Cationic Yersinia antigen-induced chronic allergic arthritis in rats. A model for reactive arthritis in humans.

Abstract

Cationic antigens are known to have considerable arthritogenic potential in experimental systems. During a systematic search for suitable, naturally occurring candidates an intracellular protein was isolated from the ribosomal pellet of Yersinia enterocolitica 0:3, a bacterial strain associated with reactive arthritis in humans. The protein is highly cationic, contains two 19-kD polypeptide chains linked by a disulfide bond, and reveals a strong tendency for spontaneous aggregation. It is suggested to be a nucleic acid binding protein. We tested this antigen for its ability to induce arthritis after intra-articular challenge in preimmunized rats. An acute inflammatory phase followed by transition to chronicity was observed both by technetium-99m scintigraphy and from histology. Massive polymorphonuclear leucocyte infiltration of the synovium was seen early on and fibrosis and thickening of the joint capsule occurred in later stages. Control groups showed no evidence of inflammation. Western blot and ELISA analysis of unselected sera from Yersinia enterocolitica 0:3-infected patients revealed antibodies to the antigen in the majority of cases, whereas healthy individuals rarely reacted. This is the first report of a naturally occurring cationic antigen capable of inducing immunologic tissue injury; it justifies the speculation that cationic antigens from prokaryotic cells could trigger reactive arthritis.in humans. (J. Clin. Invest. 1991. 87:632-642.)

Outer surface lipoproteins ofBorrelia burgdorferivary in their ability to induce experimental joint injury

“…The model used here, known as antigen-induced allergic arthritis, allows individual testing of selected substances. Cationic molecules are particularly effective in this experimental setting (24), which has, in part, been attributed to their prolonged persistence following attachment to anionic structures in the joint, as originally shown for chemically cationized antigens (20,22), and subsequently extended to a cationic antigen from the bacillus Yersinia enterocolitica (25). In the case of B burgdorferi, both individual OSPs and the OSP complex originally prepared by butanol extraction are cationic (26).…”

Perpetuation of inflammation associated with experimental arthritis: the role of macrophage activation by neutrophilic myeloperoxidase

“…With re spec t to prolonge d pre senc e of this enzyme and the induction of RA, it has be e n re ported that highly cationic mole cules have be e n as sociated w ith re te ntion in joints and arthritogenic ity. 23 Re te ntion is be lie ve d to be due to the inte rac tion of the cationic molec ule w ith the ne gatively charged cartilage . 23 ,34 ,3 5 Since this study involve d re peate d inje ctions of various tre atments into a partic ular joint, there w as conc ern that the trauma alone of re peated inje ctions could induce inflammation associate d w ith RA.…”

Construction of Urease-Negative Mutants of Yersinia enterocolitica Serotypes O:3 and O:8: Role of Urease in Virulence and Arthritogenicity

“…The Yersinia 19-kDa urease ␤ subunit has, however, been used to study synovial T-cell response, indicating that this particular antigen still is considered to be of arthritogenic interest (16). Our experimental arthritis resembles human Yersinia-triggered ReA considerably more than does the model used by Mertz et al (15). They induced arthritis by injecting the 19-kDa urease peptide intra-articularly into presensitized rats.…”

“…In the search for arthritogenetic molecules from arthritiscausing bacteria, the urease molecule of Yersinia is of interest because Mertz et al induced arthritis in preimmunized male Wistar rats by intra-articular injection of the 19-kDa ␤ subunit of Y. enterocolitica urease (15,25). Furthermore, the urease ␤ subunit was shown to be a target for the synovial T-cell response of patients with Y. enterocolitica-caused ReA (21).…”

“…Furthermore, the urease ␤ subunit was shown to be a target for the synovial T-cell response of patients with Y. enterocolitica-caused ReA (21). Western blot and enzyme-linked immunosorbent assay analysis of sera from patients suffering from Y. enterocolitica infection revealed antibodies to this antigen (15). Hermann et al found that the ␤ subunit of Yersinia urease is an immunodominant antigen both for proliferative CD4 ϩ T cells and for synovial CD8 ϩ T-cell clones (1,11).…”