Vaccines, Genetics, and Autoimmune Diseases: A roundup of the research

Vaccines have been around in one form or another for about 200 years. They have saved millions of lives and prevented long-term suffering from diseases like tuberculosis and polio. While there is no denying that the human population as a whole benefit from vaccines, there are questions surrounding vaccinations and autoimmune diseases. On the one hand, certain vaccines may slightly increase the absolute risk of autoimmune diseases in susceptible individuals. The flip side is that some vaccines may protect against specific autoimmune diseases.

This is not a cut-and-dried topic, so stick with me through the ins and outs of the research. Note that no research yet shows an impact on autoimmune diseases from the brand new COVID-19 vaccine.

In this article, I’m just bringing together information from research studies — if you have medical questions, please consult your doctor.

Vaccines, Autoimmune Diseases, and Your Immune System

There are various types of vaccines, but the overarching goal is to cause an immune system response to a specific pathogen.  Vaccines prompt your body’s immune system to create a reaction – usually involving antibodies or a T-cell response against the virus or bacteria.

Most adverse events from vaccines are short-lived and transient, such as not feeling well the next day or having a sore spot where the shot was administered.[ref] But there are rare cases of more severe adverse reactions to vaccinations.[ref]

Autoimmune diseases and Infections:

Autoimmune diseases arise from the body mistaking a certain cell type for ‘foreign’ rather than ‘self’.

In general, autoimmune diseases are thought to be caused by a combination of genetic susceptibility, immune activation, hormones, and/or an environmental trigger.[ref] That ‘trigger’ can be an exposure to toxins, a trauma such as surgery, altered gut microbiome, pregnancy, or an infection by a virus or bacteria.

So how can a virus or bacterial pathogen cause an autoimmune reaction? Recent research shows that one way is through causing cell death. The immune system clears out the dead cells but the cells contain both the pathogen’s DNA and the host’s DNA. Therefore, this action triggers an immune response against both pathogen and host DNA.[ref]

Other research shows a pathogen could trigger an autoimmune disease due to molecular mimicry, which could happen if the pathogen antigen is similar to a host antigen.[ref]

Let me give you some examples of pathogens researchers associate with autoimmune diseases[ref]:

Autoimmune Disease Pathogen
Lupus Cytomegalovirus, Epstein-Barr Virus, T. gondii
Antiphospholipid syndrome Epstein-Barr Virus, C. tetani
Type 1 Diabetes Cytomegalovirus, Saccharomyces cerevisiae
Rheumatoid arthritis E. coliK. pneumoniae P. miriabilis, Epstein-Barr virus, endogenous retrovirus
Multiple sclerosis Epstein-Barr virus, Acinetobacter sp P. aeruginosa
Sjögren’s syndrome Coxsackie virus, Epstein-Barr virus

Keep in mind that the pathogen alone likely is not the single cause of the autoimmune disease. Instead, it is the pathogen along with genetic susceptibility, environmental factors, and possibly epigenetic changes.[ref]

Autoimmune diseases triggered by vaccinations:

Research now shows vaccinations may trigger some autoimmune diseases. Again – this is not a common event, and it is likely due to multiple factors including genetics, epigenetics, and environment.

In addition to the attenuated pathogen, vaccines also include adjuvants such as aluminum. These adjuvants are included to increase the immune response. Adjuvants can increase immune response by enhancing the injection site reaction, increasing the release of inflammatory cytokines, or translocating the antigens to the lymph nodes.[ref]

Example time: The 2009-2010 flu vaccine caused narcolepsy in genetically susceptible people.

While still a relatively uncommon occurrence, the H1N1 vaccine caused a 5 to 14-fold increase in the risk of narcolepsy in children and teens. Adults had a ~7-fold increase in risk.  In addition to the vaccine, all of the narcolepsy patients carried a specific genotype for HLA-DQB1*06:02.[ref][ref][ref]  Again, this was a rare convergence of genetic susceptibility, a specific vaccine, and likely unknown environmental factors. While rare (about 1 in 30,000 children), the fact that the flu vaccine was widely used caused many to end up with autoimmune-induced narcolepsy.[ref]

Other autoimmune diseases linked to vaccines include:

