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HLA-B haplotype is a risk factor for the autoimmune disease ankylosing spondylitis, how strong is this...

HLA-B haplotype is a risk factor for the autoimmune disease ankylosing spondylitis, how strong is this disease correlation? Calculate the percentage of patients carrying this HLA-B haplotype

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Expert Solution

Major histocompatibility complex (MHC), group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances. MHC proteins are found in all higher vertebrates. In human beings the complex is also called the human leukocyte antigen (HLA) system and is controlled by genes located on chromosome 6.  It is important to know that HLA is inherited mostly in males as a set of the three HLA groups, A, B, DR. This set is known as a haplotype.

MHC molecules are important components of the immune system because they allow T lymphocytes to detect cells, such as macrophages, that have ingested infectious microorganisms. When a macrophage engulfs a microorganism, it partially digests it and displays peptide fragments of the microbe on its surface, bound to MHC molecules. The T lymphocyte recognizes the foreign fragment attached to the MHC molecule and binds to it, stimulating an immune response. The arthritogenic peptide hypothesis suggests that HLA-B27 has a unique ability to bind antigens from a microorganism that trigger a CD8 T-cell response that then cross-reacts with a HLA-B27/self-peptide pair. The molecular mimicry hypothesis suggests that cross reactivity between some bacterial antigens and self peptide can break tolerance and lead to autoimmunity.

Although the exact cause of ankylosing spondylitis (AS) is unknown,it is know that genetics play a key role in the disease. Most individuals who have AS also have a gene that produces a genetic marker, the protein HLAB27. The presence of HLA-B27 on your white blood cells can cause your immune system to attack those otherwise healthy cells.  When this occurs, it can result in an autoimmune disease or immune-mediated disease AS. This disease causes chronic inflammation or arthritis of the spine and other sites which leads to spinal deformity and immobility. If one is positive to HLAB-27 in blood test then he may have a higher-than-average risk of certain autoimmune disease, ankylosing spondylitis (AS).

Only 1 to 5% of HLAB27-positive individuals develop AS, which indicates that other genes must also be involved. HLAB27-positive relatives of AS patients have a recurrence risk of the disease 5.6 to 16 times greater than HLAB27-positive individuals in the general population. A major non-HLAB27 contribution to susceptibility to AS is suggested by the greater concordance rate of monozygotic twins (63%) than of HLAB27-positive dizygotic twin pairs (23%).


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