COVID-19, Autoimmunity and Vaccination Part 2

Posted on by Jesse Santiano, M.D.

This article can develop an autoimmune disease when antibodies originally directed against the SARS-CoV-2 virus attack human proteins.

This is concerning because anyone who got sick with COVID-19 or those who get vaccinated with the COVID-19 vaccine may have a theoretical possibility to develop autoimmune diseases.

Barebones Immune Response

The way we develop immunity towards germs like viruses, in this case, is for the body to recognize amino acid sequences or peptides in that particular invading virus.

The amino acid sequence may run in the hundreds, and in the case of the spike protein of the SARS-CoV-2, it is 1,273 amino acids. 

Amino acids are the building blocks of proteins. There are only 20 amino acids in all plants, and animals including viruses and bacteria.

It is not hard to imagine that with only 20 amino acids available, some amino acid sequences may be the same between species. An example will be some amino acids in the spike protein of the SARS-Cov-2 may be the same in some proteins present in the human body.

This is significant because an antibody generated by the immune response against a particular amino acid or peptide sequence of the SARS-CoV-2 may also react or attach to a human protein with the same amino acid sequence. This can lead to an immune response towards that protein and render it ineffective to do its function.

In the human body, anything with structure has proteins. Muscle, skin, nerves, blood vessels, and internal organs all have proteins. Proteins like enzymes, hormones, genes are important in the function and maintenance of the whole body. Even the smallest parts of the cells are made up of proteins.

During an infection like COVID-19, one may think that there is only one type of antibody produced against the SARS-CoV-2; however, that is not the case.

There are many different kinds of antibodies produced against the SARS-CoV-2. Remember the thousand-long amino acid sequence of the spike protein? Amino acid sequences as short as five are enough to generate an antibody response.

The World Health Organization in its webpage What we know about the
COVID-19 immune response said

• Antibodies develop against different proteins that are part of a virus.

 

The article, Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases, was originally published online in Clinical Immunology in May 2020.

In the experiment, mouse monoclonal antibodies against the SARS-CoV-2 were exposed to 50 different human tissue antigens. Antigens are substances that interact with antibodies. Antigens may be non-self or foreign as in viruses or “self,” which means part of the human body.

Mouse monoclonal antibodies were used to ensure that only antibodies that were tested to be against SARS-CoV-2 are present and there are no other antibodies.

Even though the antibodies were obtained from mice, their reaction with human antigens is a good approximation of how human antibodies to SARS-CoV-2 react to human antigens. That’s because they recognize the same amino acid sequences.

The experiment tested for the cross-reactivity between the central part of the virus called the nucleocapsid and the virus’s spikes.

For this article, I only included the antibodies’ reactions to the spike proteins of the SARS-CoV-2 since the present available COVID-19 vaccines are against the spike proteins only.

Human Antigens with the Greatest Reaction to SARS-CoV-2 Spike antibodies

Among the 50 human tissue antigens that they tested, the eleven had the greatest reaction.

  1. Transglutaminase 3, (tTG3)
  2. Transglutaminase 2 (tTG2)
  3. Extractable Nucleic Acid Antigen (ENA)
  4. Myelin Basic Protein
  5. Mitochondria
  6. Nuclear antigen (NA)
  7. α-myosin
  8. Thyroid Peroxidase (TPO)
  9. Collagen
  10. Claudin 5+6
  11. S100 B

The table below shows the intensity of the reaction between the antibodies to the SAR-SoV-2 antigen in red and the human antigens in blue.

From: Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases. Clin Immun Aug 2020

The significance of the results lies in the fact that these human antigens exist all over the body. That is why there is the potential that any immune response developed by the body against the SARS-CoV-2 may turn against the host and produce autoimmune disease.

The authors of the article mentioned their concern about this cross-reaction because the vaccine against COVID-19, which contains the messenger RNA of the SARS-CoV-2, can potentially cause autoimmune diseases to the recipients.

