When doctors encounter patients with chronic low back pain, they will sometimes recommend HLA-B27 testing after some consultation. There are various explanations on the internet that seem to be more and more unclear. It is not uncommon to see a patient with a test report looking for advice from a doctor who explains that a positive HLA-B27 cannot be said to be ankylosing spondylitis, and that a negative HLA-B27 test cannot rule out ankylosing spondylitis. When a patient friend hears this, they are suspicious – wouldn’t that be a waste of time? Some of them will be quite direct and say, “I can’t be sure what the disease is, it’s a waste of money! But is it really meaningless to check for HLA-B27 and is it a waste of money? And listen to me. 1, to know what is HLA-B27 HLA-B27 is what? The HLA-B27 gene is a part of the genetic material DNA that is present in the nucleus of human cells. The HLA gene is an inherent part of the human body, and HLA can be divided into HLA-A, HLA-B, HLA-C, etc. There are more HLA-B such as HLA-B7, HLA-B8, HLA-B13, HLA-B18, and of course HLA-B27. HLA-B27 is like a human blood type, a person with type A blood will not become type B next time he or she checks, and HLA-B27 is not a painful condition. HLA-B27 is not positive when the pain is severe, but becomes negative when it is relieved. HLA-B27 is not a gene that everyone has, but once it is found to be positive, it means that the person has the gene and is unlikely to turn negative again. The HLA-B27 gene is transcribed, translated, and finally produces the HLA-B27 molecule that appears on the surface of the cell membrane. To detect HLA-B27, you can check both the HLA-B27 molecule and the HLA-B27 gene. The current method of checking HLA-B27 is mainly to check for HLA-B27 molecules, that is, to check for the presence of HLA-B27 protein molecules on the surface of cell membranes. Although each hospital may use different testing methods, either by micro lymphocytotoxic method or by flow cytometry, the accuracy of these tests is high. However, proteins are strange things, and the stability of proteins receives many influencing factors, and structural or environmental changes may affect the test results, so in rare cases, it may happen that what was originally HLA-B27 positive turns out to be a negative test. In this case, it can be determined by testing for the HLA-B27 gene. Because of the high stability of the gene, for example, the archaeological community can perform genetic testing on ancient animals or human cadavers, and the fact that the gene can be tested even after so long preservation shows how stable the gene is. Therefore, the results of strict genetic testing are the most certain. When we at the Zhongshan Hospital encounter conflicting test results, we sometimes perform genetic testing to determine them. If genetic testing is so accurate, why not just use genetic testing? For example, in the first step, DNA is extracted, and there are many steps to extract DNA alone; in the second step, gene amplification is performed, and then electrophoresis is performed. Electrophoresis requires gel preparation, and it takes about half an hour to wait for the hot gel to cool down and become solid. After the gel becomes solid, it takes another 10-20 minutes to run electrophoresis. After doing a set of down time, half a day is not less. Therefore, nowadays, unless it is necessary, HLA-B27 molecule is usually detected. 2, HLA-B27 why positive can not be sure that ankylosing spondylitis, and negative can not exclude ankylosing spondylitis? We know that the common ABO blood types are A, B, O, and AB. There are also many subtypes of the HLA-B27 gene. More than 130 HLA-B27 subtypes have been identified, ranging from HLA-B*27:01, HLA-B*27:02, HLA-B*27:03, …… to HLA-B27:135. Studies conducted by our group over the years in Chinese populations have shown that the most common HLA-B27 subtypes in Chinese Han Chinese are HLA-B27 subtype is HLA-B*27:04, followed by HLA-B*27:05; other subtypes detected in the Chinese population include HLA-B*27:02, HLA-B*27:06, and HLA-B*27:15. Some HLA-B27 subtypes are considered to be protective against ankylosing spondylitis, e.g. HLA-B*27:06, HLA-B*27:09. Some subtypes are positive in people with ankylosing spondylitis, e.g. HLA-B*27:15 is positive in people with the disease that we have found so far. Some of them are diseased and some of them are healthy. Through large-scale analysis, it has long been found that the rate of HLA-B27 positivity in ankylosing spondylitis is much higher than the rate of HLA-B27 positivity in the healthy population, so it is believed that HLA-B27 is closely related to ankylosing spondylitis. It is for this reason that ankylosing spondylitis is considered highly likely when HLA-B27 is found to be positive, but it cannot be used to confirm ankylosing spondylitis. Scientists have long found that in addition to the possible manifestation of ankylosing spondylitis in those who are HLA-B27 positive, a proportion of those who are HLA-B27 negative also develop ankylosing spondylitis. This empirically suggests that a negative test for HLA-B27 does not rule out ankylosing spondylitis. Several major international gene sequencing studies, including a 2011 study by our group in a Chinese population, have also found that in addition to HLA-B27, a number of other non-HLA genes are also strongly associated with ankylosing spondylitis. This also scientifically confirms that a negative HLA-B27 result cannot be used to rule out ankylosing spondylitis. 