Normal Function
The HLA-DRB1 gene provides instructions for making a protein that plays a critical role in the immune system. The HLA-DRB1 gene is part of the human leukocyte antigen (HLA) complex. HLA complex genes help the immune system distinguish between the body's own proteins and the proteins made by foreign invaders, such as viruses and bacteria.
The protein produced from the HLA-DRB1 gene, called the beta chain, binds to another protein (the alpha chain), which is produced from the HLA-DRA gene. Together, they form a larger protein called the HLA-DR antigen-binding heterodimer. This protein binds to protein fragments (peptides) that are outside the cell and presents them to the immune system. If the immune system recognizes the peptides as foreign, it triggers a response to attack the invading viruses or bacteria.
The wide variety of HLA genes allows the immune system to respond to a range of foreign invaders. There are also many different versions of each HLA gene. Different versions of a gene are called alleles. Researchers have identified hundreds of alleles of the HLA-DRB1 gene, each of which is assigned a specific number (such as HLA-DRB1*04:01).
Health Conditions Related to Genetic Changes
Autoimmune Addison disease
Certain HLA-DRB1 alleles have been linked to an increased risk of developing an autoimmune disorder called autoimmune Addison disease. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs.
Normally, the immune system responds only to proteins made by foreign invaders, not to the body's own proteins. In people with autoimmune Addison disease, however, an immune response is triggered by a protein made by the small, hormone-producing glands that are located on top of each kidney (adrenal glands). In about 85 percent of people with autoimmune Addison disease, the trigger protein is 21-hydroxylase. 21-hydroxylase plays a key role in producing a variety of hormones that regulate many essential body functions.
The prolonged immune attack that is triggered by 21-hydroxylase damages the adrenal glands' outer layer, preventing hormone production. A shortage of adrenal hormones (adrenal insufficiency) disrupts several normal functions in the body, leading to the diverse features of autoimmune Addison disease. These include extreme tiredness (fatigue); nausea; low blood pressure (hypotension); and abnormally dark areas of skin (hyperpigmentation), especially in regions that experience a lot of friction such as the armpits, elbows, and knuckles.
A particular HLA-DRB1 allele, HLA-DRB1*04:04, is the best-known risk factor for developing autoimmune Addison disease; however, it is not clear exactly how HLA-DRB1*04:04 and other HLA-DRB1 alleles are involved in the inappropriate immune response that causes autoimmune Addison disease.
More About This Health ConditionMultiple sclerosis
Certain HLA-DRB1 alleles have been associated with multiple sclerosis (MS). This condition is characterized by areas of damage (lesions) in the brain and spinal cord. Affected individuals may exhibit a variety of signs and symptoms, including problems with coordination, walking, speech, and vision.
Some HLA-DRB1 alleles increase the risk of developing MS, while others seem to protect against it. One HLA-DRB1 allele, HLA-DRB1*15:01, has been associated with an increased risk of developing MS. It is unclear exactly what role the different HLA-DRB1 alleles play in the development of multiple sclerosis. A combination of genetic, environmental, and lifestyle factors is likely involved in causing this condition.
More About This Health ConditionRheumatoid arthritis
Several HLA-DRB1 alleles are associated with a person's risk of developing rheumatoid arthritis. This disease causes chronic inflammation that primarily affects the joints. HLA-DRB1 is one of several genes in the HLA complex that have been associated with rheumatoid arthritis; variations in this gene are the most significant known genetic risk factor for developing the disease.
Two HLA-DRB1 alleles, HLA-DRB1*04 and HLA-DRB1*01, are strongly associated with a high risk of developing rheumatoid arthritis. These alleles lead to the production of beta chains that often contain a specific sequence of protein building blocks (amino acids) called the shared epitope. These alleles alter the part of the protein that binds to viral or bacterial peptides. This binding normally triggers the immune response that attacks foreign invaders. Changes in the beta chain caused by the shared epitope make the protein more likely to bind to the body's own proteins, leading to an abnormal immune response.
While changes in the HLA-DRB1 gene can influence the risk of developing rheumatoid arthritis, many other genetic and environmental factors also contribute to a person's overall risk of developing this condition.
A few HLA-DRB1 alleles appear to reduce the risk of developing rheumatoid arthritis. It is unclear why these particular alleles may prevent the development of this condition.
More About This Health ConditionType 1 diabetes
Certain HLA-DRB1 alleles can affect the risk of developing type 1 diabetes. Type 1 diabetes is characterized by high levels of blood glucose, also called blood sugar, due to a shortage of the hormone insulin. Type 1 diabetes is caused by autoimmune damage to insulin-producing cells in the pancreas.
The risk of developing type 1 diabetes is strongly influenced by specific combinations of the HLA-DRB1 gene with other HLA genes called HLA-DQA1 and HLA-DQB1. Combinations of HLA alleles are called HLA haplotypes. One haplotype, written as DRB1*03:01-DQA1*05:01-DQB1*02, is called DR3. The other haplotype, written as DRB1*04:01/02/04/05/08-DQA1*03:01-DQB1*02, is called DR4. People with 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. Other HLA haplotypes only mildly increase the risk of type 1 diabetes, while some haplotypes seem to protect against it. Changes in other genes and environmental factors are also thought to affect the risk of developing type 1 diabetes.
More About This Health ConditionOther autoimmune disorders
Certain HLA-DRB1 alleles have been associated with many other autoimmune disorders, including pemphigus and sarcoidosis. Pemphigus is a condition that causes severe blistering of the skin and mucous membranes, such as the moist lining of the mouth. Sarcoidosis is a disorder that is characterized by inflammation in many organs and tissues of the body.
It is unclear how the different HLA-DRB1 alleles influence the risk of developing these autoimmune disorders. These disorders typically result from a combination of multiple environmental and genetic factors. Changes in other HLA and non-HLA genes also likely contribute to the risk of developing these complex conditions.
Alopecia areata
MedlinePlus Genetics provides information about Alopecia areata
More About This Health ConditionCrohn's disease
MedlinePlus Genetics provides information about Crohn's disease
More About This Health ConditionGraves' disease
MedlinePlus Genetics provides information about Graves' disease
More About This Health ConditionHashimoto's disease
MedlinePlus Genetics provides information about Hashimoto's disease
More About This Health ConditionIdiopathic inflammatory myopathy
MedlinePlus Genetics provides information about Idiopathic inflammatory myopathy
More About This Health ConditionIdiopathic pulmonary fibrosis
MedlinePlus Genetics provides information about Idiopathic pulmonary fibrosis
More About This Health ConditionJuvenile idiopathic arthritis
MedlinePlus Genetics provides information about Juvenile idiopathic arthritis
More About This Health ConditionLyme disease
MedlinePlus Genetics provides information about Lyme disease
More About This Health ConditionNarcolepsy
MedlinePlus Genetics provides information about Narcolepsy
More About This Health ConditionPsoriatic arthritis
MedlinePlus Genetics provides information about Psoriatic arthritis
More About This Health ConditionOther Names for This Gene
- major histocompatibility complex, class II, DR beta-1
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
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