That’s because the spike protein mRNA in the vaccine will give the body instructions to make different kinds of antibodies against the SARS-CoV-2.

An autoimmune disease is when the body’s antibodies and the immune system attack the body’s antigens.  It can happen to any organ from head to toe and can be sudden or slow and long-lasting.

Proteins that Cross-React with SARS-CoV-2 antibodies and Autoimmune diseases

The following elaborates on the autoimmune diseases that can happen when the body develops an immune response against those proteins mentioned above.

Transglutaminase 3 (TG3)

Transglutaminase is important in creating protein polymers to create barriers and stable structures like the skin, the lining of the intestinal tract, and blood clots.

There are 9 transglutaminases in humans. Among them, transglutaminase 3 and 2 cross-reacts with SARS-CoV-2.

TG3 is high in dermatitis herpetiformis, the skin rash present in celiac disease.

Transglutaminase 2 (TG2)

The body gets injured by infection, environmental pollution, smoking, alcohol, and the likes, but it gets repaired with transglutaminase 2.

If TG2 is hampered, then excess scarring develops, and normal function suffers.

Diseases associated with disordered TG2

  • Progressive kidney disease
  • Pulmonary fibrosis
  • Systemic sclerosis affects the skin, blood vessels, muscles, heart, digestive system,
    lungs, and the kidneys
  • Liver cirrhosis
  • Celiac disease is a condition when the ingestion of gluten leads to intestinal damage.  Gluten is present in wheat, barley, and rice.
  • Cystic fibrosis affects the cells that produce mucus, sweat, and digestive juices. These secretions become thick, sticky, and hard to expel in cystic fibrosis.
  • Cardiovascular disease includes atherosclerosis, coronary heart disease, deep vein thrombosis, vascular calcification, cerebrovascular and peripheral arterial diseases, and rheumatic heart disease.
  • Neurological diseases like Alzheimer’s disease, Parkinson’s disease, supranuclear palsy, and Huntington’s disease

Disease with anti-Myelin Basic Protein

Myelin is the outer lining of nerves. Proper myelin structure is important for nerve function. Antibodies to myelin remove or demyelinate the outer cover making the nerve useless.

That is what happens in multiple sclerosis and peripheral neuropathy. Peripheral neuropathy presents as tingling, numbness of the hands and feet.

Disease with Antimitocondrial Antibody

The antimitochondrial antibodies are directed towards the liver cells, and they are detected in Primary Biliary Cholangitis. Formerly known as Primary Biliary Cirrhosis.

Diseases with Anti-Nuclear antigen (ANA)

ANAs have different subtypes. A subtype are extractable nuclear antigens.

Extractable Nucleic Acid Antigen (ENA)

ENAs are antigens from the nucleus of a cell. There are many kinds of antibodies to ENAs. A positive antibody to each ENA can confirm an autoimmune disease as shown in the following:

  1. anti-Sm for Systemic Lupus Erythematosus or SLE
  2. anti-RNP for Mixed Connective Tissue Disease 
  3. anti-La/anti-SS-B for Sjögren’s Syndrome
  4. anti-Ro/anti-SS-A for Sjögren’s Syndrome
  5. anti-Scl70 for Scleroderma, which affects the skin, connective tissue, and internal organs. The skin becomes tight, and scars develop in the internal organs.
  6. anti-Jo for Dermatomyositis, which presents as a skin rash and muscle weakness.

