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What is The Cause of Lupus Disease? 

 April 9, 2024

By  Linda Rook

Introduction.

Lupus is a chronic autoimmune disease, that need more research, due to its complex causes. This blog will explain the analysis, by delving into the complex causes of lupus. The surrounding factors of genetic, and environment, hormonal influences, and other factors.

Lupus, formally known as systemic lupus erythematosus (SLE), stands as a typical example of the unknown nature of the autoimmune diseases. Considered by many clinical symptoms such as skin rashes and joint pain, to severe organ connection.

If you develop lupus, it can be very challenging to you and your healthcare team.

Genetic: 

Genetics plays a significant role in the development of lupus, serving as a starting point in the complex interaction of factors that contribute to the disease. Understanding the genetic landscape of lupus has been the main point of research, shedding light on the specific genes and pathways concerned with disease vulnerability.

Certain genes such as human leukocyte antigen or HLA, which is located in chromosome 6, are the major players in lupus. Also, various other genes such as HLA class II genes, these genes have cell surfaces of proteins that are involved in antigen presentation in T-cells. Therefore, playing a major part in the immune system.

In addition to HLA genes, there are many non-HLA genetic alternatives, that have been implicated in lupus susceptibility through studies called genome-wide association studies or (GWAS). These alternative genetics span a wide range of genes involved in your immune function.

Furthermore, studies of family combinations and twin studies have shown evidence that hereditary is a significantly higher risk of developing the disease compared to the general population. However, the inheritance pattern of lupus is complex and involves multiple genetic factors interacting with the environmental triggers and modifications of DNA that regulate whether the genes are turned on or off.

Despite significant advancements in understanding the genetic basis of lupus, much remains to be clarified regarding the precise genetic variants contributing to disease pathogenesis.

Blood test for DNA.

Environmental Triggers. 

Environmental triggers are outside factors that can speed up the development of lupus or worsen flare-ups in susceptible individuals. These triggers can include various things like ultraviolet (UV) radiation, infections, hormonal changes, medications, and toxins.

Understanding the role of these triggers in lupus is crucial for unravelling how genetics and the environment interact to cause the disease.

UV radiation, especially from sunlight, is a major trigger for lupus, particularly causing skin rashes and lesions. It damages DNA, triggers cell death, and boosts the production of inflammatory substances, worsening lupus symptoms. UV radiation can also worsen systemic lupus erythematosus (SLE) by increasing the production of harmful antibodies and promoting inflammation that damages tissues and organs.

Sun glasses, UV glaze.

Infections, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human parvovirus B19, are linked to increased lupus risk. They can disrupt immune tolerance and lead to the production of autoantibodies typical of lupus. Bacterial and fungal infections can also trigger lupus flares in similar ways, showing the role of infectious agents in autoimmune responses.

Hormonal changes, particularly fluctuations in estrogen levels, can trigger lupus flares by affecting immune responses. Estrogen activates B cells, exposes T cells, and changes cytokine production, worsening autoimmune reactions in lupus. Hormonal shifts during puberty, pregnancy, and menopause can coincide with increased lupus activity in vulnerable individuals.

Medications and chemical toxins are additional triggers for lupus. Some medications can induce autoantibody production, disrupt immune tolerance, and promote inflammation, mimicking lupus symptoms. Exposure to toxins like silica, solvents, and pesticides is linked to increased lupus risk and severity, suggesting environmental pollutants play a role in autoimmune responses.

Chemical toxin bottles

Immune system not working.

When your body loses control of its immune response, it can either fail to fight off foreign invaders effectively, leading to the rapid spread of infections, or mistakenly attack its own healthy cells because it can't tell the difference between antigens and foreign pathogens.

In lupus, B cells are crucial as they produce autoantibodies targeting specific antigens like double-stranded DNA (dsDNA) and ribonucleoproteins. Problems with B cell activation, survival, and diversity, combined with faults in tolerance mechanisms, lead to immune tolerance breakdown and the emergence of B cells that attack healthy cells.

regularity T cell blood test

In lupus, CD4+ T cells have two main functions: they assist autoreactive B cells and contribute to inflammation by releasing cytokines. Cells like Th1 and Th17 also release pro-inflammatory cytokines like interferon-gamma (IFN-γ) and interleukin-17 (IL-17). Tregs, which normally keep the immune system balanced and prevent autoimmune responses, don't work properly in lupus patients. This worsens immune problems and makes the disease progress further.

