What Autoimmune Diseases Are Associated with HLA-B27?

The human leukocyte antigen B27 (HLA-B27) is a specific protein found on the surface of white blood cells that is strongly linked to a group of autoimmune and inflammatory diseases, primarily affecting the spine and other joints. The presence of HLA-B27 is a significant genetic marker for these conditions, though not everyone with the gene will develop them.

Key Autoimmune Diseases Associated with HLA-B27

Individuals positive for HLA-B27 are at an increased risk for developing a range of autoimmune conditions collectively known as spondyloarthropathies. These conditions often share similar features, including inflammation of the spine (spondylitis) and peripheral joints (arthritis), as well as inflammation of entheses (where tendons and ligaments attach to bone).

The primary autoimmune diseases and conditions associated with HLA-B27 include:

Ankylosing Spondylitis (AS)

Ankylosing spondylitis is the most classic and strongly associated condition with HLA-B27. It is a chronic inflammatory disease primarily affecting the spine, leading to severe pain and stiffness. Over time, inflammation can lead to the fusion of vertebrae, resulting in a rigid spine. Other joints, such as the hips and shoulders, can also be affected.

• Symptoms: Chronic back pain, particularly morning stiffness that improves with exercise, reduced flexibility of the spine.
• Impact: Can severely limit movement and lead to significant disability if untreated.
• Source: Mayo Clinic - Ankylosing Spondylitis

Reactive Arthritis (ReA)

Formerly known as Reiter's syndrome, reactive arthritis is a type of arthritis that develops in response to an infection in another part of the body, most commonly the gastrointestinal or genitourinary tracts. It is characterized by a classic triad of symptoms: arthritis, urethritis (inflammation of the urethra), and conjunctivitis (inflammation of the eye).

• Symptoms: Joint pain and swelling (often in knees, ankles, feet), eye inflammation (redness, irritation), and urinary problems.
• Trigger: Bacterial infections like Chlamydia trachomatis or certain food-borne bacteria (e.g., Salmonella, Shigella).
• Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) - Reactive Arthritis

Psoriatic Arthritis (PsA)

Psoriatic arthritis is a form of arthritis that affects some people with psoriasis, a skin condition characterized by red patches of skin covered with silvery scales. PsA can affect any joint in the body, and its severity can vary widely. When psoriatic arthritis affects the spine, it is strongly associated with HLA-B27.

• Symptoms: Joint pain, stiffness, and swelling; sausage-like swelling of fingers or toes (dactylitis); nail changes; and inflammation in the spine.
• Variability: Can range from mild to severe, affecting peripheral joints, spine, or both.
• Source: National Psoriasis Foundation - Psoriatic Arthritis

Enteropathic Arthritis (EA)

Enteropathic arthritis is a chronic inflammatory arthritis associated with inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis. This form of arthritis can affect both the spine (axial involvement) and peripheral joints. The axial form of enteropathic arthritis is more commonly linked to HLA-B27.

• Symptoms: Joint pain and inflammation, particularly in the lower back and large joints; often coincides with flare-ups of the underlying bowel disease.
• Associated Conditions: Crohn's disease and ulcerative colitis.
• Source: Crohn's & Colitis Foundation - Arthritis

Acute Anterior Uveitis (AAU)

Acute anterior uveitis is an inflammatory condition affecting the front part of the eye, specifically the iris and ciliary body. While it can occur as an isolated condition, it is a common extra-articular (outside the joint) manifestation of the spondyloarthropathies, particularly ankylosing spondylitis and reactive arthritis. A significant percentage of individuals with AAU are positive for HLA-B27.

• Symptoms: Eye pain, redness, light sensitivity (photophobia), and blurred vision, usually affecting one eye at a time.
• Recurrence: Can recur frequently and, if left untreated, may lead to vision loss.
• Source: American Academy of Ophthalmology - Uveitis

Understanding "B27 Disease"

Beyond these well-established conditions, a specific autoimmune condition known as "B27 disease" has been identified. This condition is characterized as a new autoimmune disease that affects millions worldwide. It is observed in individuals who are positive for HLA-B27 and also have ankylosing spondylitis (AS) or pre-ankylosing spondylitis and/or uveitis. This highlights a collective autoimmune state often seen in HLA-B27 positive individuals experiencing these specific inflammatory manifestations.

The Role of HLA-B27 in Autoimmunity

The exact mechanism by which HLA-B27 contributes to these autoimmune diseases is not fully understood, but several theories exist:

• Antigen Presentation: HLA-B27 is a major histocompatibility complex (MHC) class I molecule, meaning its primary function is to present peptides (fragments of proteins) to T-cells of the immune system. A defect in this presentation might lead to the immune system mistakenly attacking the body's own tissues.
• Molecular Mimicry: Some bacterial or viral peptides might resemble self-peptides presented by HLA-B27, triggering an autoimmune response following an infection.
• Misfolding: The HLA-B27 protein may misfold, leading to an endoplasmic reticulum stress response that triggers inflammation and immune activation.

Diagnosis and Management Considerations

Diagnosis of these HLA-B27 associated diseases typically involves a combination of:

• Clinical Evaluation: Assessment of symptoms, medical history, and physical examination.
• Imaging Studies: X-rays, MRI, or ultrasound to detect inflammation or damage in joints and soft tissues.
• Blood Tests: Including the HLA-B27 gene test, as well as inflammatory markers like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

Management generally focuses on reducing inflammation, relieving pain, and preventing disease progression. This can involve:

• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Disease-modifying antirheumatic drugs (DMARDs)
• Biologic therapies (e.g., TNF inhibitors)
• Physical therapy and exercise

Overview of HLA-B27 Associated Diseases