What Causes Ankylosing Spondylitis?

If you’ve been told you have ankylosing spondylitis (AS), you might have had two thoughts in rapid succession:
“Wait… how do I pronounce that?” followed very quickly by, “Why did this happen to me?”
While we still don’t have a single simple answer, researchers do know a lot more about what causes ankylosing spondylitis than they did even a decade ago.

The short version: ankylosing spondylitis is an autoimmune, inflammatory form of arthritis that mainly targets the spine and sacroiliac joints
(where the spine meets the pelvis). It seems to arise from a mix of genetic changes, immune system overreaction, and environmental triggers
such as infections and lifestyle factors. Not everyone with “risky” genes gets AS, and not everyone with AS has the same genetic markers,
which is why your doctor may say, “We don’t know exactly what caused it, but we know what’s going on.”

What Is Ankylosing Spondylitis, Exactly?

Ankylosing spondylitis is part of a family of conditions called axial spondyloarthritis. “Axial” refers to the spine and pelvis,
which explains why the main symptoms are inflammatory low back pain, stiffness, and trouble moving your spine the way you used to.
Over time, chronic inflammation can lead to new bone formation and, in some people, fusion (ankylosis) of the vertebrae.

AS is considered an autoimmune or immune-mediated disease. That means the immune system, which is supposed to attack invaders like viruses and bacteria,
mistakenly attacks healthy tissues insteadespecially the entheses (the spots where tendons and ligaments attach to bone).
In AS, those attachment points around the spine, pelvis, and sometimes hips and shoulders become inflamed, causing pain and stiffness that
usually feels worse after rest and better with movement.

So… What Actually Causes Ankylosing Spondylitis?

Here’s the honest answer: experts don’t know one single root cause. Instead, they see ankylosing spondylitis as the result of
several factors teaming up:

• Genetics: certain genes, especially HLA-B27, strongly increase your risk.
• Immune system misfires: your immune system reacts in a way that promotes chronic inflammation in the spine and pelvis.
• Environmental triggers: factors like infections, gut bacteria changes, and lifestyle habits may “flip the switch” in people who are genetically predisposed.

An Autoimmune Misfire in the Spine

In AS, immune cells seem to mistake normal structures in the spine and sacroiliac joints for dangerous intruders.
They release inflammatory chemicals (cytokines) that keep the area irritated and swollen.
This inflammation can cause pain and stiffness in the short term and, if it continues, can eventually lead to bone changes and fusion.

Think of it as a smoke alarm that keeps going off even though there’s no fireor the “fire” is long gone.
The alarm (your immune system) gets stuck in the “on” position in very specific areas of the body.

Chronic Inflammation and New Bone Formation

One of the most distinctive, and frustrating, features of ankylosing spondylitis is the way your body tries to “repair” that ongoing inflammation.
The spine may respond by forming new bone along ligaments and between vertebrae.
Over time, these bony bridges can fuse parts of the spine together, leading to reduced flexibility and that classic “bent-forward” posture in severe cases.

The Star of the Show: The HLA-B27 Gene

When people talk about what causes ankylosing spondylitis, one name comes up again and again: HLA-B27.
This is a specific version (variant) of a gene called HLA-B that helps your immune system tell the difference between your own cells and foreign invaders.
In many people with AS, HLA-B27 shows up as a sort of genetic calling card.

Large studies have found that:

• Most people with ankylosing spondylitis carry the HLA-B27 gene, especially in certain ethnic groups.
• Among white populations with AS, up to 85–95% may be HLA-B27 positive.
• But only a small percentage of people who have HLA-B27 actually develop ankylosing spondylitis.

That last point is crucial: HLA-B27 increases risk, but it’s not destiny.
It’s like having a loaded paintball gun in the closet. The gene loads the gun, but something has to pull the trigger.

How Might HLA-B27 Contribute to AS?

Researchers have several theories:

• Mistaken identity: HLA-B27 may present “self” proteins to the immune system in a way that makes them look foreign,
  encouraging the immune system to attack your own tissues.
• Misfolded proteins: HLA-B27 protein might misfold inside cells, creating stress that triggers inflammation.
• Microbiome interaction: HLA-B27 may influence which gut bacteria thrive in your body, shaping immune responses in ways that contribute to AS.

None of these theories fully explain every case of ankylosing spondylitis, but together they give a big-picture view:
HLA-B27 seems to make the immune system more likely to overreact in certain ways.

