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Overview Edit

Originating from the greek words angkylos meaning "bent" and spondylos meaning spinal vertebra, ankylosing spondylitis (AS) is characterized by chronic inflammation of the spine. Symptoms often develop gradually in late adolescence/early adulthood, usually before the age of 40. Some key symptoms include: [1]

  • Chronic back pain (>3 months)
  • AS
    Morning back stiffness that improves with exercise
  • Increased pain and stiffness with immobility
  • Feeling tired
  • Pain or swelling in other joints

The disease occurs five times more frequently in men than it does in women which makes it unique among other autoimmune diseases which generally have a much greater prevalence among women.

Basics of the Disease Edit

There is no one test to determine if someone has AS. A physician can diagnose it by analyzing your symptoms and doing a physical examination. If you have been diagnosed with AS, there are a few things that can be done to help minimize the negative effects the disease has on your everyday life: [1]

  • Don't smoke -- Smoking can cause breathing problems for people with AS
  • Exercise -- Exercising can help alleviate some joint stiffness
  • Sleep on a thin pillow -- A thin pillow will minimize head and neck problems

Influence of Single Nucleotide Polymorphisms (SNPs) on Phenotype Edit

AS is thought to be caused by a mutation that codes for the Human Leukocyte Histocompatability complex (HLA). HLA is a polypeptide molecule involved in the body's cellular immune response. When the body is invaded by bacterial or viral products, antigen presenting cells (APC) act to ingest these foreign products and degrade them through protelyosis. The degraded pepetide products of these foreign invaders can then be presented on an APC via a surface HLA molecule to T-cells. In essence, the HLA molecules present peptide products from intracellular proteolysis to T-cells. The T-cells (CD8+ and CD4+) can then act in an organized manner to recognize and destroy foreign cells with similar surface peptide products as well as activatating more inflammatory T-cells to trigger a strong immune response against the invader.

The genes for the HLA molecules are located on chromosome 6p21. Class 1 HLA molecules are expressed on all nucleated cells in the body and are composed of an alpha chain and B2 microglobin chain which can present foreign peptides to cytotoxic CD8+ T-cells. There are 3 Class I HLA genes (HLA-A, HLA-B, and HLA-C). Each human has 6 different HLA class 1 gene loci (3 from maternal and 3 from paternal which are codominantly expressed) with tons of variable alleles at each class 1 loci. Each allele differs in at least one single nucleotide polymorphism position (SNP). The reason for such high variablility is that the HLA molecules must be able to recognixe an almost infinite combination of possible foreign peptide motifs.

The presence of the HLA-B27 allele is highly linked with AS. The relative risk of developing AS in someone who carries the B27 allele is 87.4. In people who present with AS and clinical findings of uveitis or aoritis 100% have the HLA-B27 allele. Among Caucasians only 8-9% of the general population carries the B27 allele. However, among Caucasians with AS, greater than 90% have the HLA-B27 allele. This is highly suggestive that the HLA-B27 allele plays a role in triggering the autoimmune findings in AS. The prevalence of AS in the general population is 0.2%. Among people who are positive for HLA-B27 allele, 2% go on to develop AS. Therefore, presence of the HLA-B27 allele alone is not enough to cause AS but it increases the susceptibility and there may be specific SNPs within the allele that have not yet been recognized that lead to the development of AS. It may also be that the presence of the HLA-B27 allele causes a genetic susceptibility that when combined with an environmental exposure triggers the development of AS. [2]

John Burke's Likelihood of Developing AS Edit

Based on the genetic analysis from 23andme, it is highly unlikely that Dr. Burke will develop AS at this point in his life. His genome does not contain the characteristic SNPs of someone that has AS. Furthermore, AS often develops much earlier in life and he would currently be symptomatic. From his 23andme analysis Dr. Burke can certainly learn about the presence of specific genetic markers that could increase his likelihood of developing various diseases. However, it also important to realize when looking at a genetic analysis that each gene has variable penetrance so the presence of the gene or SNP alone does mean that a phenotypic disease will occur with known certainty.

References Edit

  1. 1.0 1.1 http://www.mayoclinic.org/diseases-conditions/ankylosing-spondylitis/basics/definition/con-20019766
  2. Janeway, Charles. Immunobiology: The Immune System in Health and Disease. New York: Garland Science, 2005. Print.