Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human class I major histocompatibility complex allele HLA-B27 is associated with a group of human diseases called "spondyloarthropathies." Studies on transgenic rats expressing HLA-B27 and human beta 2-microglobulin have confirmed the role of HLA-B27 in disease pathogenesis. Here we report spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta 2-microglobulin (B27+ beta 2m-/-). In the absence of beta 2-microglobulin, B27+ beta 2m-/- animals do not express the HLA-B27 transgene on the cell surface and have a very low level of CD8+ T cells. Most of the B27+ beta 2m-/- male mice showed nail changes, hair loss, and swelling in paws, which leads to ankylosis. The symptoms occur only after the B27+ beta 2m-/- mice are transferred from the specific pathogen-free mouse colony. These results suggest that aberrant assembly, transport, and expression of the HLA-B27 molecule may predispose an individual for development of the disease when exposed to an appropriate environmental trigger.
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PMID:Spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta 2-microglobulin: a model of human spondyloarthropathies. 756 88

Mycoplasma arthritidis mitogen (MAM) is produced by an organism which can cause chronic proliferative arthritis in rodents. MAM possesses a typical superantigenic activity; it has the ability to activate a large panel of T cells which express specific V beta segments of the T-cell receptor. The presentation of MAM to T cells by antigen-presenting cells is mediated primarily through its binding to the major histocompatibility complex (MHC) class II E alpha chain in mice and the DR alpha chain in humans. However, MAM is much less active for human peripheral blood lymphocytes than for mouse splenocytes. It was suggested that a difference in MAM binding affinity between human and mouse class II molecules may account for their different MAM activities. To examine this possibility, we generated a panel of B-cell transfectants whose DR molecule is composed of either the DR alpha or the E alpha chain paired with a DR3 beta chain. The ability of these transfectants to present MAM to human peripheral T cells was analyzed. Our data show that transfectants expressing E alpha DR beta chimeric molecules have higher MAM-presenting activity than transfectants expressing wild-type DR alpha DR beta molecules, while the latter have higher activity in stimulating DR3-alloreactive T cells. Since both types of transfectants present MAM to T cells expressing the same T-cell receptor V beta gene families, the higher MAM-presenting activity of the E alpha transfectant is not due to its ability to interact with a different set of T cells. Furthermore, both the E alpha 1 and E alpha 2 domains contribute to this increased affinity for MAM binding. Taken together, our data suggest that there may be multiple MAM binding sites on the E alpha and DR alpha chains and residues unique to the E alpha chain may provide additional affinity for MAM.
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PMID:Replacement of the DR alpha chain with the E alpha chain enhances presentation of Mycoplasma arthritidis superantigen by the human class II DR molecule. 764 64

Injection of incomplete Freund's adjuvant (IFA) into the footpads of BALB/c mice induced an acute inflammation. Draining popliteal lymph nodes showed major histocompatibility complex (MHC) class II-restricted proliferation when challenged in vitro with recombinant Mycobacterium bovis 65-kDa heat shock protein (hsp65). alpha beta T cell receptor-positive, CD4+, hsp65-specific T cell lines and clones were generated from these lymph nodes, and 87% of clones responded to a beta galactosidase fusion protein containing residues 238-573 of human hsp60. Seventy percent of these hsp60-responsive clones also responded to a synthetic peptide corresponding to residues 412-423 of the mouse hsp60. This peptide also induced significant responses in IFA-primed lymph node cells but not in lymphoid cells from unimmunized mice. These results demonstrate that T cells specific for epitopes in self hsp60 are activated during inflammatory responses induced in the absence of exogenous bacterial hsp65. The findings of this study may provide a basis for understanding the often reported isolation of mycobacterial hsp65-responsive T cells from inflammatory sites of arthritis patients, and the protective effects of preimmunization with hsp65 in experimental models of arthritis.
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PMID:Inflammation activates self hsp60-specific T cells. 767 30

