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====== Autoimmunity ======

Autoimmune inflammatory reactions encompass a group of immune responses where the body's immune system mistakenly targets its own tissues, resulting in inflammation and potential tissue damage. This phenomenon arises from a breakdown in the immune system's ability to differentiate between self and non-self antigens. The incidence in quite high cosidering recent studies.
[(General1>>
title: Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK
url: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00457-9/fulltext
)]
===== Causes =====

The underlying causes of autoimmune inflammatory reactions are complex. Genetic predispositions can make certain individuals more susceptible to autoimmune diseases. Additionally, environmental factors like infections, hormonal imbalances, and exposure to certain chemicals can trigger autoimmune responses. While autoimmune disorders have long been recognized, recent concerns have arisen regarding autoimmune reactions potentially linked to COVID-19 mRNA vaccines.
[(Vax1>>
title: New-onset autoimmune phenomena post-COVID-19 vaccination
url: https://onlinelibrary.wiley.com/doi/10.1111/imm.13443
)]
[(Vax2>>
title: COVID-19 Vaccination and the Rate of Immune and Autoimmune Adverse Events Following Immunization: Insights From a Narrative Literature Review
url: https://www.frontiersin.org/articles/10.3389/fimmu.2022.872683/full
)]
[(Vax3>>
title: Vaccinations and Autoimmune Diseases
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402446/
)]
[(Vax3bis>>
title: Autoimmune inflammatory reactions triggered by the COVID-19 genetic vaccines in terminally differentiated tissues
url: https://www.tandfonline.com/doi/full/10.1080/08916934.2023.2259123
)]
[(Vax4new>>
title: Covid-19: Regulators warn that rare Guillain-Barré cases may link to J&J and AstraZeneca vaccines
url: https://www.bmj.com/content/374/bmj.n1786/rr-0
)]
In general agents with immune-enhancing properties like infectious agents, silicone (breast implant), and aluminium salts (a common adjuvant), have been associated with immune-mediated diseases. Recently, conditions like siliconosis, Gulf War Syndrome, Macrophagic Myofasciitis Syndrome, and post-vaccination phenomena have been linked to prior exposure to these factors.
[(Other4>>
title: ASIA: Autoimmune/inflammatory syndrome induced by adjuvants
url: https://www.sciencedirect.com/science/article/abs/pii/S0896841110000788?via%3Dihub
)]
[(Other5>>
title: Acute polyarthritis after influenza A (H1N1) immunization
url: https://www.sciencedirect.com/science/article/abs/pii/S1297319X11000224?via%3Dihub
)]
[(Other6>>
title: Adjuvant Systems for vaccines: 13 years of post-licensure experience in diverse populations have progressed the way adjuvanted vaccine safety is investigated and understood
url: https://www.sciencedirect.com/science/article/pii/S0264410X19310199
)]
[(Other7>>
title: The value of Autoimmune Syndrome Induced by Adjuvant (ASIA) - Shedding light on orphan diseases in autoimmunity
url: https://www.sciencedirect.com/science/article/abs/pii/S1568997218300570
)]
In the case of HPV vaccine, several studies say that there is little correlation, 
[(HPV2>>
title: Human papillomavirus vaccination and risk of autoimmune diseases: A large cohort study of over 2million young girls in France 
url: https://pubmed.ncbi.nlm.nih.gov/28750853/
)]
but other studies demonstrate that there is relevant correlation, if data is analyzed properly and without bias. 
[(HPV5>>
title: The epidemiological profile of ASIA syndrome after HPV vaccination: an evaluation based on the Vaccine Adverse Event Reporting Systems
url: https://link.springer.com/article/10.1007/s12026-014-8567-3#Abs1
)]
[(HPV6>>
title: Letter to the editor – HPV vaccine and autoimmunity Incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease after quadrivalent human papillomavirus vaccination: a cohort study
url: https://pubmed.ncbi.nlm.nih.gov/27864851/
)]
A problem in several studies is that as control group are considered subjects that did take an other type of vaccine, instead of a real placebo. 
[(HPV1>>
title: HPV vaccine and autoimmune diseases: systematic review and meta-analysis of the literature
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196376/
)]
In several cases there was strong time correlation, so there are ongoing lawsuits.
[(HPV4>>
title: Gardasil Postural Orthostatic Tachycardia Syndrome (Pots) Lawsuits
url: https://justicecounts.com/dangerous-drug-lawsuits/gardasil-lawsuits/postural-orthostatic-tachycardia-syndrome-pots/
)]
[(HPV3>>
title: Postural tachycardia syndrome following human papillomavirus vaccination
url: https://onlinelibrary.wiley.com/doi/10.1111/ene.12272
)]





===== Mechanism =====

==== Loss of Immunological Tolerance ====

Autoimmune responses arise when the immune system falters in identifying self-antigens as benign. Normally, the body maintains a state of immunological tolerance, where the immune system refrains from reacting against its own cells and tissues. However, in autoimmune disorders, this balance is disrupted, leading to the generation of autoantibodies and the activation of autoreactive T-cells.