Can You Have AS Without HLA-B27?

Yes. Many people with AS do not have HLA-B27, especially outside of European ancestry groups.
In some populations, other HLA types or additional genes appear to play a larger role.
That’s why a negative HLA-B27 test does not completely rule out ankylosing spondylitis.

Other Genes Joining the Party

HLA-B27 gets the headlines, but it’s far from the only genetic player.
Genome-wide association studies have identified dozens of other genes and regions involved in immune regulation and inflammation that may contribute to AS risk.

Some of these genes are involved in:

• Regulating immune signaling molecules like interleukin-17 (IL-17) and tumor necrosis factor (TNF).
• Maintaining barriers in the gut and other tissues.
• Controlling how immune cells develop and respond to threats.

You can think of ankylosing spondylitis as a “polygenic” condition:
it’s not one gene flipping a single switch, but many genes nudging your immune system in a more inflammatory direction.
The more of these risk variants you have, the higher your chance of developing ASespecially if life events and environmental factors push in the same direction.

Environmental Triggers: When Genes Meet Real Life

If genes are the loaded paintball gun, environmental triggers are the finger on the trigger.
Researchers still don’t have a complete list of these triggers, but several suspects keep coming up:

Infections and the Gut Microbiome

Many experts believe that certain infections or shifts in the gut microbiome (the community of bacteria in your intestines) may spark ankylosing spondylitis in genetically susceptible people.

• Gut inflammation: People with AS often have signs of inflammation in the intestines,
  even if they don’t have obvious digestive symptoms. This suggests that the gut is part of the story.
• Bacteria “cross-talk”: Some bacteria might trigger immune responses that inadvertently target joints and entheses
  (a concept called molecular mimicry, where bacterial proteins resemble the body’s own proteins).

The details are still under active study, but it’s increasingly clear that what happens in the gut does not stay in the gut
especially for conditions like ankylosing spondylitis.

Smoking and Other Lifestyle Factors

Lifestyle habits don’t “cause” AS by themselves, but they can influence risk and severity:

• Smoking: Smoking is linked to a higher likelihood of developing AS in at-risk individuals
  and to more severe disease, including more spinal damage on imaging.
• Obesity and physical inactivity: These can worsen overall inflammation and make back pain and stiffness harder to manage,
  even if they aren’t the original cause.
• Stress and sleep disruption: These don’t directly cause AS, but they can amplify pain
  and make it more difficult for the body to manage inflammation.

Think of these factors as volume knobs. They may not turn AS “on,” but they can turn it upor help turn it downwith good management and support.

Who Is Most at Risk for Ankylosing Spondylitis?

While ankylosing spondylitis can affect almost anyone, certain patterns stand out in large studies:

• Family history: Having a close relative with AS or related conditions significantly raises your risk.
• HLA-B27 positivity: Carrying this gene increases risk, especially if you also have a family history.
• Age: Symptoms usually start in the teens or 20s and rarely begin after age 45.
• Sex: AS has historically been diagnosed more often in men, though improved imaging and awareness show that women are affected more than once thought.
• Ethnicity: HLA-B27 is more common in some populations than others, which influences how often AS appears in those groups.

Remember: risk is about probability, not certainty. You can have multiple risk factors and never develop ASor have AS with only one obvious risk factor.

What Does NOT Cause Ankylosing Spondylitis?

With any chronic condition, it’s easy to blame yourself or your past choices.
So let’s clear up a few myths about what does not cause ankylosing spondylitis:

• Bad posture: Slouching may give you sore muscles, but it doesn’t cause AS.
• Heavy lifting or a single injury: Injuries can trigger short-term pain or even long-term back problems, but they don’t cause this autoimmune disease.
• Stress alone: Stress can make symptoms feel worse, but it’s not the root cause of AS.
• “Sleeping wrong” or the wrong mattress: These can certainly add discomfort, but they don’t create autoimmune spinal arthritis.

In other words, if you’ve been mentally replaying every backpack you carried or mattress you bought:
you can give yourself a break. Ankylosing spondylitis is not your fault.

Can You Prevent Ankylosing Spondylitis?

Because we can’t change our genes (at least not yet) and we don’t fully understand all the triggers,
there’s no guaranteed way to prevent ankylosing spondylitis.