We have examined the T cell receptor (TcR) expression of clones specific for epitopes of mycobacterial 65-kDa heat-shock protein (hsp65) in the context of two different HLA molecules, and used this system as a model to assess the selection of T cells responsive to this antigen in vivo. DR3-restricted clones were raised from both the synovial fluid (SF) and peripheral blood (PB) of a patient with reactive arthritis in three separate cloning events. Five of five SF-derived clones tested expressed either V beta 5.2 or a closely related beta chain, V beta 5.6. The alpha chains expressed by V beta 5.2+ and V beta 5.6+ clones were from different families, V alpha 2.4 and V alpha 23.2, respectively. Nine of ten clones derived from two cloning procedures on PB taken 3 years later also expressed either V beta 5.2 or V beta 5.6. This suggests that the TcR repertoire for recognizing this major histocompatibility complex/peptide complex is relatively restricted and favors the use of V beta 5. Conservation of the beta chain third complementarity-determining region (CDR3) sequence was not evident, however. Sequencing alpha and beta chains of representative V beta 5.2+ and V beta 5.6+ PB-derived clones revealed TcR which were identical to those utilized by the SF-derived clones, showing that the repertoire for recognition of this antigen is stable over time. Similar studies of TcR expression were carried out on hsp65-specific, DP4-restricted clones derived from the SF of a patient with rheumatoid arthritis by two independent cloning procedures. There was conservation of alpha chain usage, since all clones expressed a member of the V alpha 1 family, but again CDR3 sequence conservation was not apparent. beta chain usage was not restricted since different clones expressed V beta 6.7, V beta 22.3 and V beta 12. Subtle differences in epitope specificity were detected for two clones with differing TcR. Once more, T cell clones with identical alpha and beta TcR chains were obtained from the separate cloning procedures, suggesting oligoclonalty of T cells with this defined specificity in the patient's SF.
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PMID:Restricted T cell receptor expression by human T cell clones specific for mycobacterial 65-kDa heat-shock protein: selective in vivo expansion of T cells bearing defined receptors. 768 83

Chlamydia trachomatis is a major cause of sexually transmitted disease, infertility and reactive arthritis in the Western world, and of trachoma in the developing world. There is evidence that the chronic inflammatory reaction seen in diseases associated with chlamydiae represents a delayed-type hypersensitivity response to chlamydial antigens. Little is known about which chlamydial antigens elicit T-cell responses yet such information could have important implications in terms of both immunopathological understanding of these diseases and immunoprophylaxis design. In this study, 61 chlamydia-specific T-cell clones have been produced from the synovial fluid of an individual with sexually acquired reactive arthritis (SARA). Ten clones have been characterized in detail and used to identify T-cell stimulatory antigens of chlamydiae by means of T-cell immunoblotting. Two distinct antigenic fractions have been identified, one recognized by three of the clones (molecular weight 18,000), the other recognized by six of the clones (molecular weight 30,000). The fractions are distinct from the major outer membrane protein, the 57,000 MW stress protein and the 60,000 MW cysteine-rich membrane protein of chlamydiae. The major histocompatibility complex (MHC) restriction of the response to these antigens differed: clones recognizing the 18,000 MW antigen required antigen-presenting cells expressing DR1 subtype DRB1*0101 or DRB1*0102 which only differ at amino acids 85 and 86 on the DR beta-chain; by contrast clones recognizing the 30,000 MW antigen were presented to only by antigen-presenting cells from DRB1*0101 individuals, reflecting extreme sensitivity of these clones to the polymorphism at positions 85 and 86 on the DR beta-chain.
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PMID:Identification of T-cell stimulatory antigens of Chlamydia trachomatis using synovial fluid-derived T-cell clones. 769 30

This study determined the potential capacity of interleukin-10 (IL-10), compared with IL-4, to control the production of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-1 receptor antagonist (IL-1ra) and the expression of major histocompatibility complex (MHC) class II antigens by monocytes/macrophages isolated from synovial fluid of patients with rheumatoid or other forms of chronic inflammatory arthritis. Mononuclear cells were isolated from synovial fluid and peripheral blood and incubated with or without lipopolysaccharide (LPS), and with or without IL-10 (100 U/ml, 10 ng/ml) or IL-4 (10 ng/ml) for 22 hr. TNF-alpha, IL-1 beta and IL-1ra levels were measured by enzyme-linked immunosorbent assay (ELISA) in the culture supernatants, and MHC class II expression was examined on the monocytes/macrophages by flow cytometry. IL-10, unlike IL-4, decreased TNF-alpha production by LPS-stimulated synovial fluid cells to the same extent as by LPS-stimulated peripheral blood cells from the same patients. IL-10 and IL-4 suppressed equally IL-1 beta production by the same cells. However, only IL-4 significantly increased IL-1ra production by synovial fluid mononuclear cells. Synovial fluid cells expressed increased levels of MHC class II antigen, and these levels were not as efficiently suppressed by IL-10 as they were for peripheral blood cells. Because IL-10 and IL-4 differentially regulate TNF-alpha and IL-1ra production by synovial fluid mononuclear cells, selective use of either IL-10 or IL-4 in the treatment of chronic inflammatory conditions will depend on whether TNF-alpha or IL-1, respectively, is established as primarily responsible for the maintenance of the chronic inflammatory condition.
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PMID:Comparison of the suppressive effects of interleukin-10 and interleukin-4 on synovial fluid macrophages and blood monocytes from patients with inflammatory arthritis. 779 26

