How does Autoimmune Disease occur, and there is anything that can be done to help deal with it? The immune response in autoimmune disease acts exactly as it would against infection, with the big exception being that the target is the body's own (self) antigens. These become the target of the adaptive immune response. This drives a chronic inflammatory process that disrupts the normal function of the tissue.
The clinical progress of autoimmunity is often marked by a relapsing and remitting course. This occurs because there is both a continuing pro-inflammatory, disease-causing drive (in the form of a persistent antigen), and an opposing anti-inflammatory regulatory aspect.
Symptoms of Autoimmune Diseases
Different autoimmune diseases may have similar early symptoms, and also be seen in non-autoimmune conditions. These can include:
skin rashes
fatigue
dizziness
low grade fever
muscle aches
swelling
trouble concentrating
numbness and tingling in your hands and feet
hair loss
It's important to be tested, but not panic if you have the above symptoms as they can be come from many sources, and not always autoimmune issues.
Types of Autoimmune Diseases
Autoimmune responses can be localised to specific organs, or widespread and systemic.
Connective Tissue Disease
Connective tissue diseases are rheumatic diseases and include Systemic lupus erythematosus, systemic sclerosis, Sjogren’s syndrome and myositis.
The autoantibodies are directed against target antigens located in the nucleus (anti-nuclear antibodies) and include nucleic acids, cell nuclear proteins and ribonuclear proteins.
The gold standard pathology test is to screen for this with an ANA test (anti-nuclear antibody test). This is initially preformed by an immunofluorescence (IIF) test against human epithelial cells (HEp-2) which is known for its high sensitivity and specificity. Hence you may see a pathology result that reads as the screening pattern and the screening dilution that it stops fluorescing.
Vasculitis
Vasculitis is a general term that refers to inflammation of the blood vessels. It is used to describe a family of rare diseases, characterised by narrowing, weakening or scarring of the blood vessels, which can restrict blood flow and damage vital organs and tissues. Hence the condition is serious.
In Vasculitis, autoantibodies are directed against antigens found in the cytoplasm of neutrophils (and monocytes), specifically the cytoplasmic granules. These are known as anti-neutrophil cytoplasmic antibodies (ANCA). You may see a pathology result with the type of pattern seen (p-ANCA, c-ANCA) and the screening dilution it stopped fluorescing at.
Coeliac Disease
Coeliac Disease causes severe inflammation and damage to the mucosa of the small intestine via an autoimmune process. This results in nutrient absorption issues and potentially malnourishment, and is often a typical test screened for when you are iron deficient for example.
Gliadin (a protein that makes up the majority of gluten in bread), can only be partially digested in the small intestine. Should there be intestinal epithelial gaps (leaky gut or intestinal permeability); which is common from eating gluten; then the partially digested gliadin makes its way through to the underlying connective tissue. Here, the enzyme known as tissue transglutaminase (tTG) deamidates the amino acids in the gluten to deamidated gliadin peptides (DGP), allowing the body reason to mount an immune response. This is the reason you will see pathology results for tTG IgA and DGP IgG if you are screened for Coeliac Disease.
In individuals with the presence of human leucocyte antigens (HLA) DQ2 and DQ8, their B lymphocyte cells form antibodies against DGP (IgG) and their body’s tTG (IgA auto-antibodies). In addition, T cells secrete proinflammatory cytokines, causing inflammation.
As tTG IgA antibodies are tested for, you must also be evaluated for IgA deficiency which is quite common. If you are IgA deficient, this will alert the practitioner to any negative result with clinical suspicion. Genetic screening for HLA-DQ2/ DQ8 rules out the possibility of Coeliac Disease should you be negative for those HLA types. It is the best method of evaluating Coeliac Disease.
Gastrointestinal Disease
Inflammatory Bowel Disease (IBD) includes Ulcerative Colitis (UC) and Crohn’s Disease (CD).
Ulcerative colitis shows an immune reaction against the colon and rectum which can spread continuously from the anal region upwards.
Crohn’s disease shows an immune reaction against the small and large intestine but can be found in the oral cavity to the anus. It appears as non-continuous attacks.
Differentiation between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) is done by testing for Faecal Calprotectin and will be positive in IBD but negative in IBS.
Autoimmune gastritis is a chronic inflammation of the stomach hindering Vitamin B12 uptake. Pernicious anaemia (B12 deficiency) develops over time. Autoantibodies against gastric parietal cells of stomach (GPCA) and Intrinsic Factor (IF) deficiency that are needed to bind Vitamin B12, are tested when Pernicious Anaemia is suspected.Â
Autoimmune Liver Disease
Autoimmune Hepatitis (AIH) needs to be ruled out from hepatitis viruses. If untreated it will lead to cirrhosis of the liver. It can include Autoimmune Hepatitis, Primary Biliary Cholangitis, or Primary Sclerosing Cholangitis.
Anti-phospholipid Syndrome (APS)
If you have anti-phospholipid syndrome (APS), you may clinically present with:
vascular thrombosis
premature births
miscarriages
eclampsia
Your pathology results may show antibodies against:
Cardiolipin (ACA)
B2 glycoprotein (anti-B2GP1)
Positive lupus anticoagulant (LA)
To be classified as having APS you just have both a clinical and pathology confirmation.
Rheumatoid Arthritis
Rheumatoid arthritis is characterised by painful, swollen joints, movement restriction and progressive joint destruction from the formation of immune complexes. Approximately 70% of patients develop earlier autoantibodies against cyclic citrullinated peptides (CCP).
