The exact cause of Ankylosing Spondylitis has not yet been specifically established. However, a genetic component seems to be particularly important. This relates to the presence of Human Leukocyte Antigen (HLA) B27 in a high proportion of patients with Ankylosing Spondylitis. HLA B27 is a protein that is present on the surface of certain cells, where it has an important role in the action of the immune system. The function of HLA B27 is to display antigenic peptides, which is in effect debris from oneself or from external insults (such as infection), to T cells that are very important in determining what immune response is necessary to these potential threats. The type of HLA present is genetically determined by chromosome 6.
HLA B27 is strongly associated with Ankylosing Spondyitis and to a lesser extent the other Spondyloarthritides. However, the exact mechanism relating HLA B27 with these diseases has not been determined. Although, interestingly, those who are HLA B27 positive are more likely to develop iritis, have an earlier onset of disease, and be diagnosed earlier with AS compared to their counterparts who are HLA B27 negative.
Nevertheless, this marker is present in 90-95% of those with AS, which is higher compared to those with Reactive arthritis, Enteropathic spondyloarthritis or Psoriatic spondyloarthritis where HLA B27 is present in 75%, 60%, and 50% respectively. The difficulty in understanding the role of HLA B27 is the fact that it is present in a significant proportion of the population who never develop an inflammatory spinal disease.
The prevalence of HLA B27 varies significantly, depending upon the population studied. In the Australian context, 8-12% of the population is HLA B27 positive, compared to 0.1-0.5% in the Japanese and up to 24% in the northern Scandinavian communities. It appears that the prevalence of HLA B27 in a community is related to the distance from the equator, with the highest rate furthest away such as in Northern Europeans with the least in sub-Saharan Africa.
However, as previously mentioned, the prevalence of AS in Australia is at most about 0.5%, highlighting that only a small proportion of those who are HLA B27 positive proceed on to develop the disease. That is, only 5-8% of those with HLA B27 will develop AS, so it seems that HLA B27 in itself is not the sole mediator in the development of the disease. As a result, the utility of testing for the presence of HLA B27 has been questioned, since neither a positive or negative test will be definitive in ruling the disease in or out. However, in a population with the early manifestations of an inflammatory spinal disease, assessing whether HLA B27 is present is thought to be useful and has therefore been included in the criteria for identifying axial Spondyloarthritis.
Although HLA B27 is the most important genetic aspect of the disease, there is active interest in other genetic factors. The most interesting of these identified at present is the Interleukin-1 (IL-1) gene cluster, which relates to a very important messenger that promotes inflammation called Interleukin-1. The CYP 2D6 gene is another genetic factor, but this seems to be only weakly associated with the disease.
Familial studies have confirmed the importance of genetics in the development of AS, since the risk of developing the disease is significantly increased if a first degree relative is affected. That risk has been estimated from 12-20%.
Although, the susceptibility for AS has a strong genetic component, other factors are necessary for the development of the disease. The nature of these other factors has not been definitively proven, but the most likely environmental agent thought responsible is infection. However, it is not known which specific infection triggers the onset of AS. The most likely culprit is either an intestinal or urinary pathogen (bacteria). The sexually transmitted infections, Chlamydia Trachomatis and Neiserria Gonorrhoeae are the common organisms responsible for Reactive arthritis, which is related to AS.
Therefore, the concluding remark regarding the cause of Ankylosing Spondylitis as we understand it at present is that it likely relates to an unknown environmental trigger, most likely an infection, occurring in a genetically predisposed host.
What is Ankylosing Spondylitis?
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