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  Sep 30, 2018

Autoimmunity Genetic Factors

Autoimmune conditions are multifactorial in their cause, with a mixture of genetic and environmental factors often playing a role.

As multifactorial conditions are partly caused by genetic factors, autoimmune conditions tend to run in families. Environmental factors such as viruses or sunlight then trigger an immune response in genetically susceptible individuals.

When one individual in a family has an autoimmune condition, other family members are then at an increased risk of autoimmunity. However, genetically susceptible individuals do not always go on to develop an autoimmune condition.

There are three main groups of genes that are thought to raise the risk of autoimmune diseases developing. These genes are associated with T cell receptors, immunoglobulins and the major histocompatibility complexes. T cell receptors and immunoglobulins are important for the recognition of antigens and are highly variable to allow for the massive variation in antigens that the immune system needs to be able to target. However, this number of variations can also give rise to the development of lymphocytes that are capable of autoreactivity.
 

Over the years, various researchers such as McDevitt, Nepom, Bell and Todd have provided evidence suggesting that some MHC class II allotypes are strongly associated with certain conditions. Examples include:

  • HLA DR2 is positively associated with Systemic Lupus Erythematosus (SLE), multiple sclerosis and narcolepsy, while it is inversely associated with type I diabetes mellitus.
  • HLA DR3 is strongly associated with myasthenia gravis, SLE, type I diabetes and Sjögren's syndrome.
  • HLA DR4 is strongly associated with Type 1 diabetes mellitus, pemphigus vulgaris and rheumatoid arthritis.

Correlations between autoimmune conditions and MHC class I molecules are less common, but one notable example is the association between ankylosing spondylitis and HLA B27.

In terms of genes that exist outside of the MHC complex, genes that contribute to the development of autoimmunity are currently being investigated in animal models of diabetes and SLE. One recent development is that the PTPN22 gene, which codes for protein tyrosine phosphatase, non-receptor type 22, is associated with various different autoimmune conditions including SLE, rheumatoid arthritis, type 1 diabetes, vitiligo, psoriatic arthritis and Grave’s disease.