That said, there are steps that may help lower your overall inflammation and protect long-term health:

• Not smoking or getting help to quit if you do smoke.
• Staying physically active with exercises that support flexibility and core strength.
• Prioritizing good sleep, stress management, and a balanced, nutrient-rich diet.
• Seeking evaluation early if you have persistent inflammatory back pain, especially with a family history of AS.

Early diagnosis and treatment can’t change your underlying genetics, but they can make a big difference
in how ankylosing spondylitis affects your daily life and long-term mobility.

When to Talk With a Healthcare Professional

It’s a good idea to talk with a healthcare professionalideally a rheumatologistif you notice:

• Low back pain and stiffness lasting more than three months.
• Pain that’s worse in the morning or at night and improves with movement, not rest.
• Alternating buttock pain, which can reflect sacroiliac joint involvement.
• Unexplained fatigue, eye redness and pain, or other inflammatory symptoms.

A rheumatologist can review your symptoms, medical and family history, physical exam, imaging tests,
and blood work (including HLA-B27) to determine whether ankylosing spondylitis or another condition might be the cause.
This article is for education and general information only and is not a substitute for professional medical advice, diagnosis, or treatment.

Real-Life Experiences: Living With the Question “What Caused My AS?”

Beyond all the genetics, biomarkers, and research papers, ankylosing spondylitis is something real people live with every day.
And nearly everyone who hears the diagnosis eventually asks the same question: “Why me?”

For some, the story starts with a parent or grandparent who had “a bad back” long before AS was widely recognized.
Maybe your dad walked with a slight forward bend, or your aunt could never quite straighten her neck.
When your own back began to hurt in your 20s, it was easy to chalk it up to long hours at a desk or a new workout routine.
Only later did the pattern come into focus: family history plus persistent inflammatory back pain plus a positive HLA-B27 test.

Others have no known family history at all. One person might remember a nasty stomach bug or infection that seemed to set off months of fatigue and back pain.
Another might trace things back to a high-stress periodgraduating from college, starting a new job, caring for a babywhen sleep was scarce
and their immune system seemed to be constantly “on.” While we can’t say these life events caused ankylosing spondylitis, they often become emotional markers
people use to make sense of how and when their symptoms first appeared.

Many people describe years of being told their pain was from muscle strain, poor posture, or simply “getting older,” even when they were in their 20s or 30s.
One person might recall being given a new mattress; another was prescribed round after round of basic pain relievers with no real explanation.
When they finally reach a rheumatologist who orders the right imaging and lab tests, the diagnosis of AS can feel like both a shock and a strange kind of relief.

Emotionally, the lack of a single, clear cause can be tough. It’s natural to search your memory for something you did “wrong”:
Did I sit too much? Did that lifting job in college damage my spine? Should I have exercised more?
Over time, most people find it helpful to shift the focus away from blame and toward understanding risk factors and managing what they can influence today:
things like staying active, not smoking, following treatment plans, and building a supportive care team.

Support groups and online communities can be powerful here.
When someone else says, “My doctor also told me they’re not exactly sure what caused it, but my genetics and immune system probably teamed up,”
it can be surprisingly comforting. You realize you’re not the only one living with that unanswered “why.”

Some people come to see their story as a mix of luck, biology, and timing:
“I drew the short straw with certain genes, and then something in my life and immune system flipped the switch.”
That framing doesn’t magically fix pain or stiffness, but it can help turn down the volume on guilt.
You didn’t cause ankylosing spondylitis by sleeping wrong, working hard, or being stressed out.

As research advances, we may get better at pinpointing the exact pathways that lead from genetic risk to full-blown AS.
For now, many people find peace in focusing on the part of the story they can actively shape:
learning about their condition, partnering with knowledgeable clinicians, staying as strong and flexible as possible,
and giving themselves credit for living life fullyeven with a spine that occasionally protests every time they bend to tie their shoes.

The Bottom Line

Ankylosing spondylitis doesn’t have a single, simple cause.
Instead, it arises from a combination of genetic susceptibility (especially HLA-B27 and other immune-related genes),
immune system misfires, and environmental influences such as infections, gut microbiome changes, and lifestyle factors.

You can’t control your genes, and you likely didn’t do anything to “cause” your ankylosing spondylitis.
What you can do is work with your healthcare team to understand your specific risk factors,
manage inflammation, protect your spine, and build daily habits that support your long-term health and mobility.
Knowledge about what causes AS isn’t just interesting backgroundit can be a powerful tool for self-compassion and smart, proactive care.