Other Anti-nucleic acid subtypes

  1. Anti-dsDNA are highly associated with Systemic Lupus Erythematosus.
  2. Anti-histone antibodies are found in Drug-induced lupus, SLE, scleroderma, rheumatoid arthritis, and undifferentiated connective tissue disease.
  3. Anti-glycoprotein 210 and anti-nucleoporin 62 or anti-p62 are present in approximately 25–30% of Primary Biliary Cirrhosis. 
  4. 2.5Anti-centromere antibodies  are associated with limited cutaneous systemic sclerosis, also known as CREST syndrome, primary biliary cirrhosis, and proximal scleroderma
  5. 2.6Anti-sp100 are found in 20–30% of primary biliary cirrhosis
  6. 2.7Anti-PM-Scl are found in up to 50% of polymyositis/systemic sclerosis (PM/SSc) overlap syndrome

α-myosin autoantibodies

α-myosin is present in the heart muscles. Antibodies to the α-myosin can induce myocarditis. Myocarditis is inflammation of the heart muscles. This can lead to heart failure and even death.

Thyroid Peroxidase (TPO) autoantibodies

Thyroid peroxidase is an enzyme normally found in the thyroid gland. The presence of antibodies to TPO suggests an autoimmune disorder to the thyroid like Grave’s disease or Hashimoto’s thyroiditis.

Anti-Collagen antibodies

Collagen is present all over the body. It is responsible for providing structure for the skin, joints, bones, blood vessels, and internal organs. Antibodies to collagen are found in several diseases like:

  1. Ankylosing spondylitis
  2. Emphysema
  3. Gout
  4. Juvenile chronic arthritis
  5. Lepromatous leprosy
  6. Osteoarthritis
  7. Osteoporosis
  8. Paget’s disease
  9. Psoriatic arthritis
  10. Relapsing polychondritis
  11. Rheumatoid arthritis (RA)
  12. Scleroderma
  13. Systemic lupus erythematosus
  14. Traumatic synovitis

Diseases associated with Claudin 5 Dysfunction

Claudin 5 is an important part of the tight junction proteins that provide a protective barrier preventing unwanted and potentially damaging material to the brain from the blood vessels.

From the article, Claudin-5: the gatekeeper of neurological function.

Claudin 5 is the most enriched tight junction protein and its dysfunction has been implicated in neurodegenerative disorders such as Alzheimer’s disease, neuroinflammatory disorders such as multiple sclerosis as well as psychiatric disorders including depression and schizophrenia.

Claudin 6

Claudin 6 is a relatively new protein discovery, and autoimmune diseases related to it are not yet reported.

Diseases associated with S100 B abnormality

S100B is a protein that is essential for proper brain function and maintenance. Antibodies to S100 B have been seen to be elevated in depressive disorder, epilepsy, multiple sclerosis, and Parkinson’s disease.

Take-Away Message

There exist a potential for the COVID-19 spike protein vaccine to create autoimmune diseases. This article is not an anti-vaccine article but hopes to provide caution among those thinking of getting vaccinated.

Vaccines have helped humanity, but more care should be observed in vaccine development so that the protein sequences will not mimic the human proteins.

Knowledge about Covid-19 is rapidly evolving. Information may update as new researches are done. Stay current by subscribing. Feel free to share.

Don’t Get Sick!

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  4. COVID-19, Autoimmunity, and Vaccination
  5. AeroNabs are Nanobodies against COVID-19
  6. Vitamin B1 or Thiamine in Infections
  7. The MATH+ Protocol Results in Greater Survival in Hospitalized COVID-19 Patients
  8. Antibodies to COVID-19 can Exist in the Uninfected
  9. Zinc Deficiency Impairs the Immune System
  10. Vitamin C and COVID-19
  11. Any Science behind Elderberry for Influenza and Covid-19?

Featured articles:

Vojdani A, Kharrazian D. Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue can be linked to an increase in autoimmune diseases. Clin Immunol. 2020;217:108480. doi:10.1016/j.clim.2020.108480

Szondy Z, Korponay-Szabó I, Király R, Sarang Z, Tsay GJ. Transglutaminase 2 in human diseases. Biomedicine (Taipei). 2017;7(3):15. doi:10.1051/bmdcn/2017070315

Image Credit:

Structure of a SARS-CoV virion By SPQR10 – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=88349537

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