Genetic Susceptibilities of Autoimmune Disease
As you read this blog, you’ll see many contributing factors linked to autoimmune disease. The one common trend is these factors especially affect those that are “genetically susceptible”. All that means, is certain individuals are born with genetic abnormalities that interfere with our normal built-in protect mechanism and leave them more predisposed to autoimmune disease.
Autoimmune Disease Runs in Families
Clinical and epidemiological evidence shows autoimmune disease tends to be inherited and run in families. Close relatives are more likely to develop the same or related autoimmune disease. The reason: genes play important roles [1].
Genes
Genes work to encode various proteins. Some of these proteins work within the immune system. We understand there are a number of factors contributing to autoimmune disease including alterations to antigen presentation, type 1 interferon, Toll-like receptor and NF-Kb signal, B-cell and T-cell function, apoptosis, clearance of cellular debris and immune complexes [2], all of which our genes control.
Histocompatibility Complex HLA
On the short arm of chromosome 6 is a complex known as Human Leukoctye antigen (HLA) system. HLA genes are transmitted to children from their parents [2]. People with certain HLA genotypes are at increased risk of developing autoimmune disease.
There are 2 classes of HLA Genes – Class I and Class II.
Class 1 molecules are HLA-A, HLA-A, HLA-B, HLA-C. These molecules are recognized by CD8+ T cells and Natural Killer (NK) cells [2].
Class 2 molecules are HLA-D, which are subdivided into HLA-DP, HLA-DQ and HLA-DR subregions. These cells are subdivided into CD4+ T-cells [2].
HLA Disease Associations
As mentioned above, certain HLA genes are associated with specific autoimmune disease.
Individuals with the following genetic representations are at increased risk of developing the following conditions: [2] [1].
- Class 1
- HLA-A: Multiple Sclerosis
- HLA-A3: Hemochromatosis
- HLA-B27: Ankylosing spondylitis, Reactive Arthritis (Reiter syndrome), postinfectious arthritis, autoimmune uveitis
- HLA-BW47: 21-Hydroxylase deficiency (also lack HLA-B8)
- Class II
- HLA-DR2: Multiple sclerosis
- HLA-DR3: Graves disease, systemic lupus erythematosus
- HLA-DR4: Rheumatoid arthritis
- HLA-DR3/DR4: Type I diabetes mellitus
- HLA-DR5: Hashimoto thyroiditis
- HLA-DQ2: Celiac disease
- HLA-DQB1: Guillain-Barré syndrome, Multiple Sclerosis
Sometimes genetic under-representation can be associated with disease too.
- HLA-DRB13: Systemic lupus erythematous, Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, Systemic Sclerosis, Multipl Sclerosis, Myasthenia Gravis [3]
- HLA-B8: 21-Hydroxylase deficiency (also lack)
HLA and Gender Associations
HLA Class I and the related diseases are more common in men than women.
HLA Class II and the related diseases are more common in women than men.
Why Test Genetics?
Diagnosis
There are many cases where autoimmune disease is diagnosed based on a persons genetic testing. An example will be a patient experiencing sudden onset, new symptoms without known origin. Identifying genetic susceptibilities will help pinpoint disease processes.
Prevention and Better Understanding
Knowing which genetic markers a person has allows for more careful planning in the future. I’m able to educate my patients on the other autoimmune conditions associated with their HLA-type. I train them to identify the signs and symptoms of other diseases just so they can be more diligent and watch out for other conditions.
Also, we now know certain environmental factors, including specific bacteria and viruses, which can turn these genes on and off. That too makes it more important for patients to be extra diligent in treating every-day infections – as these ordinary illnesses can trigger an autoimmune disease.
Review
As you can see, genetics are important factors in autoimmune disease. Furthermore, specific markers such as the HLA genotypes are especially significant because they predispose an individual to certain autoimmune diseases.
Understanding this info empowers a patient to not only understand their current autoimmune disease, but it also allows them to take extra precautions knowing what other autoimmune diseases they may be more susceptible to.