Patients with systemic lupus erythematosis (SLE) often manifest features of other autoimmune diseases. In this review, we provide a detailed compendium of features of SLE that overlap with other conditions. This compendium is important because a critical feature in our understanding of autoimmunity has been the clustering of coexisting/different autoimmune diseases both within an affected patient and within a pedigree. Indeed, autoimmune disorders share a variety of similar clinical and serological defects. For example, all autoimmune disorders are associated with the elaboration of autoantibodies and/or the production of self-reactive mononuclear cell populations; many have high levels of immune complexes and defects in cell-mediated immunity. Several diseases share similar genetic backgrounds, as reflected by study of loci within the major histocompatibility complex. In part the coassociation is due to common genetic tendencies with different environmental precipitating agents (trigger mechanisms). It is likely that many factors can modulate the immune system to autoimmunity in the presence of an appropriate genetic background, eg, drugs, viral infections, UV irradiation, and toxins, ie, toxic oil syndrome and L-tryptophan-induced eosinophilic myalgia. The coexistence of SLE with other autoimmune diseases is an excellent venue to understand these events, and we believe that the presence of other autoimmune diseases in patients with SLE can be called the kaleidoscope of autoimmunity.
Semin Arthritis Rheum 1994 Oct
PMID:The coexistence of systemic lupus erythematosus with other autoimmune diseases: the kaleidoscope of autoimmunity. 783 52

HLA class II alleles can protect against immunological diseases. Seeking an animal model for a naturally occurring protective allele, we screened a panel of H2-congenic and recombinant mouse strains for ability to protect against collagen-induced arthritis. The strains were crossed with the susceptible strain DBA/1, and the F1 hybrids immunized with cattle and chicken type II collagen. Hybrids having the H2Ab allele displayed a reduced incidence and duration of the disease. They also had a reduced level of pre-disease inflammation, but not of anti-collagen antibodies. The allele is already known to be associated with reduction of other apparently unrelated immune responses, suggesting that some form of functional differentiation may operate that is not exclusively related to epitope-binding. It is suggested that this may reflect allelic variation in the class II major histocompatibility complex promoter region.
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PMID:Association of H2Ab with resistance to collagen-induced arthritis in H2-recombinant mouse strains: an allele associated with reduction of several apparently unrelated responses. 789 Mar 26

Collagen-induced arthritis (CIA) is an animal model of autoimmune inflammatory polyarthritis that has features similar to rheumatoid arthritis (RA). Much like RA, susceptibility to mouse CIA is influenced by the major histocompatibility complex (MHC), H-2, and restricted to the H-2q and H-2r haplotypes. Whereas the role of the H-2A molecule in susceptibility to CIA is well established, little is known about the role of H-2E molecule in the disease. In this study, we analyzed the effect of a transgenic E beta d molecule on CIA susceptibility in a recombinant mouse B10.RQB3, which expresses the CIA susceptible Aq genes and an Eak gene, but does not produce an E molecule since Ebq is nonfunctional. In the presence of an Ebd transgene, a viable E molecule is generated. Whereas B10.RQB3 were susceptible to CIA, B10.RQB3-E beta d+ showed a dramatic reduction in the incidence of arthritis as well as a decrease in the level of anti-mouse and anti-bovine CII antibodies in their serum. No clear cut differences in the expression of T cell receptor (TCR) V beta was observed between E beta d+ and E beta d- transgenic mice. Mechanisms underlying the protective effect of E beta d transgenic molecule on CIA may shed light on how HLA-DR molecules influence human RA.
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PMID:Protective role of major histocompatibility complex class II Ebd transgene on collagen-induced arthritis. 793 Oct 88

The major histocompatibility complex (MHC) class II region is assumed to influence autoimmune diseases such as rheumatoid arthritis. In the mouse, the H-2q haplotype is associated with susceptibility to collagen-induced arthritis, while the H-2p haplotype is not. The class II A molecules of these haplotypes differ by only four amino acids in the first domain of the beta chain. To test if this difference accounts for the MHC influence on susceptibility to collagen-induced arthritis, H-2p mice were made transgenic with an Abp gene altered to resemble the Abq gene. The transgenic A beta chain hybridized with the A alpha p chain and was shown to be physiologically expressed by testing antigen-presentation capacity to Aq-restricted T cell hybridomas and with FACS analyses. These transgenic mice developed an autoimmune response to type II collagen and also collagen-induced arthritis. The data unequivocally suggest the Ab gene as a major genetic susceptibility locus for autoimmune collagen-induced arthritis.
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PMID:Expression of a transgenic class II Ab gene confers susceptibility to collagen-induced arthritis. 802 30


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