In clinical practice, I often see patients with HLA-B27 positive labs asking the doctor, “Do I have ankylosing spondylitis?” . Some patients may think that if their blood tests are negative for HLA-B27, they do not have ankylosing spondylitis. Some patients with ankylosing spondylitis may hope that their HLA-B27 will turn out to be negative. So is a positive HLA-B27 a sign of ankylosing spondylitis? Does this indicator turn negative? First, let’s understand what HLA-B27 is. HLA is a 4-megabase region on human chromosome 6 that includes class I, II, and III genes. HLA-B27 belongs to HLA class I genes, which are found on the surface of all nucleated cells. Individuals with certain specific HLA alleles are predisposed to a particular disease, a typical example being ankylosing spondylitis. The rate of HLA-B27 antigen positivity in the patient population is as high as 58% to 97%, while in the healthy population it is only 1% to 8%. The risk rate (RR) for ankylosing spondylitis in HLA-B positive individuals is calculated to be 55-376 times greater than that in negative individuals. Second, is a positive HLA-B27 a diagnosis of ankylosing spondylitis? Although HLA-B27 and ankylosing spondylitis are closely related, ankylosing spondylitis is a polygenic disease and has been correlated with environmental and other factors. In fact, studies have found that although the majority of people with ankylosing spondylitis are HLA-B27 positive, the percentage of people with HLA-B27 positive disease is only a small percentage. Therefore, the diagnosis of ankylosing spondylitis also requires a combination of clinical manifestations, joint mobility, and imaging, not just a positive blood HLA-B27 that means having the disease. By the same token, ankylosing spondylitis can also be diagnosed in patients who are HLA-B27-negative with typical clinical and imaging findings. Therefore HLA-B27 is only a reference when we diagnose ankylosing spondylitis. Finally, is it possible to turn negative for HLA-B27, and is the disease cured if it turns negative? In clinical practice, patients with ankylosing spondylitis often request repeated tests for HLA-B27 in the hope that it will turn negative. Some patients wonder why I am still positive for HLA-B27 even though my symptoms have improved and I have almost no joint pain after treatment. In fact, as mentioned earlier in this article, HLA-B27 is genetically determined by the human body, which is determined at birth and cannot be changed. Therefore, there is no necessary connection between HLA-B27 and the effectiveness of disease treatment. Some patients say that some small clinics where doctors promise not only to treat the disease but also to turn HLA-B27 negative are against common scientific knowledge, and that visits to such clinics often delay the disease. Ankylosing spondylitis, an ancient disease, has been around for more than two thousand years. In the last two hundred years, the understanding of this disease has advanced by leaps and bounds. With the development of medicine, ankylosing spondylitis is now a detectable and treatable disease, but diagnosis and treatment of ankylosing spondylitis also depends on specialized doctors and specialized departments.