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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antigenic variation and strain heterogeneity have been demonstrated for the pathogenic Borrelia species, i.e. B. burgdorferi and the relapsing fever borreliae. In relapsing fever, new borrelia serotypes emerge at a high rate spontaneously, a mechanism that is caused by DNA rearrangements on linear plasmid translocating genes coding for variable major proteins from previous silent to expression sites (i.e. from inner sites to telomeric sites of the plasmid). As a result of this variation, the borreliae escape the immune response of the host, thus leading to the relapse phenomenon. In B. burgdorferi, which is the causative agent of the multisystem disorder Lyme borreliosis, there is also a growing body of findings that antigenic variation is involved in pathogenesis of the disease. Phenotypic variation of strains in vitro concerns the size and the amount of surface-associated proteins (OspA, OspB and pC). There are indications that OspA and OspB truncations are due to deletions within the ospAB operon caused by recombination events, and that OspA/OspB-less mutants lack the 49-kb plasmid that bears the ospAB operon. With the increasing number of isolates obtained from various geographic and biological sources, it became apparent that B. burgdorferi is immunologically and genetically more heterogeneous, as previously believed. The major outer surface proteins OspA and OspB (which have been efficient antigens in vaccine studies) are heterogeneous at a genetic level. The same degree of genetic non-identity was observed for the pC protein. Other proteins like flagellin and the highly specific immunodominant p100 range protein show a lower degree of non-identity. Recombinant OspA, pC, p100 range protein and flagellin have been hyperexpressed in E. coli and these proteins are immunologically reactive. This allows further research for development of vaccines and diagnostic tools. B. burgdorferi isolates have been investigated with genotyping (DNA hybridization, PCR and 16S rRNA analysis) as well as serotyping by various authors. Comparison of the different methods has shown good agreement when the same strains have been investigated. No correlation could be found between different phenotypic and genotypic groups with respect to the ability to cause arthritis in SCID mice. A serotyping system based on immunological differences in OspA detected by a panel of monoclonal antibodies has been proposed. Serotyping a large number of B. burgdorferi isolates has shown a striking predominance of the OspA serotype 2 among European isolates from human skin, in contrast to isolates from ticks or CSF.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antigenic variation and strain heterogeneity in Borrelia spp. 147 19

We describe the adoptive transfer of erosive arthritis to an immunodeficient host. Spleen cells from arthritic DBA/1 mice (H-2q), immunized 4-6 weeks previously with bovine type II collagen in adjuvant, were transferred intraperitoneally into SCID mice (H-2d). SCID recipient mice also received native or denatured type II collagen (100 micrograms intraperitoneally) at the time of cell transfer. Arthritis developed in five out of five mice approximately 2 weeks after injection of cells plus native collagen, whereas animals injected with cells plus denatured collagen did not show any clinical or histological evidence of arthritis. The minimum graft size required for successful transfer of arthritis was established at 10(7) DBA/1 spleen cells. Histological examination of the joints of arthritic SCID recipient mice revealed synovitis, fibrosis and erosion of cartilage and underlying bone. Mean circulating levels of anti-type II collagen IgG were found to be significantly higher in mice injected with native collagen than those injected with denatured collagen (40 micrograms/ml and less than 1 microgram/ml, respectively). The ability to transfer collagen-induced arthritis adoptively should facilitate the study of the cellular requirement and pathological mechanisms involved in the induction of this arthropathy.
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PMID:Successful transfer of collagen-induced arthritis to severe combined immunodeficient (SCID) mice. 160 30

Viable Borrelia burgdorferi (B. burgdorferi) organisms induce a chronic infection associated with arthritis, carditis and hepatitis in severe combined immunodeficiency (scid) mice but not in most of the adult mice from the various immunocompetent inbred strains tested. Furthermore, we have found that experimental inoculation of normal mice with B. burgdorferi organisms leads to the generation of antibodies and T cells specific for various spirochetal antigens including the outer surface proteins A and B (OspA, OspB) as well as flagellin. The assumption of a protective role of the immune response during B. burgdorferi infection in mice is supported by our recent findings that passively transferred B. burgdorferi-specific immune mouse sera as well as monoclonal antibodies to OspA are able to prevent the development of the disease in scid mice. We show now that purified OspA protein both in its native and recombinant form is immunogenic and that the antibodies generated are able to confer protection to scid mice against B. burgdorferi infection.
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PMID:A mouse model for Borrelia burgdorferi infection: pathogenesis, immune response and protection. 204 47

