Post-vaccination autoimmunity: causes, signs, and risk groups

Vaccination and autoimmunity: a complex balance

Vaccination is one of the most effective public health tools, preventing millions of cases of infectious diseases and saving lives worldwide [2, 6]. However, like any medical intervention, vaccines can cause side effects. Among these, special attention is paid to the potential link between vaccination and the development of autoimmune diseases (ADs) [1, 2, 4].

Autoimmune diseases occur when the body's immune system mistakenly attacks its own healthy tissues. They develop in genetically predisposed individuals but require an external trigger, which is often an infection [4]. Discussions about whether vaccines, which mimic infections, can also act as such triggers have been ongoing for a long time [4]. It is important to note that, with the exception of some specific cases, a causal link between vaccination and most ADs has not yet been definitively established [1, 6]. Post-vaccination autoimmune phenomena are extremely rare but can be serious [1, 6].

How can vaccines affect the immune system?

The mechanisms by which vaccines could theoretically contribute to the development of autoimmune reactions include:

• Molecular mimicry: Antigens of microorganisms contained in vaccines may have structural similarities to the body's own antigens. This can lead to the immune system, trained to respond to the vaccine antigen, attacking similar self-molecules [4, 5].
• Bystander activation: An immune response to vaccine components or adjuvants can cause non-specific inflammation and tissue damage. This, in turn, can lead to the release of self-antigens and their presentation to the immune system, triggering an autoimmune reaction [4, 5].
• Adjuvants: Many vaccines contain adjuvants – substances that enhance the immune response to a vaccine antigen [2]. It has been described that adjuvants may be associated with the development of the so-called ASIA syndrome (Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants) [1, 2]. This syndrome encompasses a range of autoimmune and autoinflammatory conditions arising after exposure to adjuvants, including those contained in vaccines [2].

Which autoimmune reactions are linked to vaccination?

Despite their overall rarity, some autoimmune conditions have been linked to vaccination, although many of them require additional epidemiological studies to confirm the association [5]. The most well-known examples include:

• Guillain-Barré syndrome (GBS): A rare neurological disorder associated with the 1976 swine flu vaccine [1, 5].
• Immune thrombocytopenic purpura (ITP): Cases have been noted after vaccination against measles, mumps, and rubella (MMR) [1, 5].
• Transverse myelitis: A rare clinical syndrome in which an immune-mediated process causes damage to the spinal cord. A systematic review identified 37 reported cases of transverse myelitis associated with various vaccines (including hepatitis B, MMR, and diphtheria-tetanus-pertussis vaccines) in children and adults. In most cases, the temporal association ranged from a few days to 3 months, although sometimes longer [3].
• Myopericarditis: Reported after smallpox vaccination [5].
• Thrombotic events after COVID-19 vaccination: Following the use of adenovirus vector vaccines against SARS-CoV-2, rare cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) were reported, and after mRNA vaccines, rare cases of deep vein thrombosis. These conditions may, at least in part, be related to an autoimmune reaction triggered by the vaccine [7].
• Other conditions: There are isolated reports of cases of arthritis, vasculitis, and symptoms involving the central or peripheral nervous system after vaccination, but these are extremely rare, and usually only short-term outcomes are described [1].

It is important to note that some suspected links, such as between the hepatitis B vaccine and multiple sclerosis, have not been confirmed in large studies, although they have been re-examined recently, and the link between childhood immunization and type 1 diabetes appears to have been definitively refuted [5].

Who is in the risk group?

Defining risk groups for the development of post-vaccination autoimmunity, especially ASIA syndrome, can help further limit the number of such cases. Potentially susceptible groups include [2]:

• Individuals with prior post-vaccination autoimmune phenomena: Those who have already experienced autoimmune reactions after previous vaccinations.
• Patients with a medical history of autoimmune diseases: Individuals already diagnosed with any autoimmune disease.
• Patients with a history of allergic reactions: Although this is not directly autoimmunity, a tendency toward strong immune reactions may be a factor.
• Individuals predisposed to the development of autoimmunity: This includes people with a family history of autoimmune diseases or with certain genetic markers (e.g., specific HLA types) that increase the risk of ADs [2, 4].

Understanding these risk factors allows physicians to take a more individualized approach to vaccination, especially in cases where potential risks may outweigh the benefits for a specific patient, although such situations are extremely rare.

Diagnosis and perspectives

Establishing a causal link between vaccination and the development of an autoimmune disease is a complex task. This is due to the rarity of such events, their acute or delayed manifestation, and the long latent period, which can vary from a few days to several years [6]. Furthermore, autoimmune diseases are widespread in the population (up to 1 in 20 people in Europe and North America have some form of AD), and their development is often linked to a multitude of environmental factors [4].

Despite these complexities, it is important to continue research to better understand the mechanisms, identify risk groups, and develop safer vaccines. The goal is not to abandon vaccination, but to minimize rare side effects through a personalized approach and careful monitoring. Patients experiencing unusual or persistent symptoms after vaccination should immediately consult a physician to evaluate their condition and rule out possible complications.

Sources

1. Vaccination and Induction of Autoimmune Diseases.
2. Predicting post-vaccination autoimmunity: who might be at risk?
3. Transverse myelitis and vaccines: a multi-analysis.
4. Vaccination and autoimmune disease: what is the evidence?
5. Could autoimmunity be induced by vaccination?
6. Vaccines and autoimmunity.
7. Autoimmunity roots of the thrombotic events after COVID-19 vaccination.
8. Influenza and autoimmunity.

The information provided in this article is for reference purposes only and does not replace professional medical advice. All decisions regarding vaccination and the treatment of autoimmune diseases should be made on an individual basis after consultation with a qualified physician.