What triggers juvenile rheumatoid arthritis?

Juvenile rheumatoid arthritis was first described at the end of the last century by two famous pediatricians: the Englishman Still and the Frenchman Shaffar. Over the following decades, this disease was referred to in the literature as Still-Shaffar disease.

The symptom complex of juvenile chronic arthritis included: symmetrical joint damage, formation of deformations, contractures and ankylosis; development of anemia, enlargement of the lymph nodes, liver and spleen, sometimes the presence of febrile fever and pericarditis. Subsequently, in the 30-40s of the last century, numerous observations and descriptions of Still's syndrome revealed much in common between rheumatoid arthritis in adults and in children, both in clinical manifestations and in the nature of the course of the disease. However, rheumatoid arthritis in children still differed from the disease with the same name in adults. In this regard, in 1946, two American researchers Koss and Boots proposed the term "juvenile (adolescent) rheumatoid arthritis". The nosological distinctness of juvenile rheumatoid arthritis and rheumatoid arthritis in adults was subsequently confirmed by immunogenetic studies.

The cause of juvenile rheumatoid arthritis has not been sufficiently studied to date. However, it is known that juvenile rheumatoid arthritis is a disease with a polygenic type of inheritance. Heredity and environmental factors participate in its development.

To discover many etiological factors. The most common among them are viral or mixed bacterial-viral infection, joint injuries, insolation or hypothermia, vaccinations, especially against the background of or immediately after an acute respiratory viral infection or bacterial infection.

Arthritis caused by acute viral infection usually heals completely and on its own. The possible role of infection can be indirectly confirmed by the fact that chronic arthritis is most typical for children with various types of immunodeficiency states (with selective IgA deficiency, hypogammaglobulinemia, deficiency of the C-2 component of complement). In this case, infection is not a direct cause of arthritis, but has the significance of a trigger factor of the autoimmune process. A connection has been found between the onset of the disease and previous ARVI, with preventive vaccination against measles, rubella, and mumps. Interestingly, the debut of juvenile rheumatoid arthritis after vaccination against mumps is more often observed in girls. There are known cases where juvenile rheumatoid arthritis manifested after vaccination against hepatitis B. The development of juvenile rheumatoid arthritis is also associated with peripartum infection with the influenza A2H2N2 virus, as well as infection with parvovirus B19.

The role of intestinal infections, mycoplasma, beta-hemolytic streptococcus in the development of juvenile rheumatoid arthritis is not recognized by most rheumatologists. However, it is known that these infections are the cause of reactive arthritis, and that only some patients with reactive arthritis end in complete recovery. This course of the disease is characteristic mainly of post-yersiniosis reactive arthritis and reactive arthritis associated with campylobacter infection. It is known that most patients after reactive arthritis may subsequently have recurrent oligoarthritis, and some develop chronic arthritis, transforming into juvenile spondyloarthritis, juvenile rheumatoid arthritis and even psoriatic arthropathy (PSA). This depends on the etiological factor of reactive arthritis and the immunological characteristics of the macroorganism, in particular the presence of the HLA B27 antigen.

The relationship between juvenile rheumatoid arthritis and chlamydial infection has not been studied previously. However, there is currently an increase in the prevalence of chlamydial infection worldwide, and the prevalence of arthritis of chlamydial etiology among all reactive arthritis. It follows that the role of chlamydial infection in the development and maintenance of chronic inflammation in the joints of children with juvenile rheumatoid arthritis requires in-depth study. According to our data, about 80% of patients with juvenile rheumatoid arthritis are infected with chlamydia (mainly Cl. pneumoniae).

Children with juvenile rheumatoid arthritis have an increased titer of antibodies to bacterial peptide glycans, which may indirectly indicate the role of bacterial infection in the development of this disease. There is also evidence of a connection between juvenile rheumatoid arthritis and infection caused by Mycoplasma pneumoniae.

Hereditary predisposition to juvenile rheumatoid arthritis is confirmed by family cases of this disease, studies of twin pairs, and immunogenetic data.

There is a large amount of information in the world literature about the association of histocompatibility antigens with juvenile rheumatoid arthritis in general and with individual forms and variants of the disease. Immunogenetic markers of the risk of developing juvenile rheumatoid arthritis and protective histocompatibility antigens have been identified, which are found in patients with juvenile rheumatoid arthritis significantly less often than in the population. Immunogenetic studies have confirmed the fundamental differences between juvenile rheumatoid arthritis and rheumatoid arthritis in adults. The most frequently named markers of the risk of developing juvenile rheumatoid arthritis are A2, B27, B35. DR5, DR8 antigens. According to the literature, the DR2 antigen has a protective effect.

There are a number of hypotheses explaining the relationship between infectious factors and histocompatibility antigens with the development of rheumatic diseases. The most common is the hypothesis of antigen mimicry.

Reactive arthritis and Bechterew's disease most likely fit this model. It is known that the structure of the HLA-B27 antigen is similar to some proteins of the cell membrane of a number of microorganisms. Cross-serological reactivity has been revealed between HLA-B27 and chlamydia, yersinia, salmonella, mycoplasma, campylobacter, which are the cause of reactive arthritis and Reiter's syndrome, as well as with Klebsiella, which is assigned a possible etiologic role in the development of ankylosing spondylitis. In case of infection with these microorganisms, the immune system of the HLA-B27 carrier begins to produce antibodies that cross-react with the body's own cells expressing a sufficiently large number of HLA-B27 molecules. Antibodies produced in response to infectious antigens become antibodies with further development of an autoimmune inflammatory process.

In conditions of cross-reaction, it is also possible that the recognition of foreign microorganisms may be impaired, with the subsequent development of a long-term persistent chronic infection. As a result, the initial defect of the immune response is further aggravated.

The role of viral infection in the development of chronic arthritis is less clear.

It is known that more than 17 viruses are capable of causing an infection accompanied by acute arthritis (including rubella, hepatitis, Epstein-Barr, Coxsackie viruses, etc.).

The etiologic role of viruses in the development of chronic arthritis has not been proven. However, the possible role of Coxsackie, Epstein-Barr, and parvoviruses in the development of primary chronic viral infection is assumed. against the background of immunological defects. The arthritogenic effect of viral infection in this case is hypothetically associated with class II histocompatibility antigens, which present foreign antigens, viruses, to the immune system. However, as a result of the interaction of its HLA receptor with a viral antigen, a neoantigen is formed, which is recognized by the immune system as foreign. As a result, an autoimmune reaction to its own, modified HLA develops. This mechanism of the relationship of histocompatibility antigens with a predisposition to diseases is designated as the hypothesis of modification of HLA antigens.

Hereditary predisposition to juvenile rheumatoid arthritis is confirmed by family cases of this disease, the results of a study of twin pairs, and immunogenetic data. The most frequently used markers of the risk of developing juvenile rheumatoid arthritis are antigens A2, B27, and less often B35, DR5, DR8.