The authors describe the histopathologic evolution of Lyme disease in severe combined immunodeficiency (scid) and normal C.B-17 and C57BL/6 mice inoculated with Borrelia burgdorferi. Starting on day 7 after inoculation, all scid mice infected subcutaneously in the tail with a low-passage European tick isolate of B. burgdorferi had clinical evidence of arthritis characterized by reddening and swelling of tibiotarsal joints. Later on, other joints, ie, metatarsal and ulnacarpal joints were also affected. The infection of scid mice resulted in a persistent spirochetemia and the development of a multisystem disease with chronic progressive inflammation of joints, heart, and liver. Major histopathologic alterations included 1) severe joint lesions, characterized by the presence of hyperplastic inflamed synovial lining cells associated with the erosion and destruction of cartilage and/or bone; 2) pancarditis with infiltrations of mononuclear cells in the endocardium, myocardium, and pericardium; and 3) hepatitis with mononuclear cell infiltrations confined to the portal field and central vein, granulomatous reactions, and eventually the development of liver fibrosis. In addition, smaller more confined lesions were found in kidneys, lung, brain, and striated muscle. The inflammatory infiltrates in the various organs were associated mostly with Mac-1+ cells, largely monocytes and macrophages, as well as some polymorphonuclear leukocytes, but not B and T lymphocytes. Infective spirochetes could be readily isolated from blood and joints and were found at the site of inoculum and the myocardium. In contrast, subcutaneous inoculation of normal C.B-17 or C57BL/6 mice with spirochetes in general did not result in clinical signs of arthritis. Only 10% to 20% of the C57BL/6 mice, but none of the C.B-17 mice, showed clinical evidence of oligoarthritis, which appeared not before day 36 after inoculation. In general, the infection of normal mice resulted in minimal lesions in various organs, and no spirochetes could be visualized or reisolated from their tissues. The data demonstrate that Lyme borreliosis may develop in mice in the absence of detectable specific B and T cells and thus suggest an immunologic control of the disease in this species. The scid mouse model therefore can be used to define the components of the immune system responsible for the suppression and/or the progression of the disease.
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PMID:Lyme borreliosis in the severe combined immunodeficiency (scid) mouse manifests predominantly in the joints, heart, and liver. 222 Oct 14

We have recently shown that viable Borrelia burgdorferi organisms induce a chronic infection associated with arthritis and carditis in severe combined immunodeficiency (scid) mice but not in immunocompetent mice. The disease is similar to that found in patients suffering from Lyme disease. We now show that B. burgdorferi-specific immune mouse sera as well as a monoclonal antibody to the spirochetal outer surface antigen A (31 kDa) but not monoclonal antibodies specific for the 41-kDa antigenic component of the periplasmic flagella are able to prevent (or mitigate) the development of the disease in scid mice when passively transferred at the time of the bacterial inoculation. The identification of a B. burgdorferi-associated protective antigen suggests that the corresponding spirochetal protein should be tested as a vaccine against Lyme disease.
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PMID:Monoclonal antibodies specific for the outer surface protein A (OspA) of Borrelia burgdorferi prevent Lyme borreliosis in severe combined immunodeficiency (scid) mice. 233 19

We report that the spirochete B. burgdorferi induces progressive polyarthritis and carditis in mice with severe combined immunodeficiency syndrome (scid) but not in normal C.B-17 mice. The onset and severity of the disease were dependent on (a) the viability; (b) the infectivity; and (c) the dose of inoculated B. burgdorferi organisms. Infective spirochetes were isolated from both blood and joints of inoculated scid mice. These findings suggest that B. burgdorferi-induced chronic arthritis and carditis in mice develops independently of lymphocyte function and makes the scid mouse an attractive laboratory model to study the role of the immune system in experimental Lyme Borreliosis.
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PMID:The severe combined immunodeficiency (scid) mouse. A laboratory model for the analysis of Lyme arthritis and carditis. 279 62

The expression of adhesion molecules on endothelia was examined during chronic arthritis and carditis in SCID and immunocompetent susceptible AKR/N mice infected with Borrelia burgdorferi (B. burgdorferi). All stages of disease were associated with the upregulation or new expression of ICAM-1 and P-selectin and of VCAM-1 and E-selectin, respectively, on blood vessels of affected joint tissues of SCID and AKR/N mice as well as on heart tissue of SCID mice but not in other tissues. Moreover, ICAM-1 was also found on infiltrating mononuclear cells. The overall staining intensity for each of the four adhesion molecules on individual tissue sections of joint and heart increased with time of infection and was associated with the presence of spirochetes in the tissue. In addition it is shown that in both mouse strains inflammation of joints but not heart is accompanied by vascular proliferation. Synovial but not heart tissues of infected SCID mice were found to express both peripheral- (PNAd) and mucosal (MAdCAM-1) lymph node high endothelia venule associated vascular addressins as detected by mAb Meca-79 and Meca-367, respectively, but only at later stages of the disease and only on newly generated small venules. However, neither of the two addressins were evident in synovial lesions of AKR/N mice. Together the data suggest that the concomittant induction of ICAM-1, VCAM-1, E-selectin and P-selectin in lesions of infected mice provide a means for enhanced cellular infiltration into affected organs and that the regulation of these structures is conserved in the absence of a functional immune system. Furthermore, the differential induction of vascular proliferation in joint and heart tissues as well as the restricted expression patterns of vascular addressins indicate that the pathogenetic processes induced by B. burgdorferi are distinct for joint and heart.
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PMID:Expression of endothelial cell adhesion molecules in joints and heart during Borrelia burgdorferi infection of mice. 753 17