3. Since the HLA-B27 test does not confirm nor negate ankylosing spondylitis, what exactly is the use of checking it? Article 2 of the previous article mentions the reasons why it is neither certain nor negative for ankylosing spondylitis. So is there value in checking for HLA-B27? The value of testing for HLA-B27 is that, although it does not yield definitive results, it can yield valuable hints that those who are positive for HLA-B27 should be on high alert for a condition such as ankylosing spondylitis and need further history and examination to determine if it is ankylosing spondylitis. This more in-depth examination includes a variety of relevant imaging tests such as ultrasound, X-rays, CT, and even MRI. The areas examined include the spine, sacroiliac joints, hip joints, and tendon attachments. 4, HLA-B27 can neither confirm nor deny ankylosing spondylitis, so what is the basis for diagnosing ankylosing spondylitis? As the name implies, ankylosing spondylitis involves the joints of the spine and restricts movement. The current diagnosis of ankylosing spondylitis is still based on the 1966 New York criteria and the 1984 revised New York criteria. The first of these two criteria is the presence of clinical symptoms, such as low back pain, restricted lumbar spine movement, restricted thoracic movement, and low back pain that decreases with activity and does not improve with rest; the second is the presence of sacroiliac arthritis to meet the criteria. Inside the New York criteria and the revised New York criteria, there is no mention of HLA-B27, that is, regardless of HLA-B27 positive or negative, as long as the clinical manifestations of ankylosing spondylitis are achieved, there is the achievement of the corresponding sacroiliac arthritis criteria, it can be classified as ankylosing spondylitis. Therefore, after asking patients if they have the corresponding symptoms, rheumatologists will mostly suggest that they do a sacroiliac joint examination, because this examination is a very important condition for the diagnosis of ankylosing spondylitis. 5.Does HLA-B27 have any other role besides suggesting the possibility of ankylosing spondylitis? The HLA-B27 gene is closely related to ankylosing spondylitis and is also associated with uveitis. Some HLA-B27-positive patients develop uveitis, and some of them eventually develop ankylosing spondylitis. In patients with ankylosing spondylitis, there are some patients who initially develop manifestations that may also be ocular inflammation. Our studies have shown that patients with ankylosing spondylitis whose HLA-B27 subtype is the HLA-B*27:05 subtype have a higher chance of developing uveitis. In addition, it has also been shown that HLA-B27-positive ones are more severe than HLA-B27-negative patients. 6. Will ankylosing spondylitis occur in the future if I am currently asymptomatic but tested positive for HLA-B27? The answer to this question, as stated in #2 above, is: not necessarily. There are two reasons for this: 1) If further testing for HLA-B27 subtype reveals that it is HLA-B*27:06 or HLA-B*27:09 subtype, then the likelihood of future ankylosing spondylitis is small; if it is found to be HLA-B*27:15, then the likelihood of ankylosing spondylitis is perhaps more likely. Of course, the population size of our study is in a limited number of people, and if more HLA-B*27:15 subtypes are found in the future, we may be able to further expand the data and come up with more credible results. 2) We can’t look at the problem in a static way, everything is developing and changing, and just because it doesn’t happen today doesn’t mean it won’t happen in the future. Some HLA-B27 subtypes can be seen in both patients and healthy people, which also means that both possibilities exist. In my opinion, as long as the clinical manifestations of the disease do not occur, there is no need to worry too much. 7.What other diseases might HLA-B27 be positive for besides ankylosing spondylitis? Ankylosing spondylitis is one of a group of diseases typically included in spondyloarthritis, which includes ankylosing spondylitis, psoriatic arthritis, reactive arthritis (Wright’s syndrome), inflammatory bowel disease arthritis, juvenile spondyloarthropathy and undifferentiated spondyloarthropathy. Arthritis is divided into two main categories: medial spondyloarthritis and peripheral spondyloarthritis. Medial spondyloarthritis includes ankylosing spondylitis and also includes patients who have spinal joint involvement but do not yet meet the New York criteria for ankylosing spondylitis mentioned earlier. HLA-B27 positivity may occur in all of these groups of diseases. 8. Will the offspring be HLA-B27 positive if they are HLA-B27 positive? Genetically speaking, if one parent is tested positive for HLA-B27, it will definitely be passed on to the offspring (inevitability). However, inheritance is also probabilistic (chance), meaning that if 100 children are born, some of them may be HLA-B27 positive and some of them may be HLA-B27 negative.