The etiology of AS has not yet been fully elucidated, and in recent years, molecular mimicry has provided a comprehensive explanation of the various aspects of pathogenesis from different perspectives. Epidemiological investigations combined with immunogenetic studies have revealed that HLA-B27 is positive in more than 90% of patients with ankylosing spondylitis, proving that AS is genetically related. Most scholars believe that it is associated with genetic, infectious, immune, and environmental factors. Genetic factors have an important role in the development of AS. According to epidemiological surveys, the rate of HLA-B27 positivity in AS patients is as high as 90%-96%, while the rate of HLA-B27 positivity in the general population is only 4%-9%; the incidence of AS in HLA-B27 positive patients is about 10%-20%, while the incidence in the general population is 1%-2%, a difference of about 100 times. It has been reported that the risk of AS in first-degree relatives of AS patients is 20 to 40 times higher than that of the general population. The prevalence rate of first-degree relatives of AS patients was 24,2% in a domestic survey, which is 120 times higher than that of the normal population. the chance of AS occurring in relatives of HLA-B27-positive healthy people is much lower than that of relatives of HLA-B27-positive AS patients. All these suggest that HLA-B27 is an important factor in the development of AS. However, it should be noted that, on the one hand, not all HLA-B27-positive individuals develop spondyloarthropathies, and on the other hand, approximately 5% to 20% of patients with spondyloarthropathies test negative for HLA-B27, suggesting that other factors besides genetics influence the development of AS, and therefore, HLA-B27 is an important genetic factor in the expression of AS, but not the only factor influencing the disease . There are several hypotheses to explain the relationship between HLA-B27 and spondyloarthropathies: 1, HLA-B27 acts as a receptor site for an infection factor. 2, HLA-B27 is a marker of an immune response gene that determines susceptibility to environmental excitatory factors. 3, HLA-B27 can cross-react with foreign antigens, thereby inducing the development of tolerance to foreign antigens. 4. HLA-B27 enhances neutrophil activity. With the help of monoclonal antibodies, cytotoxic lymphocytes, immunoelectrophoresis and restriction fragment length polymorphism, about 7 or 8 subtypes of HLA-B27 have been identified. there may be genetic differences between healthy HLA-B27 positive individuals and patients with spondylosis, for example, all HLA-B27 positive individuals have a constant HLA-B27M1 antigenic determinant cluster, and antibodies against this antigenic determinant cluster Antibodies against this antigenic determinant can cross-react with HLA-B27. Most HLA-B27 molecules also have M2 antigenic determinants, and HLA-B27M2-negative molecules appear to be more strongly associated with AS than other HLA-B27 subtypes, especially in Asians, where HLA-B27M2-positive subtypes may have an increased susceptibility to Reiter syndrome. It has been shown that two antigenic determinants, HLA-B27M1 and M2, and arthritogenic factors such as Klebsiella, Shigella and Yersinia can cross-react. Those with a low response seem to present mostly with AS, while those with an enhanced response develop reactive arthritis or Reiter syndrome. Recent studies have suggested that the incidence of AS may be related to infection. The carriage rate of Klebsiella enterica pneumoniae and IgA-type antibody titers against this organism in serum were found to be higher in AS patients than in controls during the active phase of AS and were positively correlated with disease activity. It has been suggested that Klebsiella spp. and HLA-B27 may have cross-reactivity between antigenic residues or a common structure, e.g., the HLA-B27 host antigen (residues 72-77) shares a homologous amino acid sequence with Klebsiella pneumoniae (residues 188-193), and it is not clear whether other Gram-negative bacteria share the same sequence. Immunochemical analysis revealed that about 50% of patients with HLA-B27-positive Reiter syndrome had antibodies bound to this synthetic peptide sequence in their sera, and 29% of patients with HLA-B27-positive AS compared with only 5% of controls. According to statistics, 83% of men with AS have a combination of prostatitis, and some scholars have found that about 6% of patients with ulcerative colitis have a combination of AS. Other reports have confirmed that the incidence of ulcerative colitis and restrictive enteritis is much higher in patients with AS than in the general population, so it is speculated that AS may be related to infection. It has been found that 60% of patients with AS have increased serum complement levels, most cases have IgA-type rheumatoid factor, serum C4 and IgA levels are significantly increased, and there are circulating immune complexes in the serum, but the antigenic nature has not been determined. The above phenomena suggest that immune mechanisms are involved in the pathogenesis of the disease. Trauma, endocrine, metabolic disorders and metabolic reactions are also suspected to be factors in the pathogenesis. In conclusion, the etiology of the disease is unknown and no single theory can fully explain all the manifestations of AS. It is likely that the disease is caused by environmental factors (including infection) on the basis of genetic factors. The early histopathological features of the disease are different from those of rheumatoid arthritis, with the basic pathological changes being lesions of tendons and ligamentous bone attachments, and some degree of synovial inflammation may occur. The earliest onset is often in the sacroiliac joint, and later joint adhesions, fibrous and bony ankylosis may occur. The histologic changes are chronic inflammation of the joint capsule, tendons, and ligaments with lymphocytic and plasma cell infiltration. These inflammatory cells are distributed in clusters around smaller synovial vessels. Chronic inflammatory lesions may also be present in adjacent bone tissue, but their inflammatory lesions are not related to the pathological process of the synovium. The disease differs from the pathological changes of rheumatoid arthritis in that there is a tendency for significant calcification of joint and para-articular tissues, ligaments, intervertebral discs and annular fibrous tissue. The histologic changes of peripheral synovitis in this disease also differ from those of rheumatoid arthritis in that the synovial inflammatory plasma cells are predominantly of IgG and IgA types, and there are more lymphocytes in the synovial fluid, and macrophages that have engulfed degenerated polymorphonuclear cells can be seen. Synovial inflammation is rarely associated with extensive erosive and deforming changes. Sacroiliitis is the pathologic hallmark of ankylosing spondylitis and is often one of its earliest pathologic manifestations. Early pathologic changes in sacroiliitis include subchondral granulation tissue formation, histologically visible synovial hyperplasia and aggregates of lymphocytes and plasma cells, lymphoid follicle formation, and plasma cells containing IgG, IgA, and IgM. Erosion of bone and destruction of cartilage follows, followed by progressive replacement by degenerating fibrocartilage and eventually bony ankylosis. The initial damage to the spine is granulation tissue formation at the junction of the fibrous ring of the disc and the vertebral bone rim. The outer layer of the fibrous ring may eventually be replaced by bone, forming a ligamentous osteophyte, and further progression will result in the bamboo-like spine seen on x-ray. Other injuries to the spine include diffuse osteoporosis, destruction of the vertebral body adjacent to the disc margin, squared changes in the vertebral body, and disc sclerosis. Similar pathologic changes in the median joint can be observed in other spondylolisthesis.