The Human Leukocyte Antigen (HLA) system is a complex family of genes located on chromosome 6, part of the Major Histocompatibility Complex (MHC). This system plays a role in the body’s immune surveillance. HLA genes provide instructions for making proteins that sit on the surface of most cells, including white blood cells.
These surface proteins act like identification tags, allowing the immune system to distinguish between the body’s own healthy cells and foreign invaders. HLA-B27 is one specific protein marker strongly associated with an increased risk for inflammatory conditions. Its presence is a significant genetic susceptibility factor, not a direct cause of disease.
The Genetic Mechanism of HLA-B27 Transmission
The inheritance of the HLA-B27 gene follows the principles of Mendelian genetics, similar to other genes passed down from parents to children. The entire cluster of HLA genes is inherited as a unit, referred to as a haplotype. Each person receives one HLA haplotype from their mother and one from their father.
Because the HLA-B27 gene is part of this haplotype unit, it is transmitted co-dominantly. If one parent carries the gene, their child has a fifty percent chance of inheriting that specific haplotype, irrespective of the child’s sex.
If a child inherits the HLA-B27 gene, they carry it throughout their life. The presence of the gene is not altered by environmental factors or disease development. While the likelihood of inheriting the gene increases if both parents are carriers, the 50% chance applies when only one parent is positive.
The gene itself is one of the most polymorphic in the human genome, with over 200 known subtypes or alleles. While the majority of these subtypes are associated with disease risk, a few rare variants, such as HLA-B27:06 and HLA-B27:09, are considered non-disease associated. The inheritance of the specific allele determines the potential risk profile.
Carrying the Gene Versus Developing Symptoms
A crucial distinction in understanding HLA-B27 is that inheriting the gene does not mean a person will automatically develop an associated inflammatory condition. This phenomenon is known as incomplete penetrance. The gene acts as a significant risk factor, but it is not a direct cause of disease on its own.
In the general United States population, the prevalence of the HLA-B27 gene is estimated to be around six to eight percent. However, only a small fraction of these carriers will ever develop a related condition, such as Ankylosing Spondylitis (AS). Estimates suggest that only about five to ten percent of people who are positive for HLA-B27 will develop AS.
The development of symptoms requires the presence of other genetic and environmental factors. Environmental triggers can include specific infections, such as those caused by certain bacteria, which may launch the autoimmune process. The state of the gut microbiome is also theorized to play a role.
Other non-HLA genes contribute to the overall risk of developing these inflammatory diseases. Therefore, HLA-B27 is viewed as a necessary but insufficient component for disease onset, establishing a genetic susceptibility modified by other factors.
Diseases Linked to the Presence of HLA-B27
The HLA-B27 gene is most strongly associated with a group of inflammatory, autoimmune conditions collectively termed the spondyloarthropathies. These disorders are characterized by inflammation, often affecting the spine, peripheral joints, and the sites where tendons and ligaments attach to bone.
The condition with the strongest link to the HLA-B27 allele is Ankylosing Spondylitis (AS), a chronic disease primarily affecting the spine and sacroiliac joints. Approximately eighty to ninety percent of individuals diagnosed with AS are found to be positive for HLA-B27. The gene’s presence is often used as a supportive diagnostic marker when symptoms are consistent with the disorder.
Other conditions in the spondyloarthropathy spectrum are also associated with the HLA-B27 marker, though the strength of the link varies. Reactive Arthritis, which often follows an infection, shows a high association (sixty to ninety percent of affected patients carry the gene). Psoriatic Arthritis is linked in a lower but significant percentage of cases.
The HLA-B27 allele is also strongly linked to acute anterior uveitis (AAU), an inflammatory condition of the eye. About fifty percent of patients with AAU are HLA-B27 positive.