Lupus

Lupus, officially known as Systemic Lupus Erythematosus (SLE), is an autoimmune disease affecting millions worldwide.² The term "autoimmune" refers to a condition in which the body's immune system, which normally protects against harmful pathogens, mistakenly attacks its own tissues. Like many autoimmune conditions, lupus is characterised by periods of remission (when symptoms are mild or absent) and flares (when symptoms worsen).²

While we don't fully understand what triggers these flares, a group called adenoviruses has caught researchers' attention.^1,3

What are adenoviruses?

Adenoviruses are common viruses that can infect people. They are known for causing a range of symptoms, from common colds to eye infections.¹ What makes adenoviruses interesting is their ability to interact with our immune system very complexly.^1,3 They can infect various cells and, therefore, cause a wide range of illnesses.

Adenoviruses are part of the Adenoviridae family. They are non-enveloped viruses, meaning they don't have an outer lipid (fat) membrane. Instead, they have a protein shell called a capsid that protects their genetic material, which consists of double-stranded DNA.¹ This structure allows them to survive in various environments and makes them resistant to many disinfectants. As a result, they can persist in the body for longer periods, which might suggest a potential link to chronic diseases.

Pathophysiology of Lupus 

In lupus, the immune system attacks the body's own tissues.² This leads to inflammation and damage in different parts of the body, such as the skin, joints, kidneys, and other organs.

In a healthy immune system, cells can distinguish between "self" (the body's own tissues) and "non-self" (foreign invaders). In lupus, this ability is compromised, a phenomenon known as loss of self-tolerance.² As a result of this loss of self-tolerance, the immune system produces autoantibodies.

These antibodies (proteins normally used to fight infections) target the body's own tissues, particularly components of the cell nucleus, like DNA and proteins.² These autoantibodies bind to self-antigens (parts of our own cells that the immune system mistakenly identifies as foreign). Once bound together, they can deposit in various tissues, causing inflammation and damage.²

These antibodies activate the complement system, a part of the immune system that enhances the ability of antibodies and immune cells to clear microbes and damaged cells. 

In lupus, overactivation of the complement system causes tissue damage.² Lupus is usually associated with an imbalance in cytokines, which are small proteins important in cell signalling. Of particular importance is the overproduction of type I interferons, a group of cytokines that play a crucial role in the immune response against viruses.⁸

T and B cells are white blood cells essential for immune function. In lupus, both types of cells do not function normally. B cells produce more autoantibodies, while T cells fail to regulate the immune response properly.² 

Additionally, there is often a problem with clearing away dead or dying cells. This can expose the immune system to more self-antigens, which can lead to an autoimmune response.²

How Might Adenoviruses Trigger Lupus Flares

Adenoviruses increase the production of type I interferons.^7,8 Lupus patients often already have high levels of these proteins (known as the "interferon signature"). 

What do interferons do, and what are they?

Interferons are a group of proteins that combat viruses by boosting immune defenses through cell signalling. Overproduction of these molecules can lead to an overreaction of the immune system.

Interferons help dendritic cells grow (important antigen-presenting cells) and enhance B cell differentiation and autoantibody production.^4,8

Some parts of the adenovirus look similar to our cells. This molecular similarity could confuse the immune system, causing it to attack both the virus and the body's own tissues, leading to¹¹ an autoimmune condition. This process, known as molecular mimicry, can trigger autoreactive T cells and create antibodies that mistakenly attack the body.^5,6 Inflammation from fighting the adenovirus can also activate immune cells that attack the body's own tissues, a process called bystander activation.¹⁰

Adenovirus infections can temporarily weaken the immune system, which normally keeps autoimmune responses in check, such as regulatory T cells (Tregs). Tregs prevent an overreaction of immune responses.¹² 

Adenovirus infection can trigger neutrophils to release NETs, web-like structures with antimicrobial proteins. In lupus, these NETs provide autoantigens and boost type I interferon production.¹³

Adenovirus infections in the digestive system could alter the balance of bacteria in the gut, a condition known as dysbiosis. Dysbiosis caused by viruses could lead to lupus flares.¹⁴

What is the evidence?

