Ankylosing spondylitis (AS) is a chronic inflammatory condition that primarily affects the spine, leading to pain, stiffness, and potentially a loss of spinal flexibility over time. While commonly associated with the Human Leukocyte Antigen B27 (HLA-B27) genetic marker, a notable percentage of patients with AS do not carry this gene. This article discusses AS, its connection to HLA-B27, and how the condition is understood and managed in HLA-B27 negative individuals.
Understanding Ankylosing Spondylitis and HLA-B27
Ankylosing spondylitis is a form of arthritis characterized by inflammation of the vertebrae in the spine and the sacroiliac joints, which connect the base of the spine to the pelvis. Over time, this inflammation can cause new bone formation, potentially leading to sections of the spine fusing together, resulting in a hunched posture and reduced flexibility. The condition can also affect other areas, such as the hips, shoulders, and peripheral joints, and may involve extra-articular manifestations like uveitis (eye inflammation), psoriasis, and inflammatory bowel disease.
The HLA-B27 gene is a protein found on the surface of white blood cells and plays a role in the immune system’s ability to distinguish between the body’s own cells and foreign invaders. While HLA-B27 is present in 80% to 90% of AS patients in certain populations, it is a genetic marker and not a direct cause of the disease. Many individuals who carry the HLA-B27 gene never develop AS; only about 5-10% of those with a positive test will develop AS.
The Reality of HLA-B27 Negative Ankylosing Spondylitis
While HLA-B27 is a significant risk factor for AS, a considerable percentage of individuals with the condition test negative for this gene. In Caucasian patients, approximately 10% of those with AS may be HLA-B27 negative, while in Black Americans, this figure can be as high as 37%. This indicates that AS can develop in the absence of the HLA-B27 marker, suggesting other genetic and environmental factors are involved.
Other genetic variations, beyond HLA-B27, have been identified that influence the risk of developing AS. HLA-B27 negative AS cases may exhibit subtle differences in disease presentation. Patients without the HLA-B27 gene often experience a higher frequency of peripheral arthritis, dactylitis (inflammation of a whole digit), and extra-articular manifestations like psoriasis and inflammatory bowel disease. Some studies suggest HLA-B27 negative patients may have a later age of symptom onset and diagnosis compared to those who are HLA-B27 positive.
Diagnosing Ankylosing Spondylitis Without the HLA-B27 Marker
Diagnosing AS in the absence of the HLA-B27 marker relies on a comprehensive clinical assessment, including evaluating symptoms, performing a physical examination, and utilizing imaging studies. Inflammatory back pain is a hallmark symptom, typically characterized by an insidious onset, pain lasting more than three months, improvement with exercise but not rest, and being worse at night or in the early morning. Patients may also experience morning stiffness and reduced spinal mobility.
Imaging plays an important role in diagnosis, especially Magnetic Resonance Imaging (MRI) of the sacroiliac (SI) joints. MRI is highly sensitive in detecting early inflammatory changes, such as bone marrow edema, even before structural damage is visible on traditional X-rays. While X-rays can show definitive sacroiliitis in later stages, MRI can reveal non-radiographic axial spondyloarthritis, a form of the disease where symptoms are present but X-ray changes are not yet evident. Other laboratory tests, such as elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), may indicate inflammation but are not sufficient for diagnosis alone, as these markers can be normal in up to 50% of AS patients and can be elevated due to various other conditions.
Managing HLA-B27 Negative Ankylosing Spondylitis
Treatment strategies for HLA-B27 negative AS generally mirror those for HLA-B27 positive cases, focusing on reducing pain, stiffness, and inflammation, preventing disease progression, and maintaining mobility. Non-steroidal anti-inflammatory drugs (NSAIDs) are often the first-line medication, helping to alleviate pain and reduce inflammation. Regular physical therapy and a consistent exercise regimen are also important, as they help maintain spinal mobility, improve posture, and manage pain.
For individuals with more severe or persistent symptoms not responding sufficiently to NSAIDs and physical therapy, biologic medications may be considered. These advanced therapies target specific inflammatory pathways in the immune system, which can significantly improve symptoms and slow disease progression. While there is no cure for AS, a multidisciplinary approach involving medication, exercise, and lifestyle adjustments can help individuals with HLA-B27 negative AS manage their condition and maintain a good quality of life.