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 a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.
The HLA complex is the human version of the major histocompatibility complex (MHC), a gene family that occurs in many species. The HLA-DRB1 gene belongs to a group of MHC genes called MHC class II. MHC class II genes provide instructions for making proteins that are present on the surface of certain immune system cells. These proteins attach to protein fragments (peptides) outside the cell. MHC class II proteins display these peptides to the immune system. If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it triggers a response to attack the invading viruses or bacteria.
The protein produced from the HLA-DRB1 gene, called the beta chain, attaches (binds) to another protein called the alpha chain, which is produced from the HLA-DRA gene. Together, they form a functional protein complex called the HLA-DR antigen-binding heterodimer. This complex displays foreign peptides to the immune system to trigger the body's immune response.
Each MHC class II gene has many possible variations, allowing the immune system to react to a wide range of foreign invaders. Researchers have identified hundreds of different versions (alleles) of the HLA-DRB1 gene, each of which is given a particular number (such as HLA-DRB1*04:01).
Several common variations of the HLA-DRB1 gene are associated with a person's risk of developing rheumatoid arthritis. This disease causes chronic abnormal 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 of this gene are the most significant known genetic risk factor for the disease.
The HLA-DRB1 gene variations associated with an increased risk of rheumatoid arthritis affect single protein building blocks (amino acids) in the beta chain. These changes occur near the antigen-recognizing binding groove, which is the part of the protein that attaches (binds) to viral or bacterial peptides. This binding triggers the immune response that attacks foreign invaders. Although the mechanism by which HLA-DRB1 gene variations increase the risk of rheumatoid arthritis is unclear, researchers suspect it is related to changes in peptide binding that stimulate an abnormal immune response. However, many other genetic and environmental factors also contribute to a person's overall risk of developing rheumatoid arthritis.
Since the majority of patients with CIRS have a combination of genetic sensitivity plus exposure to a complex aerosolic mixture of mycotoxins, spores, bacteria, microbial fragments, inflammagens, volatile organic compounds, and other molecular species, the majority of patients with type 3 Alzheimer’s disease and CIRS are likely to have an inhalational cause of Alzheimer’s disease (IAD).
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