Discovery of HLA and HLA-B27 HLA (human leukocyte antigen) is the expression product of human Major Histocompatibility Complex (MHC), which is classified into class I according to the structure, function and tissue distribution of HLA antigens, According to the different structure, function and tissue distribution of HLA antigens, they are classified into class I, class II and class III molecules, among which class I molecules include HLA-A, -B and -C series of antigens, which are widely distributed on the surface of nucleated cells in various tissues. The first HLA antigen was discovered by Jean Dausset in 1958, and until the 1970s, HLA gradually became an important research hotspot in the disciplines of immunogenetics and rheumatology, etc. In 1973, Brewerton et al. reported that there was a close correlation between HLA-B27 and ankylosing spondylitis (AS), and thus HLA-B27 became the first HLA antigen to be discovered. Thus, HLA-B27 became the first antigen found to be associated with an MHC molecule for a human disease. HLA-B27 molecular structure Detection of HLA and HLA-B27 The detection of HLA antigens has evolved from microcytotoxicity (one of the serologic methods), as initially proposed by Terasaki and McClelland, to cytotyping, DNA typing, and flow cytometry.11 At the 11th IHW in 1991, and at the subsequent WHO-HLA Nomenclature Committee, it was stated that all new HLA antigens that are not yet known to have been detected in the human population should have been identified by the IHW. The 11th IHW in 1991 and the subsequent WHO-HLA Nomenclature Committee pointed out that any new HLA specificity must be based on the corresponding DNA sequences, otherwise it will no longer be named. The detection methods of HLA-B27 include micro lymphocyte cytotoxicity test (MLCT), flow cytometry and molecular biology methods (PCR), of which MLCT may cause false positives due to the number or structure of B27 molecules on the surface of cell membranes altered by infections and other factors; flow cytometry has a relatively better specificity and sensitivity, but the results of the reagents in the Department of Laboratory Science are often only reported as negative and positive, and the percentage of positive cells, the fluorescence intensity, the number of positive cells, and the number of positive cells are not always reported. The specificity and sensitivity of flow cytometry are relatively good, but the laboratory often only reports negative-positive reagent results, while the percentage of positive cells and fluorescence intensity are often ignored; PCR has high sensitivity, but the false-positive rate is also relatively high, which limits the clinical use of the method. The relationship between HLA-B27 and spondyloarthropathies Spondyloarthropathies (SpA) are a group of diseases characterized by chronic progressive inflammation of the mid-axial and peripheral joints and periarticular tissues. This group of diseases is based on the prototypical AS, and the diagnoses that have been recognized or established include AS, reactive arthritis (ReA), psoriatic arthritis (PsA), and inflammatory bowel disease arthritis (IBDA), juvenile spondyloarthropathies (JSpA) and undifferentiated spondyloarthropathies (uSpA). Most SpA patients carry the HLA-B27 gene, especially the spine or sacroiliac joints, which are more closely related to HLA-B27. Although HLA-B27 is closely related to SpA, it cannot be used as the basis for diagnosis, and it is still only a reference for clinical diagnosis or prognosis. The prevalence of HLA-B27 in SpA is not the same for each disease classification: about 90% of AS patients are HLA-B27 positive, more than 70% of ReA patients are HLA-B27 positive, 80% of JSpA, 50% of psoriasis or enteropathy-related arthritis with spondyloarthritic involvement are HLA-B27 positive. In addition, regarding the inheritance of the HLA-B27 gene, there is a 50% chance that the HLA-B27 gene will be passed on to the child, and there is a 20% chance that an HLA-B27-positive child will develop SpA, while an HLA-B27-negative child is very unlikely to develop SpA. In addition, HLA-B27 positivity may indicate that a relative is at risk for this group of diseases, often leading to early diagnosis and treatment of potential patients. Diagnosis of HLA-B27 and SpA 1. HLA-B27 and AS Clinically, many patients or non-rheumatologists would link HLA-B27 to the diagnosis of AS, but in fact, HLA-B27 has not yet been included in the diagnostic criteria of AS. Although the HLA-B27 positivity rate of AS patients reaches about 90%, it does not have the diagnostic specificity because the HLA-B27 positivity rate of the general population can be as high as 8%; the HLA-B27 positivity rate of the general population can also be as high as 8%; the HLA-B27 positivity rate of the general population can also be as high as 8%. Although the rate of HLA-B27 positivity in AS patients reaches about 90%, it is not diagnostic specific, because the rate of HLA-B27 positivity in the general population can be as high as 8%. Although HLA-B27 is closely related to AS, its pathogenic mechanism has not yet been clarified. At present, there are two major hypotheses on the role of HLA-B27 in the development of AS: (1) the autoimmune hypothesis that HLA-B27 delivers antigens to cytotoxic T-cells; and (2) the hypothesis that HLA-B27 misfolds during assembly, leading to endoplasmic reticulum stress and autophagy, but both of them need to be explored in further studies. However, both hypotheses need to be explored in further studies. With the in-depth study of HLA-B27 and AS, some studies have suggested that the clinical manifestations and prognosis of HLA-B27-positive AS patients are relatively more severe than those of negative patients, and some studies have also suggested that specific HLA-B27 isoforms may be associated with some specific clinical manifestations of AS, for example, HLA-B*2705 isoforms are more prone to uveitis than HLA-B*2704 isoforms in AS patients. For example, patients with HLA-B*2705 are more likely to develop uveitis than those with HLA-B*2704. 2. HLA-B27 and axial SpA The International Spondyloarthritis Assessment Working Group (ASAS) recommended the inclusion of HLA-B27 positivity in the classification criteria for axial SpA as early as 2009, which is helpful for the early diagnosis of AS. The 2010 ASAS classification criteria for axial SpA are as follows: 2010 ASAS classification criteria for axial SpA