Wait, spondylitis isn’t autoimmune?

Until recently, I felt confident telling people I have an autoimmune disease. After all, any inflammatory arthritis is clearly autoimmune, right? My body is attacking itself and causing inflammation, so it must be autoimmune.

Wrong. I was surprised to learn about a new category of conditions that has been identified: autoinflammatory. Knowing whether spondyloarthritis is autoimmune or autoinflammatory will be important for finding new treatments. But what does autoinflammatory mean?

Immunity overview

The immune system has two parts: innate immunity and adaptive immunity. Innate immunity isn’t specific to any one threat that your body might face. The innate immune system includes barriers like skin and mucus as well as cells that attack foreign substances in the body and cause inflammation. These defenses aren’t specific to one type of bodily threat, and the cells attack anything that gives off the right chemical signals.

Adaptive immunity is built up against a single specific threat. Once the immune system identifies something that shouldn’t be there, it produces antibodies, cells specifically made to attack that invader. The immune cells then “remember” that disease causer, or pathogen, so that if it returns in the future, it can be gotten rid of before it makes you sick again. This is why you shouldn’t get the same disease twice. Vaccines work to “train” the immune system without actually making you sick.

The response time of the adaptive immune system is much slower than the innate immune system, which is always ready to attack. However, the adaptive immune system is much more effective at ridding the body of pathogens.

Autoimmunity and autoinflammation

It’s the adaptive immune system that’s involved in autoimmune diseases. The immune system mistakenly produces antibodies, called autoantibodies, against parts of the body. As a result, the immune system attacks the body like it’s a foreign invader. For example, rheumatoid factor, an autoantibody, is found in the blood of people with rheumatoid arthritis. The body has mistakenly “learned” to attack components in joints. Men and women have differences in their immune system function due to their different hormones, which is believed to be the reason why more women get autoimmune diseases.

Autoinflammatory conditions can’t be tied to any autoantibody. In autoinflammation, the innate immune system becomes confused and causes inflammation without threats being present. While a specific body system might be mainly affected, like the GI tract in Crohn’s disease, the nonspecific nature of the innate immune system means that other systems are inevitably affected as well. A number of autoinflammatory conditions have been tied to specific genes that cause defects in the immune system, but not all autoinflammatory diseases work like this. For example, familial Mediterranean fever is associated with a single gene but Crohn’s disease is not. Autoinflammatory conditions are equally common among men and women.

Is spondylitis autoimmune or autoinflammatory?

Spondyloarthritis stumps researchers because it’s something of a mix between autoimmune and autoinflammatory. There are a lot of arguments for classifying it as autoinflammatory: there is no detectable autoantibody, the gender ratio is equal, and it responds to drugs used for autoinflammatory diseases. Genetics play an important role in development of spondyloarthritis, more than in typical autoimmune diseases. In addition, factors like physical trauma and infections are more tied to development of spondyloarthritis than to an autoimmune disease like rheumatoid arthritis.

However, studies in mice have shown that transferring immune cells from a mouse with spondylitis to one without gives the second mouse spondylitis, which should only happen with autoimmune diseases. Because of these differing features, many doctors agree that spondyloarthritis is a “mixed pattern disease,” meaning it has characteristics of both autoimmune and autoinflammatory disease and can’t correctly be classified as either.

That means that, at this point, there’s no one word you can use to describe spondylitis that’s “right.” In addition to having a scary-sounding name, there’s no easy way to explain it. It’s kind of autoimmune, but not really, and kind of autoinflammatory, but not really.

Perhaps with future research, we’ll know better what causes patterns of autoimmune and autoinflammatory disease, and we’ll be able to describe spondylitis better.

-Bri

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