What is the most common disease associated with HLA-B27?

September 22, 2025 •

3 min read

With over 90% of individuals diagnosed carrying the gene, ankylosing spondylitis is the most common disease associated with HLA-B27. This discovery revolutionized the understanding of inflammatory arthritis and genetic predisposition in the early 1970s.

Quick Summary

Ankylosing spondylitis, a type of inflammatory arthritis that primarily affects the spine, is the most common and strongly linked disease associated with the HLA-B27 gene. While a significant majority of individuals with this condition have the gene, most people with HLA-B27 will never develop the disease.

Key Points

Ankylosing Spondylitis: This inflammatory arthritis is the most common disease associated with the HLA-B27 gene, affecting the spine and sacroiliac joints.
Genetic Risk vs. Diagnosis: A positive HLA-B27 test indicates an increased genetic risk for certain autoimmune conditions, but it does not guarantee a diagnosis.
Spondyloarthropathies: HLA-B27 is linked to a family of related diseases, including reactive arthritis, psoriatic arthritis, and acute anterior uveitis.
Diverse Triggers: Environmental factors, such as bacterial infections, can interact with the HLA-B27 gene to trigger reactive arthritis in susceptible individuals.
Comprehensive Evaluation: Diagnosis of these conditions requires a doctor to consider symptoms, medical history, physical exams, and imaging, in addition to genetic testing.
Treatment Focus: Management of HLA-B27-related diseases centers on reducing inflammation, controlling pain, and maintaining mobility through medication, exercise, and lifestyle changes.

Understanding the HLA-B27 Gene

Human Leukocyte Antigen B27 (HLA-B27) is a protein on the surface of white blood cells that assists the immune system in identifying pathogens. However, the presence of HLA-B27 is linked to an increased risk of autoimmune diseases where the immune system attacks healthy tissue. The exact reasons for this association are still being researched, with theories such as the 'arthritogenic peptide' and 'misfolding' being explored.

Ankylosing Spondylitis: The Primary Association

Ankylosing spondylitis (AS) is the most frequently associated condition with HLA-B27. This is a chronic inflammatory disease mainly impacting the spine and the sacroiliac (SI) joints. Inflammation can lead to fusion of vertebrae, known as ankylosis, which reduces flexibility and can cause a stooped posture in advanced cases, although current treatments can help prevent this. AS usually begins in late adolescence or early adulthood and is seen in both men and women, though historical understanding suggested a male predominance.

The Role of Genetics vs. Environmental Factors

It's important to understand that having the HLA-B27 gene doesn't automatically mean a person will develop AS. Although most people with AS have HLA-B27, only a small percentage of those with the gene actually get the disease. This indicates that other genetic factors and environmental triggers, like certain infections or gut microbes, likely contribute to the development of AS in individuals with the genetic predisposition.

Beyond Ankylosing Spondylitis: Other HLA-B27 Syndromes

Besides AS, HLA-B27 is connected to other inflammatory conditions collectively termed spondyloarthropathies. These include:

Reactive Arthritis: An arthritis triggered by an infection, often in the genitourinary or gastrointestinal tract.
Acute Anterior Uveitis (AAU): Inflammation of the front part of the eye, which can be the initial symptom of a spondyloarthropathy.
Psoriatic Arthritis: Arthritis in individuals with psoriasis, particularly affecting the spine.
Inflammatory Bowel Disease (IBD)-associated Arthritis: Arthritis linked to conditions like Crohn's disease and ulcerative colitis.

Diagnosis and Management of HLA-B27 Associated Conditions

Diagnosing conditions linked to HLA-B27 involves a thorough evaluation, including reviewing symptoms and medical history, a physical exam, and potentially blood tests for inflammation. While the HLA-B27 test is supportive, it's not used in isolation. Imaging like X-rays or MRI helps assess joint and spinal inflammation or damage.

Management aims to control inflammation and pain, maintain mobility, and slow disease progression. Treatment often includes a combination of:

Medication: NSAIDs are commonly used, and biologics may be prescribed for more severe cases.
Physical Therapy and Exercise: Essential for preserving spinal flexibility and posture.
Lifestyle Modifications: Managing weight and not smoking can help with symptoms.

Comparison of Key HLA-B27 Associated Diseases


Feature	Ankylosing Spondylitis (AS)	Reactive Arthritis	Acute Anterior Uveitis (AAU)
Primary Area Affected	Sacroiliac joints and spine	Joints (esp. lower extremities), urethra, eyes	Eye (iris and ciliary body)
Trigger	Genetic predisposition combined with environmental factors	Bacterial infection (e.g., Chlamydia, Salmonella, Yersinia)	Autoimmune response, highly linked to AS
Key Symptoms	Inflammatory back pain, morning stiffness, reduced spinal flexibility	Arthritis, urethritis (UTI-like symptoms), uveitis ('can't see, can't pee, can't climb a tree')	Unilateral eye pain, redness, sensitivity to light (photophobia)
Prevalence in HLA-B27+	High, over 90% of AS patients	60-85% of reactive arthritis patients	Approximately 50-60% of AAU patients

Conclusion: Understanding the Genetic Link

In summary, the HLA-B27 gene is strongly linked to several autoimmune conditions, with ankylosing spondylitis being the most common. The discovery of this genetic association has been vital in understanding disease susceptibility. However, a positive HLA-B27 test result is only one piece of the diagnostic process, which requires a full clinical assessment. Effective treatments are available to help manage these conditions. For more detailed information on HLA-B27 syndromes and their pathologies, consult authoritative medical resources like those available through the National Institutes of Health.

Frequently Asked Questions

HLA-B27 is a human leukocyte antigen, which is a protein on the surface of white blood cells. It helps the immune system identify foreign substances, but its presence is strongly linked to certain autoimmune diseases, including ankylosing spondylitis.

No, absolutely not. While a vast majority of people with ankylosing spondylitis carry the HLA-B27 gene, only a small percentage of people who have the gene ever develop the disease. It is a risk factor, not a diagnostic confirmation.

Common symptoms include chronic back pain and stiffness in the lower back and hips, especially noticeable in the morning or after periods of inactivity. Neck pain, fatigue, and eye inflammation (uveitis) are also possible.

Yes, some people with ankylosing spondylitis do not have the HLA-B27 gene. However, the disease may be less frequent or have different characteristics in those who are HLA-B27 negative.

Yes, HLA-B27 is strongly associated with acute anterior uveitis, an inflammation of the eye's iris and ciliary body. This can cause pain, redness, and sensitivity to light.

Reactive arthritis is a form of inflammatory arthritis that develops following an infection, typically in the gut or urinary tract. A high percentage of reactive arthritis patients, particularly those with a specific infection trigger, are HLA-B27 positive.

There is currently no cure for ankylosing spondylitis and other HLA-B27 associated diseases. However, a range of effective treatments, including medication, physical therapy, and exercise, can help manage symptoms and slow disease progression.