  • Macrophagic myofasciitis is an autoimmune reaction at the site of the injection that lasts for months to years. It is triggered by alum-containing vaccines in people with the HLA-DRB1*01 genotype.[ref]
  • In the 90s, it was determined that the relative risk of Guillain-Barre Syndrome increased by 4 to 8-fold following the flu vaccine (in comparison to people getting a tetanus shot). While the relative risk sounds scary, this was a rare side-effect of the vaccine when looking at the absolute risk.[ref] Guillain-Barre is an autoimmune condition that attacks the myelin sheath on peripheral nerves, eventually leading to whole-body paralysis.
  • Another study published in 2009 showed that Guillain-Barre Syndrome risk was increased when receiving either the flu vaccine or hepatitis B vaccine.[ref] Keep in mind that the flu vaccine changes yearly, so the data from the 90s and early 2000s may not be as relevant today.
  • One specific hepatitis B vaccine, Engerix B, was shown in a French study to increase the risk of CNS inflammatory demyelination (Multiple Sclerosis).[ref]
  • It has been known since the 1960s that the measles vaccine increases the risk of immune thrombocytopenia (an autoimmune condition causing decreased platelets). A 2008 study estimates that for every 40,000 children getting an MMR shot, the vaccine will cause 1 case of autoimmune thrombocytopenia.[ref]

While these examples are real and significant, vaccinations do not trigger autoimmune diseases for the vast majority of people. Many studies of specific vaccines show no link to an increased risk of autoimmune disease.[ref]

One research study on the increased risk of multiple sclerosis after vaccination concluded that “The short-term increase in risk suggests that vaccines may accelerate the transition from subclinical to overt autoimmunity in patients with existing disease.”[ref]  In other words, certain vaccines may just accelerate the autoimmune condition in people who are already partly there.

The good side of vaccines: killing cancer & preventing autoimmune diseases

Triggering an autoimmune reaction by a vaccine can be a good thing. One cell type the body needs to kill off is cancer cells. For the past four decades, researchers have known that the BCG vaccine (tuberculosis) causes the body to recognize and kill off bladder cancer cells.[ref][ref]

There are a number of different vaccines in trials now that specifically target different types of cancer. For example, the live attenuated measles vaccine may also help target glioblastoma cells. Additionally, a poliovirus vaccine is being revamped to target glioblastoma brain tumors.[ref][ref][ref]

Additionally, certain vaccines are linked with a lower risk of autoimmune diseases. Animal studies show that the BCG vaccine protects against type 1 diabetes in genetically susceptible animals. A clinical trial in Italy showed that the BCG vaccine decreased the risk of MS in people with early symptoms of the disease.[ref]

Research on vaccination safety in people with autoimmune diseases:

If you already have an autoimmune disease, you may be wondering if you are at risk for complications from a vaccine. This is something, of course, to talk with your doctor about for your individual circumstances.

You can also check out the CDC guidelines, which, for example, include people with autoimmune diseases who should not get the hepatitis B vaccine.[ref]

Research on specific autoimmune diseases and specific vaccines:

  • Trivalent influenza vaccine: A study of 24 patients with either lupus and/or rheumatoid arthritis showed no difference from a healthy control group.[ref]
  • Quadrivalent HPV vaccine: A study of 50 patients with lupus found no differences from healthy control in their reaction to the HPV vaccine.[ref]
  • Tetanus, hepatitis B, flu: A study of 643 MS patients found no increase in relapse due to vaccinations for tetanus, hep B, or the flu (1993-1997).[ref]
  • Live attenuated virus vaccines: Some government health agencies give a general recommendation against live attenuated virus vaccines for people with autoimmune diseases who are on immunosuppressant drugs.[ref]

 


Genetic variants, autoimmune diseases, and vaccines:

We are all individual and unique in our response to both pathogens and to vaccinations. This is due to genetic variations — and all together, it is an advantage to our population to have this variability.

Our body’s response to vaccination is largely genetic for some vaccines, such as measles, polio, and hepatitis B. Not everyone will mount a humoral response to a vaccine. Researchers estimate that 5-10% of vaccines do not produce a long-term antibody response.[ref]

To be honest, there isn’t a lot of research on genetic variants directly linking autoimmune diseases to vaccinations. The cynical outlook is that there isn’t any money in looking at the topic, but the more realistic view may be that vaccine-induced autoimmune diseases are uncommon and difficult to study.

