Causes and pathogenesis of juvenile ankylosing spondylitis

The cause of juvenile spondylitis is unknown, the cause of the development of this pathology is obviously polyethiologic.

The modern level of knowledge is limited by the understanding of predisposing factors and individual links of pathogenesis. In the origin of this disease, the combination of genetic predisposition and environmental factors is important. Among the latter, the most important role is played by infections, primarily some strains of Klebsiella, other enterobacteria, and also their associations interacting with antigenic structures of the macroorganism, for example, HLA-B27 antigen. The high carrier frequency of this antigen (70-90%) in patients with juvenile spondyloarthritis, compared with 4-10% in the population, confirms the role of HLA-B27 in the pathogenesis of the disease.

Several theories have been suggested that explain the involvement of HLA-B27 in the pathogenesis of juvenile spondylitis.

• "Theory of two genes", indicating the presence of a hypothetical "ankylosing spondylitis gene" located near HLA-B27 on chromosome 6.
• "Theory of one gene", based on the presence of structural similarity of HLA-B27 with a number of infectious pathogens, represented by several options:
  • receptor theory;
  • a hypothesis of cross tolerance or simple molecular mimicry;
  • plasmid hypothesis;
  • the theory of the altered immune response.

At the same time, there is still no more or less logical explanation for the development of ankylosing spondylitis and SAS in B27-negative individuals, and attempts to find other antigens cross-reacting with HLA-B27, the so-called B7-CREG ("cross reactive group"), antigens, also did not clarify this issue.

Confirmation of the hereditary nature of ankylosing spondylitis and juvenile spondylitis - another VM Bekhterev the tendency to accumulation of diseases from the spondyloarthritis group in families of patients with juvenile spondylitis. So, according to the observations of the children's clinic of the Institute of Rheumatology of the Russian Academy of Medical Science, 20% of patients had repeated cases of the disease in the family, and in one third of such families, two of its members were sick. It is important to emphasize that among patients with hereditary ankylosing spondylitis, approximately the same number of HLA-B27-negative patients (about 15%) were observed, as compared with the SAC in general. Proof of the genetic relationship of the entire spondyloarthritis group is a high percentage of repeated cases of these diseases in a variety of combinations in families of patients with juvenile spondyloarthritis, and this is more characteristic of adolescent patients than adults.

Other endogenous factors that play a significant role in the pathogenesis of adolescent spondyloarthritis include neuroendocrine, especially imbalance of sex hormones, possibly explaining the predominant incidence of adolescent spondyloarthritis in males and the most frequent development of the disease in adolescence.

Great importance in the emergence of juvenile spondyloarthritis has a premorbid background. Attention is drawn to the relatively high incidence of multiple signs of connective tissue dysplasia, incl. Anomalies in the structure of bones, hernias of different locations, cryptorchidism, etc. In 2/3 of the patients, the onset of the disease is preceded by the effect of any provoking factor, usually trauma and / or hypothermia.

In the absence of indications of a chronological association of the disease with direct injury to the joint, chronic traumatization of the joint and ligamentous apparatus may have a significant effect, especially when practicing power sports, martial arts, popular in recent years among children and adolescents.

The interaction of genetic and environmental factors triggers a complex cascade of immunological reactions, the feature of which is the predominance of CD4 ⁺ lymphocyte activity and the imbalance of CD8 ⁺ cells responsible for the elimination of bacterial antigens. This leads to the development of many pro-inflammatory cytokines, whose spectrum in juvenile spondyloarthritis is somewhat different from rheumatoid arthritis and besides TNF-alpha tumor necrosis factor, TNF-beta includes interferon y, IL-4, IL-6, IL-2. The increased production of IL-4, which, according to some data, is a stimulator of fibroplastic processes, appears to be one of the causes of fibrosis, which causes the development of ankylosis.

The main morphological substratum of pathological changes in juvenile ankylosing spondylitis (as well as in spondyloarthritis as a whole) is the development of inflammation in the area of enthesis (the places of attachment of joint capsules, ligaments and tendons, fibrous parts of intervertebral discs to bones), whereas synovitis, in contrast to rheumatoid arthritis, is considered as a secondary process. Scientific research of recent years using MRI presented evidence of this long-noted phenomenon. Characteristic for juvenile ankylosing spondylitis, lesion of inactive joints (sacroiliac, intervertebral, symphysis, etc.), as well as hip, different from other peripheral joints, features of vascularization, with the development of inflammatory changes in them leads to chondroid metaplasia of joint capsules and synovial membranes, followed by their ossification and ankylosis.

[1], [2], [3], [4], [5], [6]