Two new models for the study of rheumatoid arthritis have been established. SCID (severe combined immunodeficient) mice implanted with human synovial tissues and human HLA-DR4-CD4 transgenic mice represent novel and important approaches to the use of animal models in pathogenetic studies. New studies of streptococcal cell wall arthritis in rats demonstrated that beta 1 integrin-mediated cell-matrix interactions are involved in the induction and perpetuation of inflammatory synovitis and that systemic administration of interleukin-4 selectively suppresses established synovitis, presumably by effects on monocyte function. The importance of nitric oxide as a mediator of synovial inflammation was confirmed in the adjuvant-induced model of rheumatoid arthritis. In the collagen-induced arthritis model, interesting new data have implicated gamma delta T cells in the pathogenesis of arthritis, and the antineoplastic drug taxol was shown to have anti-inflammatory effects.
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PMID:Animal models in rheumatoid arthritis. 761 11

Previously we have found that sera from immunocompetent mice infected either naturally by ticks or experimentally with low numbers of Borrelia burgdorferi ZS7 bacteria lack OspA- and OspB-specific antibodies but confer optimal protection on severe combined immunodeficiency mice against challenge with spirochetes (U.E. Schaible, L. Gern, R. Wallich, M. D. Kramer, M. Prester, and M. M. Simon, Immunol. Lett. 36:219-226, 1993). We have now used the latter immune sera to identify new spirochetal structures with relevance for protection from an expression library of the virulent European strain B. burgdorferi ZS7. Here we report the cloning and characterization of a novel lipoprotein, designated pG, the gene for which is located on a 48-kb linear plasmid. Sequence analysis of the pG gene revealed an open reading frame encoding a putative lipoprotein of 196 amino acids with a calculated molecular mass of 22 kDa and a consensus cleavage sequence (Leu-X-Y-Z-Cys) recognized by signal peptidase II. Restriction fragment length polymorphism analyses of pG derived from independent B. burgdorferi isolates from different geographic areas revealed that the gene is species specific, with, however, extensive genotypic heterogeneity. Comparison of the protein sequence of pG with those of other known B. burgdorferi outer surface lipoproteins (OspA to OspF and P27) demonstrated that pG is most related to OspF. Furthermore, the upstream region of pG exhibited extensive sequence homology (> 94%) with the ospEF promoter region. Mouse immune sera to recombinant pG did not recognize a corresponding molecule in lysates of in vitro-propagated ZS7 spirochetes. However, experimental or natural infection of mice with ZS7 resulted in the induction of antibodies with reactivity for pG and the potential to delay the development of clinical arthritis. Together with the finding that sera from Lyme disease patients also contain antibodies to pG, our data suggest that the pG gene is preferentially expressed in the mammal environment.
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PMID:Molecular cloning and immunological characterization of a novel linear-plasmid-encoded gene, pG, of Borrelia burgdorferi expressed only in vivo. 764 61

Collagen-induced arthritis (CIA) can be transferred from DBA/1 to SCID mice when native type II collagen (CII) is administered together with spleen cells, arthritis appearing some 14 days after cell transfer. In the present study, we demonstrate that both donor T- and B-lymphocyte populations play a role in this model, and that arthritis arises in SCID recipients of either murine or bovine native CII. Furthermore, the requirement for administration of soluble native CII can be replaced by subarthritogenic doses of serum from Wistar rats with CIA. In this case a fully developed arthritis appears as early as 2 days after cell transfer. However, protein G-purified IgG from CIA rat serum together with splenocytes from arthritic DBA/1 mice does not transfer arthritis. A key role of B cells in this model appears to be the production of a humoral arthritogenic factor since arthritis can be successfully transferred to SCID mice by CIA rat serum administered together with a B cell-depleted splenocyte population consisting of T cells and donor-histocompatible antigen-presenting cells. By contrast, transfer of disease cannot be achieved by co-administration of CIA rat serum and purified donor T cells, indicating that the presence of donor antigen-presenting cells is a requirement for adoptive transfer of arthritis. We propose that joint damage initiated by arthritogenic product(s) of the B cell lineage releases soluble antigens that are presented to T cells which perpetuate the disease. The finding that arthritis can be generated in SCID recipients of CIA rat serum together with splenocytes from non-arthritic DBA/1 mice immunized with denatured CII supports the hypothesis that T cells with specificity for denatured joint components perpetuate disease initiated by humoral factors.
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PMID:The role of the B cells in the adoptive transfer of collagen-induced arthritis from DBA/1 (H-2q) to SCID (H-2d) mice. 770 6


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