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Aluminum adjuvants, HLA type, macrophagic myofasciitis:

Research does show that HLA-DRB1*01 significantly increases the risk of macrophagic myofasciitis, an autoimmune reaction against vaccines containing aluminum hydroxide as an adjuvant.[ref] As far as I can tell, this HLA type cannot be determined from 23andMe or AncestryDNA data.

HLA-DRB1*0401: serotype is linked to a much higher risk of RA and increased disease severity[ref]

Check your genetic data for rs660895 (tag for HLA-DRB1*0401) (23andMe v4; v5; AncestryDNA):

  • G/G: high risk of rheumatoid arthritis (~6-fold)[ref][ref] possibly increase risk of autoimmune/inflammatory syndrome induced by adjuvants (ASIA)[ref]
  • A/G: increased risk of RA, possibly increase risk of ASIA
  • A/A: typical risk

Members: Your genotype for rs660895 is .

Multiple Sclerosis and Pandemrix:

A possible link exists (reported in case studies) between HLA-DRB*15:01, the Pandemrix (flu) vaccine, and MS. Again, let me specify that this is a possible link in people who are already genetically susceptible to MS in response to a specific type of flu vaccine that was given a few years ago.

Check your genetic data for rs3135388 (23andMe v4, v5; AncestryDNA):

  • A/A: increased risk of MS[ref]
  • A/G: increased risk of MS
  • G/G: typical risk

Members: Your genotype for rs3135388 is .

Autoimmune risk factor variants that are also linked with response to vaccines:

The risk variant below are well studied and increase the risk for autoimmune diseases. They are also linked to alterations in vaccine response.

BUT… and this is important… there is no research specifically linking the variant to autoimmune disease caused by vaccination. Thus, this information is interesting but likely not clinically relevant.

IL2 gene: codes for interleukin-2, a cytokine important in the immune response

Check your genetic data for rs2069763 (23andMe v4, v5):

  • A/A: high antibody response to measles vaccination[ref] increased risk of autoimmune hepatitis[ref] increased risk of type 1 diabetes[ref]
  • A/C: increased risk of autoimmune hepatitis, type 1 diabetes.
  • C/C: typical

Members: Your genotype for rs2069763 is .

PTPN22 gene: codes for protein tyrosine phosphatase non-receptor type 22, which moderates signaling through T-cells (keeps them from being overactive).[ref][ref]

Check your genetic data for rs2476601(23andMe v4; AncestryDNA):

  • G/G: typical
  • A/G: increased risk of autoimmune diseases and endometriosis
  • A/A: increased risk of autoimmune diseases including: vitiligo[ref], Graves’ disease, type 1 diabetes[ref], Meniere’s disease[ref], juvenile arthritis[ref] psoriasis[ref] endometriosis[ref]; decreased T-cell response to trivalent influenza vaccine[ref]

Members: Your genotype for rs2476601 is .

IL-17F gene: codes for interleukin-17F, an inflammatory cytokine

Check your genetic data for rs763780 G7488A (23andMe V5 only)

  • T/T:  typical
  • C/T: increased risk of RA, autoimmune thyroid, increased risk of immune thrombocytopenia
  • C/C: increased risk of rheumatoid arthritis[ref][ref] increased risk of autoimmune thyroid disease[ref], increased risk of autoimmune thrombocytopenia[ref]

Members: Your genotype for rs763780 is .

 


Lifehacks:

While there are statistically significant increases in risk for certain autoimmune diseases associated with specific vaccines, the overall or absolute risk is still very low.

Talk with your doctor if you have questions about vaccinations, especially if you have an autoimmune disease. There are specific protocols and standards for vaccinations depending on the autoimmune disease and on certain immune system suppression medications.[ref]


Related Articles and Genes:

Lupus susceptibility and your genes
This article dives into the genetic variants that increase the susceptibility to lupus — and hopefully sheds some light on what is going on with your body’s immune system.

Chronic Inflammation & Autoimmune Risk – IL17
Inflammation can be blamed for everything from heart disease to mood disorders to obesity. Yet, how does this somewhat nebulous idea of too much inflammation tie into our genes?  It seems that some people have a more sensitive immune system and are more prone to inflammatory reactions.


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.