Ankylosing Spondylitis in a Nutshell

By Teri Salisbury

Ankylosing Spondylitis (AS) is not a commonly known or understood disease. Attempting to define it is both simple and complex. Basically, it is a form of chronic autoimmune / auto-inflammatory disease, affecting the spine and large joints. In reality, it can affect any joint, large or small. AS is a form of inflammatory arthritis, without the rheumatoid factor. As inflammation (spondylitis) spreads, and the disease progresses, back movement can become more painful. The vertebrae in the spine, over time, may fuse together. This fusion is called ankylosis. Fusion of vertebrae can cause severe spinal deformation. [12,21,40]

The exact cause of Ankylosing Spondylitis is not known. Gender, age, and heredity are the few known risk factors. AS is approximately three times more prevalent in men and tends to strike most often between the ages of 17 and 34. A majority (90%) of the people who have AS also have the Human Leukocyte Antigen (HLA)-B27 gene. The presence of this gene is not an indicator that a person will get AS, as a majority of people with this gene never develop AS.[27]

The human leukocyte antigen system is located in chromosome 6. [14]  These genes are unique to the individual.  In clinical situations, HLA typing (matching) is necessary to determine compatibility between a transplant donor and receiver.[49]  The main job of the HLA system is regulating the body’s immune response. [2]   Science has yet to fully understand exactly what part the HLA-B27 gene plays in developing AS and scientists continue to try to unravel this mystery. [12,26,27]

Although AS is a skeletal disease, there are a number of conditions that are associated with it.  The manifestation of these conditions is unique to the individual. They range from “rarely occur” to “commonly occur.”  Some of these conditions can be severe and possibly fatal.

Conditions Associated with Ankylosing Spondylitis

AS is progressive. Damage to joints is irreversible. It can affect any joint in the body as well as produce a variety of conditions, including:

  • Back pain and morning stiffness. [21,5]
  • Sacroiliitis, which may feel like a nonspecific pain in the buttocks. [37]
  • Small joints may redden, swell and appear deformed. [35]
  • Severe skin rashes. [7]
  • Severe chronic fatigue. [41]
  • Insomnia. [41]
  • Anterior Uveitis.  This condition can cause blindness. [43,50]
  • Muscle spasms. [5]
  • Inflammation where tendons and ligaments attach to bones. [18]
  • Plantar fasciitis, inflammation in tissues on the bottom of feet. [5]
  • Leakage of the aortic valve. [5]
  • Restrictive lung disease and apical lung fibroids. [41]
  • Ulcerative Colitis, inflammation of the large intestine or colon. [41]
  • Crohn’s disease, inflammation of the digestive tract. [41]
  • Congestive heart failure. [9]
  • Mouth sores and fever blisters. [41]
  • Depression – increased chance. [33]
  • Anxiety and stress. [18]
  • Subclinical gut inflammation. [42]
  • Food sensitivity. [18]
  • Inflammation can affect any organ, any tendon, ligament, or joint. [5]

The Immune System and AS

The Human Leukocyte Antigen complex assists the immune system in determining if the proteins on the surface of cells indicate an invader cell or a cell that is part of the host body.  It is thought that the ability of the immune system to distinguish between foreign invader cells and the host cells is broken in some people that are HLA-B27 positive, causing the immune system to mistakenly attack healthy cells of the host.  Anti-inflammatory drugs, Immunosuppression drugs, and biologics that interact with the immune system on a cellular level are some of the treatment options used in managing AS. [27]

Researchers have determined that CD4+ T helper 17 cells that, when stimulated by an antigen, produce a specific cluster of cytokines, which include interleukin -17A (IL-17A) and IL-17F, which are pro-inflammatory cytokines. [1,2,44,46]  An over production of these cytokines can cause the development of autoimmune diseases, [45] one of which is AS.  What this means is that the pro-inflammatory cytokines are over producing and attacking host cells as though they are foreign invader cells. [54]

In a normal immune system, during an infection, cells produce IL-10 anti-inflammatory cytokines.  These cytokines inhibit the production of pro-inflammatory cytokines to maintain the appropriate level of inflammation.  In the case of autoimmune disease, there is no infection, so cells are not stimulated into producing IL-10 cytokines. The lack of balance causes inflammation to rage out of control.

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