World Ankylosing Spondylitis Day: A Gene Increases Risk Of The Disease. Experts Explain How

Ankylosing spondylitis is caused by a combination of environmental and genetic factors, the HLA-B27 gene playing a significant role in increasing the risk of the disease. 

Ankylosing spondylitis is a form of painful, ongoing joint inflammation, or chronic inflammatory arthritis and an autoimmune disease that causes inflammatory lower back pain, and eventually impairs spinal mobility severely due to structural changes leading to spinal fusion. 

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World Ankylosing Spondylitis Day is observed annually on the first Saturday of every May, with the aim to spread awareness about ankylosing spondylitis, and encourage people to take action toward its prevention. Ankylosing spondylitis is a form of painful, ongoing joint inflammation, or chronic inflammatory arthritis and an autoimmune disease that causes inflammatory lower back pain, and eventually impairs spinal mobility severely due to structural changes leading to spinal fusion. 

Ankylosing spondylitis is caused by a combination of environmental and genetic factors, the HLA-B27 gene playing a significant role in increasing the risk of the disease. 

The disease mainly affects the spine, and is characterised by symptoms such as chronic back pain and stiffness. Early symptoms of the disease usually arrive between the ages of 15 and 30, according to the United States National Institutes of Health (NIH). People who lead a sedentary lifestyle experience more pain due to the disease compared to others, but can manage the symptoms through regular physical activity. 

The disease caused inflammation of the joints between the pelvic bones, also called the ilia, and the base of the spine, also called the sacrum. The joints between the ilia and the sacrum are called sacroiliac joints. Sacroiliitis is the inflammation of these joints, and gradually spreads to the joints between the vertebrae. The inflammation eventually involves the whole spine, and results in a condition known as spondylitis. 

When the vertebrae fuse together, back movement becomes limited. Ankylosis refers to the progressive bony fusion. Bones that become fused tend to fracture. 

When inflammation of tendon attachments to bones occurs, the condition is called enthesitis. About 20 per cent of patients who eventually develop ankylosing spondylitis when they grow up start suffering from enthesitis associated arthritis from childhood. 

Joints of the shoulders, hips, knees, and those between the spine and ribs can also be affected in people suffering from ankylosing spondylitis. When the joints between the spine and ribs are affected, people suffer from restricted movement of the chest, and this makes it difficult to breathe deeply. 

More about genetic factors responsible for ankylosing spondylitis 

Variations in several genes influence the risk of developing ankylosing spondylitis, according to NIH. The HLA-B gene, which is a part of a family of genes called the human leukocyte antigen complex (HLA), provides instructions for producing a protein that plays an important role in the immune system. 

The immune system is able to distinguish between the body's own proteins and proteins made by foreign invaders such as viruses and bacteria with the help of several structures, the HLA complex being one of them. 

There are different normal variations of the HLA-B gene, and each of them allows a person's immune system to react to a wide range of foreign invaders. The HLA-B27 gene is a normal variant of the HLA-B gene, and significantly increases the risk of developing ankylosing spondylitis. 

Experts claim that the HLA-B27 gene can create a protein that causes an aberrant immune response, resulting in ankylosing spondylitis, which is associated with inflammation and tissue destruction of the joints and spine. The environment in which a person lives can also play a role in influencing the development of the disease.

“The immune system's capacity to identify and distinguish between self- and non-self cells is influenced by the HLA-B27 gene. The HLA-B27 gene is thought to create a protein in persons with ankylosing spondylitis that causes an aberrant immune response, which results in inflammation and tissue destruction of the joints and spine. The environment may have additional effects on this process. Although not everyone with the HLA-B27 gene will experience ankylosing spondylitis, those who do are at significantly higher risk,” Dr Ravindra Srivastava, Director, Neurosciences, Primus Super Speciality Hospital, New Delhi, told ABP Live.

According to experts, 80 to 90 per cent of patients with ankylosing spondylitis are HLA-B27 positive, and the prevalence of ankylosing spondylitis mirrors that of HLA-B27 in different populations. 

Ankylosing spondylitis patients with the HLA-B27 gene have a 50 per cent chance of passing on the variant to their offspring.

“The HLA-B gene plays a vital role in the functioning of the immune system. It encodes a protein that resides on the surface of cells and helps in distinguishing between self and non-self proteins, such as those from viruses and bacteria. HLA-B has numerous variants designated by different numbers, and HLA-B27 is associated with ankylosing spondylitis. In some populations, 80-90% of ankylosing spondylitis patients are HLA-B27 positive, and the prevalence of ankylosing spondylitis mirrors that of HLA-B27 in different populations. The exact mechanism by which HLA-B27 contributes to ankylosing spondylitis pathogenesis remains unclear, but several theories have been suggested and extensively studied,” Dr. Harpreet Singh, Spine Surgeon, Regency Hospitals, Kanpur, told ABP Live.

Dr Singh also said that ankylosing spondylitis tends to be hereditary, and the HLA-B27 gene variant can be passed on from a family member. “If an individual with ankylosing spondylitis tests positive for the HLA-B27 gene variant, there is a 50% chance of passing on the variant to their children. It is estimated that 5-10% of children who inherit this gene variant will eventually develop ankylosing spondylitis.”

People who have tested positive for the HLA-B27 gene have a seven to 10 per cent chance of catching ankylosing spondylitis, according to experts. 

“The HLA-B27 gene is common among people suffering from certain types of arthritis and inflammatory disease. Not everyone with the gene can face ankylosing spondylitis. However, people who tested positive for this gene have a 7-10% chance of catching ankylosing spondylitis. This is an auto-immune disease that restricts the body's movements. The body acts inappropriately on the tissues. One of the major reasons for this is the HLA-B27 gene. In severe conditions, the body forms new bones to heal from within. There is fusion created in the sections of the vertebrae and it further can stiffen the rib cage restricting lung capacity and function,” Dr Amit Deshpande, Founder & Director, Activist, told ABP Live.

Some experts state that the presence of HLA-B27 is not a cause for worry because the majority of the people who test positive for the gene never develop the disease.

“There is a genetic predisposition to ankylosing spondylitis and it is manifested through the HLA-B27 gene. HLA-B27 is strongly associated with the development of ankylosing spondylitis. While amongst patients with ankylosing spondylitis, 80-90% are positive for HLA-B27, the majority of people who are HLA-B27 positive will never develop ankylosing spondylitis,” Dr. Suma Balan, Consultant Paediatric Rheumatologist, Rheumatology and Clinical Immunology, Amrita Hospital, Kochi, told ABP Live.

Dr Balan concluded that in the absence of the clinical context of an arthritic disorder that is attributable to ankylosing spondylitis, the presence of the HLA-B27 gene is not a cause for worry.

Other genetic factors associated with an increased risk of ankylosing spondylitis include variations in genes such as ERAP1, IL1A, and IL23R, which play important rules in the immune system.