==== Inflammatory Response ====

Upon identifying self-antigens as foreign entities, the immune system initiates an inflammatory cascade. This entails the release of pro-inflammatory cytokines, chemokines, and the recruitment of immune cells to the affected tissues. The ensuing inflammation can result in tissue damage and impaired functionality.

==== Target Organs and Systems ====

Autoimmune disorders have the potential to affect a wide array of organs and systems within the body. Commonly impacted tissues encompass joints (as seen in rheumatoid arthritis), the central nervous system (as in multiple sclerosis), the skin (as in psoriasis), and the thyroid gland (as observed in Hashimoto's thyroiditis).

===== Common Autoimmune Inflammatory Conditions =====

==== Organ-specific diseases ====

Conditions where the immune system targets specific organs, potentially leading to organ dysfunction and related symptoms.

**Addison's Disease** is a rare condition where adrenal glands don't produce enough hormones, causing fatigue, weight loss, and low blood pressure.

**Coeliac Disease** is an immune reaction to gluten, damaging the small intestine lining and leading to digestive discomfort and malnutrition.

**Graves' Disease** is an autoimmune disorder causing an overactive thyroid gland, leading to symptoms like rapid heartbeat, weight loss, and anxiety.

**Hashimoto's Thyroiditis** is an autoimmune disorder where the immune system attacks the thyroid, causing an underactive thyroid gland and symptoms like fatigue and weight gain.

**Inflammatory Bowel Disease (IBD)** encompasses disorders like Crohn's disease and ulcerative colitis, characterized by prolonged inflammation of the digestive tract. Symptoms may encompass abdominal discomfort, irregular bowel movements, and unintended weight loss.

**Multiple Sclerosis** is a central nervous system condition that involves the immune system's attack on the protective myelin sheath encircling nerve fibers, resulting in compromised nerve function. This can lead to an array of neurological symptoms.

**Myasthenia Gravis** is a neuromuscular disorder causing muscle weakness and fatigue, often worsened with activity and improved with rest.

**Pernicious Anaemia** is a condition where the body can't absorb enough vitamin B12, leading to fatigue, weakness, and nerve problems.

**Primary Biliary Cholangitis** is a chronic liver disease where the bile ducts are damaged, potentially leading to liver scarring and related symptoms.

**Psoriasis** is a chronic skin condition characterized by patches of red, itchy, and scaly skin, often appearing on the elbows, knees, and scalp.

**Type 1 Diabetes** is a lifelong condition where the body doesn't produce insulin, necessitating regular insulin injections to regulate blood sugar.

**Uveitis** is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea.

**Vitiligo** is a skin condition causing loss of skin color in patches, often due to a lack of pigment-producing cells. It's not harmful but can be socially distressing.

===== Connective tissue diseases =====

**Ankylosing spondylitis** is a chronic inflammatory condition primarily affecting the spine, causing pain and stiffness.

**Polymyalgia rheumatica** is an inflammatory disorder characterized by muscle pain, stiffness, and discomfort, often in the shoulders and hips.

**Rheumatoid Arthritis** is a condition marked by persistent joint inflammation, resulting in discomfort, limited mobility, and joint deformities. It predominantly affects the hands, wrists, and feet.

**Sjögren's syndrome** is an autoimmune disorder causing dryness of the eyes and mouth, along with potential systemic complications.

**Systemic Lupus Erythematosus (SLE)** is a systemic autoimmune ailment with potential effects on various organs, including the skin, joints, kidneys, heart, and nervous system. It is distinguished by a broad spectrum of clinical presentations.

**Systemic Sclerosis** is a rare autoimmune disease causing thickening of skin and connective tissues, potentially affecting internal organs.

**Vasculitis** is a group of rare disorders characterized by inflammation of blood vessels, affecting arteries, veins, and capillaries. It stems from an overactive immune system mistakenly attacking the body's own vessels. Symptoms vary widely and may include fatigue, fever, joint pain, and organ-specific issues.

===== Risk factors =====

Genetics: Family history of autoimmune diseases is a significant risk factor.

Gender: Many autoimmune diseases, such as lupus and rheumatoid arthritis, are more common in females.
    
Hormonal Factors: Hormonal changes, particularly in women, can influence autoimmune disease development.

Infections: Certain infections may trigger autoimmune responses in susceptible individuals.    

Environmental Exposures: Exposure to certain chemicals, pollutants, or UV radiation may increase the risk of autoimmune diseases.

Smoking: Smoking is associated with an increased risk of various autoimmune diseases.

Chronic Stress: Prolonged or chronic stress may contribute to autoimmune disease development.

Diet and Gut Health: Poor diet and imbalanced gut microbiota may contribute to autoimmune diseases.

Medications and Exposures: Certain medications and occupational exposures may increase susceptibility to autoimmune diseases. For example mRNA vaccines also increase the risk of autoimmune diseases.


