SNP Highlight - PTPN22, Inflammation and Autoimmune Disorders

PTPN22, Inflammation and Autoimmune Disorders

Inflammation

Inflammation is a natural process that helps to protect the body as well as direct the body’s healing after an injury or infection. Inflammation at the most basic level is the white blood cells in the body releasing chemicals, such as cytokines, to attack potentially harmful organisms or to destroy and remove damaged tissue. This can occur locally, such as directed towards a specific part of the body, or this can occur systemically, such as when these chemicals are released into the bloodstream and are able to travel throughout the body. Side effects of inflammation include redness or warmth as well as swelling and pain. Normally, inflammation is short-lived and only lasts hours to a few days. When inflammation extends beyond this normal period the risk of chronic inflammation greatly increases. 

Chronic Inflammation

Chronic inflammation happens when the body experiences a prolonged immune response which signals the ongoing release of antibodies and proteins. This can lead to an overproduction of immune signaling molecules which can lead to serious health consequences. Unlike acute inflammation, the signs of chronic inflammation are not as noticeable and are usually harder to diagnose. Signs and symptoms of chronic inflammation include low-grade fevers, fatigue, localized or general pain, unhealing sores, and rashes. These symptoms can be mild to severe and last for weeks, months, or years. One of the major underlying factors of chronic inflammation is autoimmune disorders. However, while elevated levels of inflammatory molecules are a marker of both chronic inflammation and autoimmune disorders, a person can have chronic inflammation even in the absence of an autoimmune disorder. 

Autoimmune Disease and The Inflammatory Response

While the function of the immune response is to identify harmful pathogens or foreign molecules (antigens) in the body, it can sometimes mistake the body’s own cells and tissue as antigens resulting in the destruction of healthy cells and tissues. The term for the immune system attacking the body’s own structures is called autoimmune disease. Autoimmune disease is a condition that includes over 100 conditions including Celiac disease, Type 1 Diabetes, Lupus, Rheumatoid arthritis, Grave’s Disease, Juvenile Arthritis, Addison's Disease, Hypocortisolism, and Hashimoto’s Disease (1). While the exact mechanism that underlies autoimmune diseases is unclear, research has demonstrated that multiple factors interact to contribute to the onset and development of autoimmune pathologies including genetics, infections, lifestyle, stress, diet, and environment (2, 3).

The Genetics of Autoimmune Diseases

One of the current models to explain the development of an autoimmune disease is that certain individuals are more susceptible due to genetic variations and that exposure to lifestyle or environmental factors may prompt the onset of an autoimmune disorder (4). This has been supported by both observational studies, which have shown that certain autoimmune diseases are more likely to be hereditary, as well as genome-wide association studies that link genetic variations with various autoimmune diseases (5). Furthermore, genes that are associated with autoimmune disorders are often implicated in multiple inflammatory pathways such as NF-kappaB signaling, regulation of T-cell activity, B-cell function, apoptosis, autophagy, and toll-like 1 receptor activity (6). 

One of the most studied groups of genes are those that encode proteins found on the cell surface that help the cell recognize foreign antigens. This group of genes is called the major histocompatibility complex (MHC). 

The PTPN22 Gene, Inflammation, and Autoimmune Disorders

Additionally, outside of the MHC group of genes, there is evidence that single nucleotide polymorphisms in the gene PTPN22 (protein tyrosine phosphorylase non-receptor 22) play a major role in an individual’s risk of being predisposed to infection, immune dysregulation, and autoimmune disorders (7). A single base-pair change resulting in an arginine amino acid instead of a tryptophan amino acid, is associated with Variants in the PTPN22 gene which lead to altered activity and have been associated with impaired immune system signaling and numerous autoimmune diseases including Lupus, Type 1 Diabetes (8), Rheumatoid Arthritis (9), Vitiligo (10), Grave’s disease (11), and Hashimoto's disease (12).

The PTPN22 gene, which encodes a lymphoid protein of the protein tyrosine phosphatase family, is expressed exclusively in immune cells. It functions as a regulator of signal transduction which is how signals are relayed from outside of the cell into the interior of the cell, and to the cell nucleus. Specifically, this protein acts as a regulator of the immune response through the dephosphorylation of white blood T cells (13, 14), activation of toll-like receptor 1 molecules (15), and induction of autophagy and pro-inflammatory cytokine expression (16). 

Dealing with Inflammation and Autoimmune Disorders

When dealing with high levels of inflammation, either acute or chronic, most therapies include rest, ice compresses, and over the counter ibuprofen or prescription steroids. In the case of autoimmune disorders, immunosuppressants or steroids, such as prednisone, are often prescribed. There are diet, lifestyle and nutrition supplementation steps that people can consider to support healing and decreasing levels of inflammation as well. These include an elimination diet to identify and remove any food allergens or sensitivities, consuming chlorella, cilantro, blueberries or spirulina which help with body remove heavy metals and toxins that contribute to inflammation, incorporating foods such as turmeric and omega-3 fatty fish into the diet to reduce inflammation, and engaging in exercise or mindful activities daily. Additionally, supplementing with vitamin D3, glutathione, zinc, and probiotics have also demonstrated significant benefits in those individuals with immune dysfunction and autoimmune disorders (17, 18, 19). 

Learn more about Toolbox Genomics Immune Panel.