Etiology. The question of the causative agent (agents), which determines the development of immune disorders that underlie RA and YUHA, has so far not been beyond the scope of scientific assumptions. When discussing the infectious factors that could be responsible for the occurrence of these diseases, it is necessary to take into account that they must possess such properties as tropism for articular tissues, the ability to persist in them and cause a characteristic response. Despite the fact that such microorganisms are well known, for example, a group of some pathogens of intestinal infections, however, they can be regarded as a trigger rather than an etiological factor.
Numerous attempts to link the occurrence of UHA and RA with focal infection in the nasopharynx, as well as to prove the etiological role in their development of various types of streptococcus and staphylococcus have led to negative results. In contrast to the roars of mathism, RA and YUHA are not associated with quinsy and chronic tonsillitis. Separate observations about the occurrence of the disease against the background of a nasopharyngeal infection are either coincidental coincidences or indicate only the provocative, predisposing role of this infection.
Attempts to apply “blindly” antibacterial treatments and the bicillin prophylaxis of RA and YUHA did not give positive results and, if not justified, should be abandoned.
At present, it can be argued that no microorganism of a bacterial nature is the causative agent of these diseases. Also of historical importance are works that confirm the etiological role of mycoplasma.
At present, research attention is being drawn to the study of the etiological role of viruses in RA to YUHA. In particular, indirect evidence of the presence of virus-like inclusions in the cells of the synovial membrane of patients detected by electron microscopy supports the viral hypothesis of etiology. However, no one has yet been able to isolate the “rheumatoid virus”. Numerous observations about an increase in the titers of anti bodies to rubella, measles and parainfluenza in the blood of patients with RA and UXA have been described.However, it seems that in these cases we are talking about cross-nonspecific reactions with various viral antigens. In recent years, not the microorganisms themselves have been actively discussed, but the antigenic components of microbial cells, in particular, the peptidoglycans that make up the cell membranes, for example, streptococcus, yersenia, and several other microorganisms. Peptidoglycans are also found in Freund’s complete adjuvant (oil emulsion of dead mycobacteria) used to reproduce chronic arthritis in animals. It is known that antigenic components of microbial cells included nye in immune complexes may be permanently stored in a poppy rofagah, chondrocytes, poorly vascularized areas sous stava (ligament, cartilage), stimulating, especially when constitutional predispositions, inflammatory response, OCU slovlivaya chronic process.
In the occurrence of RA and, especially, YUHA, in addition to infectious agents, some authors attach a certain importance to drug allergy, the administration of protein preparations (for vivka, the administration of gamma globulin, etc.) and traumatic damage to the joints. In any case, the connection of clinical manifestations with the factors listed above in some patients is carried.
Summarizing the data on the study of the etiology of RA and YUHA, it can be noted only a general statement that the provoking effect is always of a nature associated with antigenic stimulation. It seems that the starting factor of immune (autoimmune) inflammation in these diseases may be different. This provision was most precisely formulated by V.A. Sonova: “At present, an understanding of rheumatoid arthritis as a separate nosological form, apparently due to various etiological factors, with a mandatory immunopathological mechanism, is justified.”
Pathogenesis. At present , although the pathogenetic mechanisms of the development of rheumatoid arthritis and juvenile chronic arthritis are not yet fully understood, nevertheless, the pathogenesis of RA is known much better than YUHA. Especially for methodological reasons, it seems to us right to first present the current understanding of the pathogenesis of RA, and in the conclusion of this section, provide data that allow us to consider YUHA as a group of pathology that is somewhat different from RA.
According to modern concepts, rheumatoid arthritis refers to systemic autoallergic diseases with the production of antibodies to the body’s own tissues (autoantibodies). Such mechanisms for the development of the disease determine the progressive nature and systemic nature of the lesion.
In RA, the main links of pathogenesis are associated with reactions of the immunopathological (autoimmune) nature. Hyperplastic changes in the lymphoid apparatus, high B-lymphocyte activity, an increase in the blood immunoglobulin fractions, the appearance of various immune complexes and autoantibodies in the synovial fluid and blood serum, the therapeutic effect of hormonal and immunoregulatory drugs makes it possible to assume that “excited” the state of the immunocompetent system in response to a fairly powerful and long-lasting antigenic stimulation. In this way. The state of increased activity of the immune system is the source of the leading syndrome of arthritis disease .
