Ankylosing spondylitis Health Article

Definition

Ankylosing spondylitis (AS) is a relatively common disease that causes inflammation of the area where ligaments and tendons insert into the bone. The inflammatory process eventually leads to reduced mobility or immobility of affected joints. Specific joints are characteristically involved, notably in the spine and pelvis.

Description

Ankylosing spondylitis belongs to a group of disorders called the seronegative spondyloarthropathies. Each disease in this group is characterized by arthritis affecting the spine, as well as the absence of rheumatoid factor, a diagnostic marker that is present in rheumatoid arthritis and helps distinguish it from the group of diseases that includes AS. AS affects primarily the spine and the sacroiliac joint where the spine meets the hips. Progressive symptoms eventually result in fusion of these joints, pain, and markedly decreased joint mobility. AS is considered an autoimmune disease, meaning that symptoms are the result of the action of the immune system of the body against its own tissues. Although the exact mode of action is unknown, there is a strong association of AS with a specific type of human leukocyte antigen, HLAB27. HLA are genetically-determined proteins that play an important role in the functioning of the immune response of the body, in that they enable the immune system to distinguish between its own cells and foreign cells. Therefore, HLA type is important in immunity, as well as organ and tissue transplantation.

Genetic profile

AS is considered a multifactorial disorder, or one that is the result of both genetic and environmental factors interacting. Two genes have been identified that confer susceptibility to AS, both of which are forms of an HLA gene on chromosome 6. Some HLA types have been implicated in various autoimmune diseases, meaning diseases in which the immune system attacks the body's own cells and tissues.

The association of HLA B-27 and AS has been clearly established. Ninety-five percent of individuals with AS are B-27 positive, and since AS appears to be a dominant trait, the presence of at least one B-27 allele (a form of the gene) confers a greatly increased chance of developing symptoms. While this population risk may seem relatively high, it is important to realize that only about 9% of the population carries the B-27 allele. Of these individuals who are B-27 positive, only 2–8% will develop AS.

Other environmental and genetic factors most certainly contribute to development of the disease. This becomes more evident when considering that B-27 positive individuals with an affected first-degree relative have a significantly higher chance of developing AS than a B-27 positive individual with no family history. In families with multiple affected members, studies estimate that no more than half of AS recurrence is explained by HLA type. Additionally, there are several B-27 subtypes that have been studied; some confer susceptibility and some do not. Importantly, about 5% of people with AS are B-27 negative. Other environmental and/or genetic factors must certainly be associated with disease in these individuals. Another HLA type—B-60—has also been shown to confer susceptibility, although the association appears to be much weaker and is not seen in all studies. Certain infections are suspected as being necessary for triggering AS in some individuals. In the future, additional susceptibility genes and environmental factors can be expected to be identified.

Demographics

Approximately 0.25% to 1.5% of the population is affected with AS. Prevalence of the disease is comparable to the frequency of the HLA B-27 allele in the population, which varies among ethnic groups. Native North Americans, Alaskan Eskimos, and Norwegian Lapps all have relatively high levels of B-27 and AS. Low levels of B-27 and AS occur among individuals of most types of African ancestry, Australian aborigenes, and Native South Americans. Generally, for every affected female, there are 2-3 affected males.