Sometimes, the immune system mistakes healthy parts of the body as invaders, like bacteria or viruses, and attacks them. In other words, the human body can attack itself in the same sense it would a pathogen. When the immune system attacks a pathogen, it’s protecting you against infectious illness. When the immune system attacks itself, it causes autoimmune disease but believes it’s acting in a protective manner.

Infectious disease and autoimmune disease share some similarities beyond this conceptual comparison. In fact, a multitude of viral infections, including COVID-19 and influenza, have been linked to autoimmunity. Infections (not just viral) are potential external triggers for autoimmunity. Bacterial infections, such as strep throat, scarlet fever, food poisoning, and Lyme disease, have also been linked to autoimmune disease. Sexually transmitted infections that have been linked to autoimmune disease include chlamydia, hepatitis B, herpes, and HIV. Nevertheless, just because you’ve had an infection, even one listed here, doesn’t mean you’ll develop an autoimmune disease. This is true even for those with a genetic predisposition.

Even though researchers have yet to definitively explain autoimmunity, it is known that a combination of genetic predisposition and external triggers contribute to the development of this type of illness. To help avoid triggering predisposition, GeneCompassTM assesses your genetic risk for developing some of the most common autoimmune diseases.

Autoimmune diseases are linked to genetics for several reasons:

• ●  Genomic research has identified specific genetic variants that are common in people with various autoimmune diseases.

• ●  Many autoimmune diseases run in families.

○ For example, a child’s risk of multiple sclerosis, a disease linked to a

HLA-DRB1 variation, increases from .1% to 2%–a 20-fold increase–when one parent has the disease. Other diseases, like psoriasis, can affect extended family members as opposed to only immediate ones.

● A large number of autoimmune diseases affect specific ethnic populations.
○ For example, type 1 diabetes is more common in white people, and lupus

is known to be more severe in African-American and Hispanic populations.

Autoimmune diseases share overlapping genetic causes. Patterns of inheritance aren’t limited to a certain genetic variant or a certain autoimmune disease. A shared underlying genetic factor can predispose a person to autoimmunity in general. This is why some with lupus report having a family member with rheumatoid arthritis and other autoimmune diseases unrelated to lupus itself. The co-occurence of diseases is also evident through shared variants; for example, type 1 diabetes and celiac disease share variants on the HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes. Because of instances in which someone has one of these variants but doesn’t develop more than one disease, this suggests that a person genetically predisposed to autoimmunity may only develop a

disease if exposed to an external trigger that, in a sense, flips the on-switch on the condition.

A Common (HLA) Genetic Thread Between Common Autoimmune Diseases, Rheumatoid Arthritis, Type 1 Diabetes, and Celiac Disease

When the body senses danger from an infection, the immune system kicks into gear and attacks it. This is called immune response. Sometimes healthy cells and tissues get caught up in this response, and many scientists believe this is what causes rheumatoid arthritis, an autoimmune disease that attacks joints and other tissues. Variations in dozens of genes have also been studied as risk factors for rheumatoid arthritis, identifying HLA (human leukocyte antigen genes) genetic variants as the most significant genetic risk factors, especially the HLA-DRB1 gene. The proteins that HLA genes produce help the immune system distinguish the body’s own proteins from those made by foreign invaders like viruses and bacteria.

The HLA-DRB1 gene is also linked to type 1 diabetes risk. Type 1 diabetes is characterized by a shortage of the hormone insulin caused by autoimmune damage to insulin-producing cells in the pancreas, which results in high blood sugar levels. Type 1 diabetes risk is most increased with two specific combinations of variations between HLA-DRB1 and other HLA genes, HLA-DQA1 and HLA-DQB1. People at the highest risk of developing type 1 diabetes have one copy of the DR3 haplotype and one copy of the DR4 haplotype in each cell (combinations of HLA genetic variants are called HLA haplotypes). Other HLA haplotypes only mildly increase risk for this disease while some others seem to be of protective risk, the genetic antonym of increased risk.

The impact of HLA genes and HLA-DRB1 specifically in the context of autoimmune disease spans beyond just rheumatoid arthritis and type 1 diabetes. The evidence and knowledge of the ties between these genes and these two autoimmune diseases is uniquely strong, which is why GeneCompass analyzes HLA-DRB1 for these diseases specifically and not others linked (such as Crohn's disease and Graves’ disease). However, the test does look for variants on HLA-DQB1 for both celiac disease and type 1 diabetes susceptibility.

Like HLA-DRB1, HLA-DQB1 provides instructions for making a protein critical to immune system function and helps the immune system differentiate between the body’s own proteins and that of foreign invaders. This is one of the genes with identified significance with type 1 diabetes. Just as the combination of specific HLA variants (haplotypes) increase risk for type 1 diabetes, the combination of two other haplotypes, DQ2 and DQ8, increases risk for celiac disease. These haplotypes are correlated with

an increased risk of inappropriate immune response to the protein gluten, which is found in wheat, rye, and barley. 3% of individuals with these genetic changes develop celiac disease despite 30% of the general population having DQ2 and DQ8 haplotypes in their DNA.

Navigating Autoimmunity

In some cases, you are simply predisposed to autoimmunity at birth–inevitably increasing your risk of developing an autoimmune disease. In other cases, autoimmune disease may be caused by conditions out-of-your control. For example, the Epstein-Barr virus (EBV) is closely linked to rheumatoid arthritis, type 1 diabetes, and celiac disease. EBV infections occur in more than 90% of the population, proving just how out-of-your control this autoimmune-linked infection is. Nevertheless, if you have a family history of autoimmune disease, making healthy lifestyle choices, like avoiding cigarettes and maintaining a healthy weight, can help mitigate risk. Auto-immunity very well may be the result of a “perfect storm” in which genetic and external factors work in tandem to turn that autoimmune switch on.

Autoimmunity is frustrating. It can be hard to diagnose and come across as an invisible illness to those around you despite your symptoms. GeneCompass is built to help you abbreviate the lengthy, perplexing odyssey that often comes with diagnosing autoimmune disease. GeneCompass assesses your susceptibility to Graves’ disease, Crohn’s disease, and Primary Sjögren’s Syndrome in addition to rheumatoid arthritis, type 1 diabetes, and celiac disease to help you navigate autoimmunity and guide you toward maintaining and boosting your immunity.