While these ideas are based on our understanding of how viruses and the immune system work together, we don't yet have strong evidence that adenoviruses actually trigger lupus flares. Some studies have found that lupus patients have more antibodies against adenoviruses than people without lupus, suggesting they might have been exposed to these viruses more often.¹⁵ There have also been a few reported cases of lupus flares following adenovirus infections.¹⁶ However, these findings don't prove that adenoviruses cause flares - they might just mean that lupus patients are more susceptible to infections.¹⁷

A deeper look and conclusion 

The relationship between adenovirus infections and lupus flares is likely complex, similar to what we have learned from the COVID-19 pandemic. As various factors influence COVID-19 outcomes, the same might be true for how multiple factors affect lupus patients.²²

Both viruses can trigger immune responses, potentially leading to lupus flares in susceptible individuals. The importance of diet, overall health, and environmental factors in COVID-19 severity suggests these elements also affect how lupus patients respond to viral infections. A healthy diet promotes a healthy gut and good metabolic health, which might help manage lupus and reduce the risk of flares triggered by infections.

The impact of infections on our bodies is linked to different factors, such as our daily diet, where we live, our lifestyle, and overall health.

During the COVID-19 pandemic, hand hygiene, social distancing, and quarantine were emphasised; however, less attention was given to factors affecting disease severity and death rates. Statistics showed that countries with high consumption of ultra-processed foods, poverty, and malnutrition had higher mortality rates, while those with healthier diets had lower death rates.19

Research suggests that diet may influence COVID-19 outcomes. Countries with high consumption of ultra-processed foods, common in Western diets, and those with diets high in refined carbs and sugars, tended to have higher death rates.²⁰

SARS-CoV-2, the virus that enters cells by attaching to the ACE2 receptor, which controls blood pressure and fluid balance, can have its effects influenced by high blood sugar levels. High blood sugar can alter these receptors and increase their expression, possibly making it easier for the virus to enter cells, though the details are still being studied.²¹ From this, it can be concluded that our daily diet can impact our immune defenses.

Ultra-processed and low-fibre foods can harm the gut microbiome, which helps control immune responses. The gut microbiome regulates cytokines, protein production and signalling molecules important for immune regulation. In severe COVID-19 cases, an overreaction called a "cytokine storm" can cause intense inflammation and organ damage.²² Additionally, sugar can destroy beneficial bacteria in the gut. People who consume more fibre and maintain a healthier gut also tend to have a better immune response.

Obesity and metabolic syndrome, often linked to poor diets, are risk factors for severe COVID-19. These conditions cause ongoing low-level inflammation, which may lead to a stronger inflammatory response during infection.²¹

What we eat impacts T cell function, which is vital for fighting infections like COVID-19. A lack of nutrients such as vitamin D, zinc, and selenium can weaken the immune system and may lead to worse COVID-19 outcomes.²²

FAQs

Is there any cure for lupus?

Unfortunately, there is no cure for lupus yet, but treatments can help manage the symptoms.

Can lupus go away on its own? 

Lupus doesn't go away, but symptoms can come and go, which is known as flares and remissions.

Is lupus contagious? 

No, lupus is not contagious. You can't catch it from or give it to someone else.

Summary

Lupus (SLE) is an autoimmune disease where the immune system attacks the body’s own tissues, leading to inflammation and organ damage. Adenoviruses, which usually cause common infections, may play a role in triggering lupus flares by increasing type I interferons, promoting autoantibody production, confusing the immune system through molecular mimicry, and disturbing gut health. Although some studies suggest a link, evidence remains limited, and other factors such as diet, lifestyle, and overall health likely influence how infections affect lupus patients.