Pathogenesis of Yersinia‐Triggered Reactive Arthritis: Immunological, Microbiological and Clinical Aspects

Abstract

When a patient develops reactive arthritis after Yersinia enteritis, the following conditions are often fulfilled: the patient is HLA-B27-positive; however, some B27-negative individuals develop severe arthritis and some positives do not, in the initial phase, the diarrhea is milder, the anti-Yersinia antibody response of IgG class is more vigorous and persists longer, the anti-Yersinia antibody response of IgA class is more vigorous and persists much longer, the anti-Yersinia antibodies of IgA1 and IgA2 subclass, those with J-chain and, especially, those with secretory piece are produced more vigorously, indicating local immunostimulation close to the intestinal epithelium, in the early phase, Yersinia-IgM immune complexes are found in the circulation, and the lymphocyte transformation response against not only Yersinia but also against other gram-negative enteric bacteria is weaker. When all these aspects are considered together a strong suspicion arises that the patients who are destined to develop reactive arthritis fail in their first line of defense against the invading organism when contracting a Yersinia enteritis. This may lead to persistence of the microorganism within the body, e.g., in the intestinal epithelium or in the mesenteric lymphoid tissues, maintaining a stimulus for a prolonged--apparently futile and perhaps harmful--antibody production. Finally, the initiating and decisive factor should not be forgotten: the Yersinia. Why and how it triggers the process is at present one of the enigmas of the pathogenesis of reactive arthritis.

Immunoblot analysis of IgM, IgG, and IgA responses to plasmid encoded released proteins of Yersinia enterocolitica in patients with or without yersinia triggered reactive arthritis.

“…Occasionally, this primary infection triggers secondary complications such as reactive arthritis. [1][2][3] The mechanisms of the development of yersinia triggered arthritis are not known, but evidently both host related and bacteria related factors are involved.…”

Intestinal infection of BALB/c mice with Yersinia enterocolitica O9 causes major modifications in phenotype and functions of spleen cells

“…Non-septic sequelae of human yersiniosis include reactive arthritis, erythema nodosum, Reiter's syndrome, autoimmune thyroiditis and other immunopathological complications (Winblad, 1973 ;Bech et al, 1974 ;Toivanen et al, 1985). Alterations in the immune networks following infection with a number of microorganisms are likely to play a role in the genesis of immunopathological diseases (Schwartz, 1993).…”

“…Extraintestinal and systemic infections are most often caused by strains belonging to so-called highvirulence serotypes, such as serotype O8 (Heesemann et al, 1993), although low-virulence serotypes, such as O3 and O9, may occasionally cause bactaeremia in patients with iron overload or other underlying diseases (Rabson et al, 1975 ;Bouza et al, 1980). The presence of a 70 kb plasmid (pYV) that carries a number of virulence genes is required for Y. enterocolitica strains to become virulent (Cornelis et al, 1998).Non-septic sequelae of human yersiniosis include reactive arthritis, erythema nodosum, Reiter's syndrome, autoimmune thyroiditis and other immunopathological complications (Winblad, 1973 ;Bech et al, 1974 ;Toivanen et al, 1985). Alterations in the immune networks following infection with a number of microorganisms are likely to play a role in the genesis of immunopathological diseases (Schwartz, 1993).…”

Yersinia-hsp60-reactive T cells are efficiently stimulated by peptides of 12 and 13 amino acid residues in a MHC class II (I-Ab)-restricted manner

“…Clinical manifestations caused by this pathogen range from enteritis, enterocolitis, and mesenteric lymphadenitis to systemic infection with abscesses and granulomatous lesions [1,2]. Furthermore, Yersinia-triggered reactive arthritis is a well known immunopathological complication of intestinal yersiniosis which is frequently observed in patients with HLA-B27 [3,4].…”