/*

        Study: "The genetics of complex autoimmune diseases: non-MHC susceptibility genes" by L. R. Brun et al.

        Study: "Gender and the prevalence of autoimmune diseases" by C. M. Fairweather and N. Petri.

        Study: "Hormones and autoimmune diseases: sex hormones and thyroiditis" by M. Zen and Y. G. Tomer.

        Study: "Infections as a risk factor for autoimmune diseases" by S. Saleh and N. H. Eid.

        Study: "Environmental exposures and autoimmune diseases: contribution of gut microbiome" by Y. Mu et al.

        Study: "Smoking and autoimmune rheumatic diseases" by E. Kallberg et al.

        Study: "Psychological stress and autoimmune diseases: a systematic review and meta-analysis" by K. Li et al.

        Study: "Gut microbiome and the risk factors in central nervous system autoimmunity" by R. W. M. Penders et al.
        Study: "Drug-induced autoimmunity: Mechanisms and trends in incidence" by R. W. Chalmers et al.
        
*/

===== Prevention =====

Preventing autoimmune diseases involves adopting a healthy lifestyle and avoiding known risk factors. While there's no guaranteed way to prevent these conditions, several practices may help reduce the risk:

**Maintaining a Balanced Diet** a diet rich in fruits, vegetables, whole grains, and lean proteins can support a healthy immune system. Some nutrients and vitamins can be helpful to mantain a normal functioning immune system, for example curcumin, vitamin B, vitamin C, vitamin D, vitamin E...
[(Diet1>>
title: Dietary factors in rheumatic autoimmune diseases: a recipe for therapy?
url: https://pubmed.ncbi.nlm.nih.gov/28405001/
)]
[(Diet2>>
title: Vitamin B Complex and Experimental Autoimmune Encephalomyelitis –Attenuation of the Clinical Signs and Gut Microbiota Dysbiosis
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955508/
)]
[(Diet3>>
title: Oral vitamins C and E as additional treatment in patients with acute anterior uveitis: a randomised double masked study in 145 patients
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1722862/
)]
[(Diet4>>
title: Vitamin D as a Nutri-Epigenetic Factor in Autoimmunity—A Review of Current Research and Reports on Vitamin D Deficiency in Autoimmune Diseases
url: https://www.mdpi.com/2072-6643/14/20/4286
)]

**Regular Exercise**: Regular physical activity supports overall health and may help regulate the immune system.
[(Exercise1>>
title: Physical activity and autoimmune diseases: Get moving and manage the disease
url: https://www.sciencedirect.com/science/article/abs/pii/S1568997217302835?via%3Dihub
)]

**Stress Management**: Chronic stress may contribute to autoimmune diseases. Practicing relaxation techniques like meditation or yoga can be beneficial.
[(Stress1>>
title: Association between stressful life events and autoimmune diseases: A systematic review and meta-analysis of retrospective case-control studies
url: https://www.sciencedirect.com/science/article/abs/pii/S1568997215002621?via%3Dihub     
)]
[(Stress2>>
title: Psychological Stress, Intestinal Barrier Dysfunctions, and Autoimmune Disorders: An Overview
url: https://www.frontiersin.org/articles/10.3389/fimmu.2020.01823/full    
)]
[(Stress3>>
title: Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1361287/
)]    

/*
    Adequate Sleep: Getting enough quality sleep is essential for a well-functioning immune system.
        Study: "Sleep and immune function" by L. R. Simpson et al.

    Avoiding Smoking and Excessive Alcohol Consumption: Both smoking and excessive alcohol consumption can negatively impact the immune system.
        Study: "Smoking and autoimmune rheumatic diseases" by E. Kallberg et al.

    Limiting Exposure to Environmental Toxins: Minimizing exposure to environmental pollutants and toxins may reduce the risk of autoimmune diseases.
        Study: "Environmental factors in autoimmune diseases" by M. J. Parks et al.

    Maintaining a Healthy Gut Microbiome: A balanced gut microbiome may help regulate the immune system and reduce the risk of autoimmune diseases.
        Study: "The gut microbiome and autoimmune diseases" by Y. Belkaid and T. Hand.

    Regular Health Check-ups: Early detection and management of underlying health conditions can help prevent the development of autoimmune diseases.
        Study: "Preventive health care in rheumatoid arthritis: focus on cardiovascular risk" by J. W. J. Bijlsma et al.

*/

Please note that while these practices are generally beneficial for health, there is no surefire way to completely prevent autoimmune diseases, as genetic and environmental factors also play a significant role in their development. Always consult with a healthcare professional for personalized advice and recommendations.


/*

===== Conclusions =====

Autoimmune inflammatory reactions represent a multifaceted group of disorders. Recent discussions have arisen regarding potential links with COVID-19 mRNA vaccines. Continuous research and thorough assessments of vaccine safety are crucial to address these concerns and guarantee the health and well-being of those receiving the vaccines. Precise studies on pharmacokinetics, pharmacodynamics, and genotoxicity play a pivotal role in making informed choices regarding vaccination strategies.

*/