Is Ankylosing Spondylitis an Autoimmune Disease?

Ankylosing Spondylitis Blurs the Line Between Autoimmune and Autoinflammatory Diseases

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Dan Brown

Ankylosing Spondylitis is a form of arthritis affecting the spine, primarily in men in their late teens or 20s. It is characterized by inflammation and can cause bones to overgrow and fuse together. The immune system undoubtedly plays a role in the development of the condition, but the question of which category it falls into – autoimmune or autoinflammatory – is the subject of some debate.

What is Ankylosing Spondylitis?

Ankylosing spondylitis (AS) is a form of arthritis that affects the spine. The word ‘ankylosing’ refers to the way bones may fuse together, while ‘spondylitis’ refers specifically to inflammation of the vertebra.

Stiffness and pain in the lower back is the most common symptom of ankylosing spondylitis, usually starting in one’s late teens or 20s and getting gradually worse over time. It can eventually lead to excess bone being formed and bones fusing together, which may cause inflexibility and a hunched posture in addition to stiffness and pain.

Many people with ankylosing spondylitis will also experience eye inflammation, thought to be because the antigen most associated with the condition, HLA-B27 (more on that later), is also linked to uveitis.

Given the typical age of onset, it is clear that ankylosing spondylitis is not a degenerative form of arthritis, such as osteoarthritis. Rather, the inflammation is almost certainly caused by something in the immune system going awry. So, is it an autoimmune disease like rheumatoid arthritis, or another form of immune-mediated disease?

Is Ankylosing Spondylitis an Autoimmune Disease?


There are three terms to consider here. Bearing in mind that there is no universal consensus regarding the definitions of these terms, and they are subject to evolve as we learn more about diseases of the immune system, they are:

  1. Immune-mediated inflammatory diseases
  2. Autoimmune diseases
  3. Autoinflammatory diseases

Here are brief summaries of what each means:

1. Immune-Mediated Inflammatory Diseases

This is a broad term, usually used to cover any diseases caused by some malfunction of the immune system that is characterized by inflammation (which is basically every immune-mediated disease, given then inflammation is central to the way in which the immune system operates).

Aside from indicating that the immune system is somehow involved, the term does not give much of a clue regarding the specific mechanisms of any given disease. It is useful as a kind of ‘catch-all’ term, as immune-mediated diseases often don’t fit into neat categories.

What’s more, immune-mediated diseases are extremely complex; researchers are yet to fully understand many aspects of the underlying mechanisms of such conditions. Diseases may be considered immune-mediated inflammatory diseases until more is known about them and a more precise title can be applied.

For some diseases, however, we know enough about what is going on to categorize them further.

2. Autoimmune Diseases

Although the terms immune-mediated inflammatory diseases and autoimmune diseases are often used interchangeably, the latter could be considered a more specific sub-category of the former.

Your immune system responds to foreign antigens, such as viruses and infections, by creating antibodies to fight them. It is known as its adaptive defense, as it responds to individual threats as they occur.

It takes the immune system a while (usually around two weeks) to produce effective antibodies, but their presence is long lasting (which is why you become immune to some viruses and infections after developing them once, and why vaccines protect you for years on end).

Most credible definitions of an autoimmune disease suggest that the body is attacking healthy cells in your body due to the presence of auto­antibodies. Autoantibodies target your body’s own cells and tissue due to the presence of auto­antigens, which your immune system identifies as foreign invaders.

Multiple sclerosis, type 1 diabetes, rheumatoid arthritis, and lupus are just a handful of known autoimmune diseases. While vastly different in terms of symptoms, autoantibodies have been identified for each of them. Similarly, the specific cells used by the adaptive immune system to carry out its job – T- and B-cells – can be identified and linked to specific autoimmune diseases.

It is not known exactly what causes autoimmune diseases to occur, but a combination of genetic and environmental factors appears to determine one’s risk, while viruses and infections may act as triggers.

Other posts you may be interested in on the MyTherapy blog:

3. Autoinflammatory Diseases

Whereas autoimmune diseases have been linked primarily to the immune system’s adaptive defense, autoinflammatory diseases are more commonly associated with its innate defense.

It is considered to be the immune system’s first line of defense and includes physical barriers such as your skin, body hair, and gastrointestinal and respiratory tracts; fluids such as mucous, gastric acid, and saliva; and general immune responses such as inflammation.

The innate immune also system triggers the adaptive defense into action when required.

The strength of the innate immune system is that it is able to respond immediately once a threat has been identified and offers general (or non-specific) protection against antigens.

The term ‘autoinflammatory disease’ was only coined around 20 years ago, in order to categorize diseases that are characterized by the innate immune system mistakenly attacking the body and causing inflammation. They are believed to be caused by mutations to genes that play a role in regulating the innate immune system.

Because autoinflammatory diseases are widely considered to be related to the innate arm of the immune system, the absence of autoantibodies (and autoantigen-specific T- and B-cells) is a key difference between them and autoimmune diseases.

Ankylosing Spondylitis: Autoimmune or Autoinflammatory?

No autoantibodies have been identified and linked to ankylosing spondylitis, thus meaning it is not generally considered an autoimmune disease. However, there are other characteristics that would be considered typical of an autoimmune disease.

For example, in “some mouse and rat models that resemble ankylosing spondylitis, the disease can be transferred from one animal to another by taking the lymphocytes [a type of white blood cell] from the diseased animal and injecting them into a healthy animal,” according to the Spondylitis Association of America.

This suggests a connection to the adaptive immune system, as T- and B-cells (the type of cells generated by the adaptive system) are lymphocytes.

The prevalence of an antigen subtype called HLA-B27 also points towards an autoimmune disease. Over 90% of people living with ankylosing spondylitis have HLA-B27, far more than the general population (the prevalence changes drastically depending on population and race, from 0.1%-0.5% of people of Japanese descent to 24% in northern Scandinavia).

As the above article mentions, it is theorized that HLA-B27 is able to activate a T-cell response, which would further link it to the immune system’s adaptive defense.

However, it is also believed that HLA-B27 may alter bacteria within the body and shape the response of the innate defense. This, combined with the lack of autoantibodies, would point towards an autoinflammatory disease.

A Bit of Both?

The innate and the adaptive arms of the immune system do not work entirely independently of one another. They combine in a sophisticated way in order to fight viruses, infections, bacteria, and other threats.

Similarly, it has been suggested that autoimmune diseases and autoinflammatory diseases are not entirely independent entities. Rather, it is possible there is a spectrum upon which different diseases fall. At each end, you may have diseases that can be considered purely one or the other, but it is possible that many immune-mediated inflammatory diseases share characteristics of both.

The way the HLA-B27 antigen has such a profound impact on the immune system as a whole means ankylosing spondylitis may well be a disease that falls somewhere in the middle.

It may seem like a small distinction to many people. For researchers, however, gaining a better understanding of the pathogenesis of such diseases is massively important in developing more effective treatment options.

The HLA-B family of antigens are a fascinating area of research, given the diverse effects they seem to have on the immune system. The greater an understanding we have of them, the more insight we gain into not only ankylosing spondylitis, but a whole range of immune-mediated inflammatory diseases.

Take a look at some of the other posts on the MyTherapy blog:

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