What causes reactive arthritis?

Currently, reactive arthritis refers mainly to diseases associated with intestinal and genito-urinary infections associated with histocompatibility antigen B27 (HLA-B27).

Two groups of arthritis:

• genito-urinary;
• postterocolitic.

Causes of urogenital reactive arthritis:

• chlamydia trachomatis (Cl. Trachomatis, serovar D, K);
• ureaplasmas.

The causes of post-enterocolitis reactive arthritis:

• Yersinia ( Y. enterocolitica serotype 03 and 09, Y. Pseudotuberculosis);
• salmonella (S. enteritidis, S. Oranienburg, S. Typhimurium);
• shigella (S.flexneri 2-2 a);
• Campylobacter spp. (Campylobacterjejuni).

Respiratory tract infections associated with Mycoplasma pneumonia and especially Chlamydia pneumonia are common causes of reactive arthritis.

There is evidence of a relationship between reactive arthritis and intestinal infection caused by Clostridium difficile and some parasitic infections. However, there is no data on the relationship of these reactive arthritis with HLA-B27.

Currently, one of the most common causes of development of reactive arthritis is Chlamydia infection. In the structure of reactive arthritis chlamydial arthritis is up to 80%.

Sources of infection in chlamydia - people, mammals, birds. The infection of human S. pneumoniae and S. psittaci occurs by airborne and airborne dust. C. trachomatis is transmitted by the sexual, vertical, contact-household way, when the fetus passes through the infected birth canal of the mother. In childhood, the sexual way of transmission is not relevant. Reactive arthritis can develop if all types of chlamydia are infected.

Immune response to the introduction of a microorganism:

• activation of macrophages;
• local secretory IgA formation (half-life 58 days);
• activation of cellular immunity;
• development of IgM class antibodies against chlamydial lipopolysaccharide (rodospecific antigen) within 48 hours after infection (half-life of 5 days);
• synthesis of IgG antibodies against chlamydial lipopolysaccharide from the 5 th to the 20 th day after infection (half-life of 23 days);
• synthesis of antibodies of class IgG to the main protein of the outer membrane (species-specific antigen) after 6-8 weeks.

In patients with chronic chlamydial reactive arthritis, anomalies of the immune response are revealed: a violation of the ratio between T-suppressors and T-helpers (a decrease in the number of T-helpers), a marked decrease in the relative and absolute number of B cells, and a decrease in the number of natural killer cells.

All changes in the immune response of the patient's organism contribute to the chronization of the process. In the implementation of the genetically determined predisposition of the individual to the development of reactive arthritis, the carriage of HLA-B27 is isolated.

In the development of the disease, the infectious (early) and autoimmune (late) phases are isolated.

Stages of development of chlamydia

Infection - the causative agent on the mucous membranes.

Primary regional infection is the primary lesion of target cells. In this process, two different forms of microorganism (the elementary and reticular bodies) participate. Lasts 48-72 hours.

Process Generation:

• hematogenous and lymphogenous spread of the pathogen;
• Multiple lesion of epithelial cells;
• the emergence of clinical symptoms.

Development of immunopathological reactions, mainly in children with HLA-B27.

The outcome of the infectious process. The process can stop at one of the phases:

• Residual phase (morphological and functional changes in organs and systems are formed, causative agent is absent);
• phase of chronic chlamydia;
• phase of immune autoaggression.

The immune response

The immune response to the introduction of a microorganism is represented by the following actions: activation of macrophages; local secretory IgA formation (half-life 58 days); activation of cellular immunity; production of IgM antibodies against chlamydial lipopolysaccharide (rodospecific antigen) within 48 hours after infection (half-life of 5 days). There is also a synthesis of antibodies of class IgG against chlamydial lipopolysaccharide between 5 and 20 day after the battle (half-life of 23 days); synthesis of antibodies of class IgG to the main protein of the outer membrane (species-specific antigen) after 6-8 weeks.

The development of antibodies, as well as phagocytosis by macrophages is possible only when the chlamydial cell is in the stage of the elementary body in the intercellular space. To completely get rid of chlamydia antibodies is not enough. When chlamydia is in the stage of the reticular body inside the cell, it is absolutely inaccessible for both antibodies, and for lymphocytes and macrophages. Therefore, with a sluggish current or asymptomatic process, the amount of antibodies in the blood is usually small.

In patients with chronic chlamydial reactive arthritis, anomalies of the immune response are revealed, namely: a violation of the ratio between T-suppressors and T-helpers (decrease in the number of T-helpers), a marked decrease in the relative and absolute number of B cells, and a decrease in the number of natural killer cells.

All these changes in the immune response of the patient's organism contribute to the development of the chronization of the process.

Pathogenesis of reactive arthritis

In the origin of reactive arthritis associated with intestinal infection, the main importance is given to infection and genetic predisposition. However, the true nature of the relationship between micro- and macroorganism is still not clear.

"Arthritogenic" microorganisms penetrate into the intestinal mucosa and multiply within polymorphonuclear leukocytes and macrophages. Subsequently, the bacteria and products of their vital activity penetrate from the primary focus into the target organs. According to experimental data, the microorganisms are in the cells expressing HLA-B27 for the longest time.

The role of HLA-B27 in the development of reactive arthritis is not fully understood. This antigen is classified as a class of antigens of the leukocyte antigen of the main complex of human histocompatibility (HLA) found on the surface of most cells of the body (including lymphocytes, macrophages) and involved in the realization of the immune response. It is suggested that HLA-B27 causes the development of an abnormal immune response to the pathogenic intestinal and urogenital microflora. In the serum of patients, antibodies that cross-react with HLA-B27 are sometimes detected. The histocompatibility antigen B27 gives cross-section serological reactions with chlamydia and some gram-negative enterobacteria, which is caused by the phenomenon of microbial antigenic mimicry. According to this hypothesis, proteins that contain structurally similar HLA-B27 molecules are found in the cell wall of a number of intestinal bacteria and chlamydia. It is assumed that cross-reacting antibodies can have a damaging effect on the body's own cells expressing a sufficient number of HLA-B27 molecules. On the other hand, it is believed that such a cross-reaction prevents the implementation of an adequate immune response against intracellular parasites and their effective elimination, contributing to the persistence of the infection.

The importance of genetic factors in the pathogenesis of reactive arthritis is evidenced by their close association with HLA-B27 detected in urinary arthritis in 80-90% of cases and somewhat less frequently with postterocolitic arthritis (the hypothesis of microbial mimicry).