Autoimmune Skin Diseases
Pemphigus is a rare group of autoimmune diseases. It causes blisters on the skin and mucous membranes throughout the body. It can affect the mouth, nose, throat, eyes, and genitals. Pemphigus vulgaris is the most common type of pemphigus.
Pemphigus vulgaris. This type usually begins with blisters in your mouth and then on your skin or genital mucous membranes.
Pemphigus foliaceus. This type causes blisters on the chest, back and shoulders. The blisters tend to be more itchy than painful
Bullous pemphigoid is a rare skin condition that causes large, fluid-filled blisters. They develop on areas of skin that often flex — such as the lower abdomen, upper thighs or armpits. Bullous pemphigoid is most common in older adults and can be life threatening.
Autoimmune Thyroid Disease
In autoimmune thyroid disease, antibodies can occur against thyroid microsomes, mainly thyroperoxidase (TPO), and thyroglobulin (TG). Gluten has been implicated in autoimmune thyroid disease through molecular mimicry.
Hashimoto’s autoimmune thyroiditis (AIH) from autoimmune-mediated lymphocytic infiltration that leads to the destruction of the thyroid tissue and consequently reduced thyroid hormone production (hypothyroidism). Autoantibodies found can include anti-TPO (90% of cases), TSH receptor (TRab 6-60% of cases), and anti-TG (45-60% of cases)..
Grave’s disease – is autoimmune hyperthyroidism. TRab found in >90% of cases with high titres associated with severe disease; anti-TPO (80%), and anti-TG (30%) of cases.
Post-partum thyroiditis can also occur which usually resolves within 12-months post birth.
Neurological Diseases
Paraneoplastic Neurological Syndromes (PNS) are diseases of the central and peripheral nervous system, that occur in direct relation to tumour development (but are not caused by the tumour, or therapy).
Depending on the type of tumour, different intracellular antigens get expressed which can induce the formation of specific autoantibodies (Hu, Yo, Ma) etc
Autoimmune encephalopathies exhibit autoantibodies against neuronal cell surface antigens (glutamate receptors) – NMDA, AMPA, GABA B, DPPX, voltage gated potassium channels (VGKC) etc
Since these antigens play a role in synaptic signal transduction, the associated autoimmune conditions present clinically as seizures and neuropsychiatric symptoms.
Other types of autoimmune diseases can include Autoimmune Alopecia, Type 1 Diabetes, Psoriasis, Multiple Sclerosis, Addison's Disease, and many more. A Complete list of autoimmune diseases can be found here.
Whilst the trigger is often difficult to determine, there is evidence that autoimmunity can follow infection, but that more than one infection can initiate disease. Other environmental factors are also relevant but are not well defined and may include mercury, silica, smoking, pesticides etc.
Infections linked with Autoimmune Diseases
Bacterial infections potentially linked to autoimmune disease
Strep throat
Scarlet Fever
Food Poisoning
Lyme disease
Sexually transmitted infections potentially linked to autoimmune disease
Chlamydia
Hepatitis B
Herpes Simplex Virus 1
HIV
Viral infections potentially linked to autoimmune disease
Infectious Mononucleosis (EBV) - Glandular Fever
COVID-19 - recent studies have shown that infection may reactivate EBV in some people, and that EBV has been found to be linked to autoimmune disease.
Cytomegaloviris
Measles
German measles (Rubella)
Hand, foot, and mouth disease
Mumps
Influenza
Zika virus
West Nile virus
Chickenpox
Parvovirus B19
Rotavirus
Hepatitis A
Hepatitis C
Viral infections and Autoimmunity
Viruses have unique ways in which they can cause autoimmune diseases which is not helpful to humans. In the graphic below we can see the mechanisms:
a. Following the steps around the first graphic - Viruses infect our cells. The viral antigens are presented to T-helper cells alerting the body we have an invader. The T-helper cells release cytokines which notify the cytotoxic T lymphocytes to release granzymes that are cell death inducing enzymes. This enables our bodies self-antigens to leak out and become another source of danger that the antigen presenting cells present to T cells for target. This unfortunately means other cells in our body that have these same leaked antigens can become targeted.
b. A process of molecular mimicry where T cell receptors recognise both viral antigens and self antigens that are structurally similar, and deal with them in the same toxic way.
c. Bystander activation whereby cells just being in close proximity to viral infected cells that are being targeted by the immune system, also get injured and die. The inflammation that happens around the cells after the attack also impacts on localised cells.
Immune Imbalance
Autoimmune Diseases can show imbalanced T helper 1 (Th1) or T helper 2 (Th2) cells.
Potential natural remedies to rebalance Th1 and Th2 cells
Th2 Stimulating Compounds
Green Tea, Resveratrol, Curcumin, Quercetin.
Th1 Stimulating Compounds
Echinacea, Astragalus, Licorice Root, Ashwaganda, Panax Ginseng, Mushrooms (Maitake, Reishi, Shiitake), Chlorella, Grape Seed Extract.
Autoimmune testing is complex. Ensuring you are having the results interpreted by someone qualified who really understands the complexities of your health journey is important. I have worked in the autoimmunity sector for a large part of my career meaning I am qualified to assist you. If you would like to discuss your own personal autoimmunity concerns, and understand potential causations, then please don't hesitate to make a booking with me.
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References:
Multiple early factors anticipate post acute COVID-19 sequelae
Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation
Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity
The Role of Viral Infection in the Onset of Autoimmune Disease
Viral reactivations and co-infections in COVID-19 patients: a systematic review
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