Clinical, immunological and experimental studies indicate that activation of the immunocompetent system in RA is associated mainly with the humoral link, the activity of the B lymphoid system. One of the most obscure is the question of why such a high activity of B-cells is associated. As is known, the process of antibody production is rather complicated and depends on various factors, the scheme of regulation of which is presented in a somewhat simplified form in the figure .
Currently, in the pathogenesis of activation of the B lymphoid system in rheumatoid arthritis, three main concepts are discussed. According to the first of these, we are talking about the insufficiency of the first link in immunogenesis associated with the activity. Macrophages – their mobility and digestive ability. In these cases, even if a relatively small amount of antigen (infectious or any other) is ingested, the process of elimination of the antigen is disrupted in the body, resulting in a constant circulation and hence hyperproduction, antibodies. This point of view quite satisfactorily explains the long-term chronic infection process, but cannot explain the uncontrolled production of autoantibodies in RA.
Another concept related to the Fidenberg hypothesis is the idea of the presence of immunodeficiency in patients, op-. Gene-controlled immune response. Known on the existence of genes for high or low response to specific antigens. If there is a low immune response to a certain microorganism, a person can not perform a complete immune protection against this microorganism. At the same time, with respect to other antigens, the response will be full. In such a situation, the introduction of a microorganism allows it to parasitize for a long time in a macroorganism. Tissue destruction caused by toxins or other factors leads to the release of tissue antigens. Due to the fact that the immune system is defective only in relation to the microorganism, it actively responds to the released tissue autoantigens. To a certain extent, this concept is confirmed by the study of histocompatibility antigens, which bind the control of the immune response in humans. In adults with rheumatoid arthritis, a significantly higher incidence of DR-4 antigens was detected, but the association with antigen B-27 is most pronounced in diseases such as Bech terev disease, psoriatic arthritis, Reiter’s disease, which by its
His pathogenesis is considered very close to RA adults. However, this point of view, in spite of its attractiveness, cannot satisfactorily explain the constantly progressive nature of the disease, since it implies the constant persistence of an alien microorganism that has a damaging effect on tissue. In any case, the search for such an infectious or other agent did not lead to satisfactory results.
Finally, the last hypothesis was formulated in 1974 after the discovery of T-suppressors, which suppress (decrease) the activity of B-lymphocytes. It is again about immunodeficiency but T-suppressor deficiency, which “dictate” the development of immunological tolerance to B-lymphocytes. After contact with the antigen, B-lymphocytes under the influence of T-suppressors are not transformed into plasma cells, which synthesize antibodies, but are in a state of immunological tolerance. The hypothesis suggests that this is the way to maintain tolerance of the B-system of immunity towards auto-antigens. With a deficiency of T-cynpecors, B – cells begin to react to normal tissue antigens, produce autoantibodies, which provide, in fact, an uncontrolled autoimmune process. The deficiency of the thymus derivative of the suppressor cell population can be congenital, this situation is confirmed by the much more frequent occurrence of RA in the relatives of the patients, and in addition, significantly more
frequent detection of rheumatoid factor in relatives of patients with RA. However, a decrease in the function of T-suppressors is possible under the influence of external factors as well, for example, a well known decrease in the activity of the suppressor apparatus in case of VIRUS infections.
The above concepts allow us to consider RA as an immunodeficient disease, and this deficiency is associated with immunoregulation. Finally, it cannot be ruled out that in the pathogenesis of the development of the disease in a particular patient, not one of the proposed mechanisms takes place, but several, and their place and role may be very different. If such a point of view is allowed, then the diversity of clinical manifestations, the nature of the course and the curability of rheumatoid arthritis becomes clear.
In general, a diagram of the development of the pathological process in RA is shown in fig. 2. It is assumed that in most cases, as a result of the impact of a damaging factor (infection, trauma, vaccinations, etc. ), synovitis that does not have a specific rheumatoid character develops . In the course of the flow of this synovitis, the natural immune reaction, as discussed above, in a certain category of people is accompanied by an uncontrollable _ activation of the B lymphoid system with the formation of rheumatoid immune complexes, which lead to further damage to the joint, destruction of cartilage and bone and transformation pathological process in cyclic, autoimmune. This is probably the moment.