What provokes juvenile rheumatoid arthritis?

For the first time juvenile rheumatoid arthritis was described at the end of the last century by two well-known pediatricians: the Englishman Stille and the Frenchman Schaffar. Over the next decades in the literature, this disease was referred to as the Still-Shaffar disease.

Symptomocomplex of juvenile chronic arthritis included: symmetrical lesion of joints, the formation of deformations, contractures and ankyloses in them; the development of anemia, enlarged 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 the syndrome of the syndrome revealed much in common between rheumatoid arthritis in adults and children, both in clinical manifestations and in the nature of the course of the disease. However, rheumatoid arthritis in children was also different from the disease with the same name in adults. In this connection, in 1946 two American researchers Koss and Boots proposed the term "juvenile (juvenile) rheumatoid arthritis". The nosological isolation of juvenile rheumatoid arthritis and adult rheumatoid arthritis was subsequently confirmed by immunogenetic studies.

The reason for the development of juvenile rheumatoid arthritis has not been studied sufficiently to date. However, it is known that juvenile rheumatoid arthritis is a disease with a polygenic type of inheritance. Factors of heredity and the environment are involved in its development.

Open a variety of etiological factors. The most frequent among them is a viral or mixed bacterial and viral infection, joint injuries, insolation or hypothermia, vaccinations, especially against or immediately after an acute respiratory viral infection or bacterial infection.

Arthritis caused by an acute viral infection, as a rule, is completely and independently cured. The possible role of infection can be indirectly confirmed by the fact that chronic arthritis is most typical for children with different variants of immunodeficiency states (with selective deficiency of IgA, hypogammaglobulinemia, deficiency of C-2 component of the compliment). In this case, infection is not the direct cause of the development of arthritis, but has the value of the trigger factor of the autoimmune process. The connection of the onset of the disease with the advanced SARS was revealed, with the preventive vaccination against measles, rubella, mumps. It is interesting that the debut of juvenile rheumatoid arthritis after vaccination against mumps is more common in girls. There are cases when juvenile rheumatoid arthritis manifests after vaccination against hepatitis B. The development of juvenile rheumatoid arthritis is also associated with a re-atal infection with the A2H2N2 influenza 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 the development of reactive arthritis, and that only a part of patients with reactive arthritis result in complete recovery. This variant of the flow is characteristic mainly for post-insernosial reactive arthritis and reactive arthritis associated with campylobacter infection. It is known that in most patients after the transferred reactive arthritis, oligoarthritis can later be recycled, and part develops chronic arthritis, which transforms into juvenile spondyloarthritis, juvenile rheumatoid arthritis and even psoriatic arthropathy (PSA). It depends on the etiological factor of reactive arthritis and on the immunological characteristics of the macroorganism, in particular the presence of HLA B27 antigen.

The association of juvenile rheumatoid arthritis with chlamydial infection has not previously been studied. At the same time, there is an increase in the prevalence of chlamydial infection worldwide, and the predominance of chlamydial etiology arthritis among all reactive arthritis. It follows that the role of chlamydial infection in the development and maintenance of chronic inflammation in the joints in 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).

In children with juvenile rheumatoid arthritis, an increase in antibody titre to bacterial peptidoglycans is noted, which indirectly may indicate the role of bacterial infection in the development of this disease. There are also data on the relationship of juvenile rheumatoid arthritis to infection caused by mycoplasma pneumonia.

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

In the world literature there is a large amount of information about associations of histocompatibility antigens with juvenile rheumatoid arthritis in general, and with separate forms and variants of the disease. Immunogenetic risk markers for the development of juvenile rheumatoid arthritis and protective histocompatibility antigens, found in patients with juvenile rheumatoid arthritis, are significantly less likely than in the population. Immunogenetic studies have confirmed the fundamental differences between juvenile rheumatoid arthritis and adult rheumatoid arthritis. Most often as risk markers for the development of juvenile rheumatoid arthritis are called A2, B27, B35. DR5, DR8 antigens. According to the literature, the protective (protective effect) has DR2 antigen.

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

With the greatest degree of probability, reactive arthritis and Bechterew's disease fit into 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. The cross serological reactivity between HLA-B27 and chlamydia, Yersinia was revealed. Salmonella, mycoplasma, campylobacter, which are the cause of development of reactive arthritis and Reiter's syndrome, as well as the Klebsiella, which has a possible etiological role in the development of ankylosing spondylitis. In the case of infection with these microorganisms, the immune system begins to produce antibodies in HLA-B27 carrier that cross-react with their own cells expressing a sufficiently large number of HLA-B27 molecules. Generated in response to infectious antigens, antibodies become antibodies with the further development of an autoimmune inflammatory process.

In conditions of cross-reaction, it is also possible to disrupt the cognition of foreign microorganisms with the further development of a 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 obvious.

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

In the emergence of chronic arthritis, the etiological role of viruses has not been proven. However, the possible significance of Coxsackie, Epstein-Barr virus, parvoviruses in the development of primary-chronic viral infection is suggested. Against the background of immunological defects. The arthritogenic effect of the viral infection in this case is hypothetically associated with class II histocompatibility antigens that present foreign antigens and 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 an intrinsic, altered HLA develops. This mechanism of the relationship of histocompatibility antigens with a predisposition to diseases is designated as a hypothesis of modification of HLA antigens.

Hereditary predisposition to juvenile rheumatoid arthritis is confirmed by family cases of this disease, the results of the study of twin pairs, and immunogenetic data. Most often as markers of risk of development of juvenile rheumatoid arthritis are called antigens A2, B27, less often B35, DR5, DR8.