**Core Concept**
Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the axial skeleton, particularly the spine, and is characterized by a complex interplay between genetic predisposition, immune system dysregulation, and environmental factors.

**Why the Correct Answer is Right**
The correct answer is associated with the pathogenesis of AS. The disease is linked to the presence of HLA-B27 antigen, which is a major histocompatibility complex (MHC) class I molecule. HLA-B27 is believed to play a crucial role in the immune system's recognition of self-antigens, leading to an abnormal immune response and subsequent inflammation in the joints. The HLA-B27 antigen is present in approximately 90% of patients with AS, making it a strong genetic association.

**Why Each Wrong Option is Incorrect**
**Option A:** While HLA-B27 is a well-established genetic risk factor, it is not the only factor contributing to the development of AS. Other genetic and environmental factors also play a role.
**Option B:** HLA-A26 is not associated with AS; it is a different MHC class I molecule with no known link to the disease.
**Option C:** HLA-DR4 is associated with rheumatoid arthritis, not AS. It is a different MHC class II molecule that plays a role in the immune response, but it is not linked to AS.

**Clinical Pearl / High-Yield Fact**
It is essential to remember that the presence of HLA-B27 is not diagnostic for AS, as many individuals without the disease also carry this antigen. A thorough clinical evaluation, including radiographic and laboratory tests, is necessary to confirm the diagnosis.

**Correct Answer:** D. HLA-B27.