Understanding how the immune system works are crucial in lupus, as it involves problems with immune tolerance, abnormal activation of certain immune pathways, and issues with regulatory functions. Figuring out the detailed biological processes behind these immune system problems is vital for finding new treatments and strategies to restore balance in the immune system and slow down the progression of the disease.

Research focused on unravelling these complexities will help us better understand how lupus develops and ultimately improve outcomes for patients.

Hormonal Influences.

Hormonal factors play a big role in lupus, leading to differences in how the disease affects men and women. Estrogen, progesterone, and androgens, like testosterone, influence the immune system, affecting the risk, severity, and flares of lupus.

Estrogen, in particular, is closely linked to lupus. It activates B cells, encouraging them to produce more antibodies, a key feature of lupus. It also affects T cells, promoting inflammation, and interferes with regulatory T cell function, creating an environment that favours lupus flares. Hormonal changes during puberty, menstruation, pregnancy, and menopause coincide with changes in lupus symptoms. For example, pregnancy can worsen the condition for about half of women with lupus, while menopause, with its lower estrogen levels, might reduce symptoms for some.

While estrogen is often the focus, androgens like testosterone also influence lupus. They have a calming effect on the immune system, inhibiting B cell activity, encouraging the expansion of regulatory T cells, and reducing inflammation. Men with lupus, who generally have higher androgen levels, often have milder symptoms, suggesting a protective effect.

Understanding how hormones interact with the immune system in lupus is crucial for developing personalized treatments. Further research into these mechanisms will help improve outcomes for lupus patients.

Epigenetic mechanisms.

Epigenetic mechanisms are crucial for controlling gene expression and cellular function in lupus, affecting disease susceptibility, progression, and variety. These mechanisms involve changes like DNA methylation, histone modifications, chromatin remodelling, and regulation by non-coding RNA. When these mechanisms go awry in lupus, they lead to abnormal gene expression patterns, immune problems, and inflammation, contributing to the disease.

In lupus, DNA methylation is extensively studied. It involves adding methyl groups to certain parts of DNA without changing the DNA sequence. In lupus, DNA often becomes under-methylated, especially in regions that control gene activity, which leads to increased expression of genes involved in inflammation and autoimmunity. Genes responsible for producing type I interferon (IFN), crucial in lupus, also become overactive due to under-methylation. Additionally, the under-methylation of genes involved in immune regulation worsens autoimmune problems in lupus.

Conclusion.

In summary, lupus is a complex autoimmune disease involving disrupted immune responses, ongoing inflammation, and tissue damage. Its development is influenced by various factors such as genetics, environment, immune system dysfunctions, hormones, and epigenetics. Understanding how these factors interact is crucial for understanding lupus and developing effective strategies for diagnosis, treatment, and prevention.

Genetic factors, including variations in genes related to immune function, contribute to a person's susceptibility to lupus. Environmental triggers like UV radiation, infections, and hormonal changes can worsen lupus symptoms, especially in those genetically prone to the disease. Immune system dysregulation, involving problems with immune tolerance and overactivation of immune pathways, drives inflammation and autoantibody production in lupus.

Hormonal influences, particularly estrogen, progesterone, and androgens, affect immune responses and disease activity in lupus patients. Changes in hormone levels during puberty, menstruation, pregnancy, and menopause coincide with fluctuations in lupus symptoms, showing the intricate relationship between hormones and immune function in lupus. Additionally, epigenetic mechanisms, which control gene expression, also contribute to immune dysfunction in lupus.

Advancing our understanding of lupus requires considering all these factors together. Developing treatments that target immune balance, reduce inflammation, and address hormonal imbalances could improve outcomes for lupus patients. Personalized treatment approaches, based on individual genetic and hormonal profiles, may also enhance treatment effectiveness while minimizing side effects.

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I am not a medical professional, and this blog is for information only. If you have any worries, you should consult your doctor.

I hope this blog has helped.

More Information.

https://www.mayoclinic.org/diseases-conditions/lupus/symptoms-causes/syc-20365789

https://versusarthritis.org/about-arthritis/conditions/lupus-sle/

https://www.cdc.gov/lupus/facts/detailed.html

Linda Rook

Linda is now retired and has suffered from Osteoarthritis for about 40+ years.  She struggled with her weight until she found the correct one that also helped with her arthritic pain.  Linda was in terrible pain until the physician thought her right hip needed replacement. 


Now Linda has an artificial right hip, which has left her with the left leg shorter than the right.  Therefore, her spine is now wonky, and has arthritis of the lower back, also it seems to be going all over the body, her pain is now in the knees, elbow, wrist, fingers and both hips.


Linda now spends her days writing information to help others with the same conditions, so they do not suffer like Linda.


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