PTPN22 and Autoimmune Diseases

Key takeaways:
~ The PTPN22 gene helps in regulating the immune system, particularly by controlling the activation of T cells and B cells. This helps keep the immune response in check.
~ Genetic variants in the PTPN22 gene are linked to a wide range of autoimmune conditions, such as vitiligo, alopecia areata, thyroid diseases, and juvenile arthritis.
~ Environmental factors and other genetic influences also play important roles.

PTPN22: Genetics and Autoimmune Diseases

Genome-wide association studies allow researchers to cast a wide net, searching for genetic variations that increase susceptibility to diseases or conditions. One of the first autoimmune-related variants that genetic researchers discovered is in the PTPN22 gene (protein-tyrosine phosphatase nonreceptor 22).

This unexpected discovery left researchers searching for the answer to ‘why PTPN22?'[ref][ref]

Subsequent research shows that PTPN22 regulates the immune system by impacting T cell activation and B cell auto-reactivity. It acts as a negative regulator, dampening T cell activation. Additionally, PTPN22 impacts innate immunity by promoting interferon I production.[ref][ref][ref]

A balancing act between killing invaders and not hurting your own cells.

The body produces T-cells and B-cells as part of the immune system. These are the cell types that recognize danger (e.g., bacteria, viruses) and identify non-danger (e.g., your own cells).

B cells (aka B lymphocytes) are a type of white blood cell that secretes antibodies and also presents antigens. T cells, similarly, are a type of white blood cell that matures in the thymus and controls the immune response. Both B and T cells perform important immune system functions for determining invaders and keeping immune response in check against ‘self’.

Variants in the PTPN22 gene change the way that it functions, causing an increase in the inhibitory function of B-cells.[ref][ref]

The PTPN22 variants are linked to autoimmune diseases that affect connective tissues, the thyroid, joints, muscles, blood, and the pancreas. But the variants don’t seem to increase the risk of autoimmune diseases that target the eyes, gastrointestinal tract, or brain. PTPN22 genetic changes are linked to:[ref][ref][ref]

• Rheumatoid arthritis
• Vitiligo
• Alopecia areata
• Vasculitis
• Autoimmune Addison Disease
• Graves’ Disease
• Hashimoto thyroiditis
• Idiopathic inflammatory myopathy
• Juvenile arthritis
• Lupus
• Systemic scleroderma
• Type 1 diabetes
• Myasthenia gravis
• Allergic rhinitis

What if you don’t have an autoimmune disease?

Research shows that even people without autoimmune diseases have a change from the PTPN22 R620W variant. People with even one copy of the variant have increased autoreactive B cells and autoantibodies.[ref]

Trade-offs:

Recent work using transgenic mice points to the PTPN22 variant that increases autoimmune risk by possibly decreasing skin cancer risk and improving survival in other cancers.[ref]

Additionally, research seems to show that people with the PTPN22 variants are at a decreased risk of Crohn’s disease and Behçet’s disease.[ref]

Quick Recap Table: PTPN22 and Autoimmunity

Making Connections:

PTPN22 plays a role in susceptibility to autoimmune conditions, but it is just part of the picture. Genetic variants in PTPN22 combine with other genetic variants and environmental factors.

Meniere’s Disease causes vertigo and tinnitus. PTPN22 can play a role in susceptibility, but other genes are also important.

Thyroid conditions can have an autoimmune component. Learn more about the genetic variants that increase susceptibility to Hashimoto’s and to Graves’ disease.

Inflammatory bowel diseases (IBD) include Crohn’s and ulcerative colitis. PTPN22 may increase the relative risk along with NOD2 gene mutations.

Psoriasis is another autoimmune disease that includes PTPN22 as just one of the genetic risk factors.

Lupus is a complex autoimmune disease with many different genetic susceptibility variants, including PTPN22.