components and their detection in RF-positive samples may describe mechanisms by which the production of antibodies against undigested lectins may contribute to the pathogenesis of some ADs.
• See: Vojdani A, Afar D, Vojdani E. Reaction of Lectin-Specific Antibody with Human Tissue: Possible Contributions to Autoimmunity. J Immunol Res. 2020 Feb 11;2020:1438957. doi: 10.1155/2020/1438957.

Wheat and milk are associated with a spectrum of autoimmune diseases

• A high percentage of MS patients harbored antibodies to bovine casein. The antibody cross-reactivity between cow’s milk and CNS antigens can also exacerbate demyelination.
• See: Chunder R, et al. Antibody cross-reactivity between casein and myelin-associated glycoprotein results in central nervous system demyelination. Proc Natl Acad Sci U S A. 2022 Mar 8;119(10):e2117034119. doi: 10.1073/pnas.2117034119.

Spectrum of autoimmune disorders associated with wheat proteomes

Spectrum of autoimmune disorders associated with milk proteomes