By Dr Ananya Mandal, MD
The cause of ankylosing spondylitis is not clearly understood. However, a genetic association is clear. Pathogenesis of this condition has clear associations with the HLA-B27 gene.
The HLA-B27 gene
Persons who suffer from ankylosing spondylitis seem to carry a particular gene known as human leukocyte antigen B27 (HLA-B27).
Nearly 90% of individuals with the condition test positive for this gene. However, having the gene along may not predict with 100% certainty that a person with get the disease.
Around 8% individuals in the general population have the HLA-B27 gene but do not have ankylosing spondylitis.
Persons who have a close relative who has ankylosing spondylitis, such as a parent or a sibling, the risk of developing ankylosing spondylitis is increased. This again could be due to presence of the HLA-B27 gene.
Underlying mechanisms of ankylosing spondylitis
There are no single agents that have been associated with the causation of ankylosing spondylitis. There seems to be a complex interaction between raised serum levels of IgA (Immunoglobulin A) and acute phase reactants of inflammation, the body’s immune system and the HLA-B27 gene.
A typical histological finding is called Enthesitis. Enthesis is the insertion of a tendon, ligament, capsule, or fascia into bone. Typically in anklylosing spondylitis this enthesis is inflamed at the vertebrae.
Studies show that the entheseal ﬁbrocartilage is the major target of the immune system and inflammation in ankylosing spondylitis. Enthesitis was originally considered as the hallmark of ankylosing spondylitis.
In addition, there is seen to be mild and destructive synovitis or inflammation of the synovium that forms a cushion in the joints. The myxoid subchondral bone marrow is also affected.
As the disease progresses it destroys the nearby articular tissues or joint tissues. The original and new cartilages are replaced by bone through fusion. This causes fusion or joining up of the joint bones and stiffness and immobility. This is the hallmark symptom in the spine in ankylosing spondylitis.
Genetic and environmental factors
There is probably an interaction between the class I MHC molecule HLA-B27 and the T cell immune response. The HLAB27 presents an antigen to the CD8+ T cells and this in turn activates the immune system to attack the ﬁbrocartilage or cartilage.
Bacterial infections are suggested to be triggering events in some cases and thus the environment may also play a part. Patients with the condition also have a higher production of IL10 (Interleukin 10) by CD8+ T cells. They have low levels of TNFα and interferon.
Reviewed by April Cashin-Garbutt, BA Hons (Cantab)