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)

The T cell recognition of type-II collagen (CII) in H-2q mice, susceptible to CII-induced arthritis, was analyzed. With the use of T cell hybridomas derived from rat CII-immunized mice, a peptide corresponding to amino acids 245-270 on chick CII was found to harbor a T cell epitope which is present on heterologous CII (chick, rat, human, and bovine CII) but not on autologous CII. It was shown that this epitope was located within amino acids 260-270, although flanking regions in either direction were necessary for proper recognition. A peptide corresponding to human CII (256-270) was used for further studies. A single amino acid difference at position 266 between mouse CII (aspartic acid) and heterologous CII (glutamic acid) strongly influenced recognition of this peptide. No response towards the mouse peptide was seen with any of the T cell hybridomas. Inhibition studies revealed that the mouse peptide did not bind as well to major histocompatibility complex as the corresponding heterologous peptide. Both peptides gave rise to a T cell response after immunization. However, immunization with the heterologous peptide resulted in a response strictly directed to rat CII and the immunogen while immunization with the autologous peptide elicited T cells which reacted in a heteroclitic fashion, with a stronger response to the heterologous peptide than to the autologous peptide, and did respond to rat CII but not to mouse CII. We suggest that aspartic acid in position 266 results in a cryptic determinant in mouse CII which is neither recognized after CII immunization nor capable of tolerance induction. A glutamic acid at position 266, however, gives rise to an immunodominant epitope which is recognized by a large proportion of the T cells activated after immunization with heterologous CII.
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PMID:Identification of an immunodominant type-II collagen peptide recognized by T cells in H-2q mice: self tolerance at the level of determinant selection. 137 19

Analysis of formal amino acid sequence identity between different TCRB chain (TCRB) hypervariable regions (CDR3) is commonly used to localize relevant sites of TCR antigen interaction or to yield indirect information on unknown corresponding antigens. However, this analysis sometimes fails to demonstrate expected concordances, e.g. between CDR3 from T cell clones of identical reactivity. Since this may be due to ignorance of physico-chemical parameters, we have now use hydropathy profile analysis as an additional method to examine TCRB-CDR3 and putative peptide antigens. Superimposed hydropathy plots (SHOP) of 20 TCRB-CDR3 from HLA-B27-restricted autoreactive and Yersinia enterocolitica-specific synovial cytotoxic T lymphocytes (CTL) isolated from patients with reactive arthritis (ReA) revealed restricted distribution of polar amino acids resulting in characteristically different SHOP profiles between the two CTL groups. Similarly, Yersinia-derived and self nonapeptides known to bind HLA-B27 differed in SHOP profiles. To validate the method we have extended SHOP analysis to published TCRB sequence data from additional TCRB-CDR3 from peptide-specific CTL but not in TCRB from HLA-B27-alloreactive CTL or non-HLA-B27-restricted control CTL. We here demonstrate that SHOP may improve TCR-CDR3 sequence analysis by detection of structural constraints which remain cryptic by conventional sequence analysis. Our data suggest that electrostatic properties rather than rigid sequence motifs determine T cell specificities.
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PMID:TCRB junctional regions from HLA-B27-restricted T cells and HLA-B27 binding peptides display conserved hydropathy profiles in the absence of primary sequence homology. 894 77

We describe 13 adult patients with reactive arthritis induced by tonsillitis. Arthritis occurred 710 days after tonsillitis and involved the wrists, knees, feet and sternoclavicular joints. Some cases had pain in the Achilles tendon areas. Synovial fluid examined in 4 patients was sterile. All patients except 3 showed unequivocal elevation of serum ASO and/or ASK. Streptococcus was isolated from tonsillar swabs in 7 patients. One had maculopapular erythema and 2 had abdominal pain of unknown origin, but none had cardiac involvement, chorea and subcutaneous nodule. HLA examination revealed that 4 had B39 (p <0.005). Eight cases were treated with antibiotics. Five cases underwent tonsillectomy. All tonsils had cryptic abscess. No exacerbation was seen thereafter. These cases probably represent reactive arthritis induced by tonsillitis and should be distinguished from other rheumatic diseases.
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PMID:Reactive arthritis induced by tonsillitis. 908 84

An epitope within the 60 kD Chlamydia trachomatis heat shock protein (hsp) 60, recognized by a HLA-DRB1*0401-restricted T cell clone from a reactive arthritis patient, has been characterized. Stimulatory peptides contained a nine amino acid sequence (residues 38-46) predicted by algorithm to confer strong binding to DRB1*0401, with valine in the P1 position. The overall length of the peptide was critical for efficient recognition; peptides with at least one residue N-terminal to the putative P1 position were markedly more stimulatory than a peptide whose N-terminal is the P1 valine. Optimal responses were seen with 14mer peptides having two to three amino acids N- and C-terminal to the core 9mer. The sequence of the defined epitope is identical in hsp60 from both C. trachomatis and C. pneumoniae. Since the latter is a common respiratory pathogen, patients infected with C. trachomatis may already be primed for responses to hsp60 by prior infection with C. pneumoniae. Such secondary responses are important in the pathogenesis of chlamydia-induced inflammatory diseases such as trachoma. Priming by infection with enteric organisms was considered because of the similarity of the epitope sequence in Escherichia coli hsp60. However, although an E. coli-related peptide was recognized, intact E. coli hsp60 was not, suggesting that the epitope is cryptic in E. coli hsp60. Human hsp60 has six amino acid differences from chlamydial hsp60 in the epitope sequence and was not recognized. Thus cross-reactive recognition of self hsp60 could not be implicated in the pathogenesis of chlamydia-induced reactive arthritis in this patient.
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PMID:Identification and characterization of a DR4-restricted T cell epitope within chlamydia heat shock protein 60. 932 19

We have previously described a fluorescence in situ hybridisation (FISH) assay for the simultaneous analysis of all human subtelomeric regions using a single microscope slide. Here we report the use of this multiprobe FISH assay in the study of a patient whose karyotype was reported by G banding analysis as 46,XX,del(18)(p11.2). Although the proband had some features suggestive of a chromosomal abnormality, relatively few of the specific features of del(18p) were present. She was a 37 year old female with mild distal spinal muscular atrophy (SMA), arthritis of the hands, an abnormal chest shape (pectus excavatum), and an unusual skin condition (keratosis pilaris). Reverse chromosome painting with degenerate oligonucleotide primer-polymerase chain reaction (DOP-PCR) amplified del(18p) chromosomes as a probe confirmed the abnormality as del(18p), with no evidence of any other chromosome involvement. Subsequently, the multiprobe FISH assay confirmed deletion of 18p subtelomeric sequence. However, the assay also showed that sequences corresponding to the 2p subtelomeric probe were present on the tip of the shortened 18p. The patient is therefore monosomic for 18p11.2-pter and trisomic for 2p25-pter, and the revised karyotype is 46,XX,der(18)t(2;18)(p25; p11.2). We believe that a proportion of all cases reported as telomeric deletions may be cryptic translocations involving other chromosome subtelomeric regions. Further studies such as this are necessary to define accurately the clinical characteristics associated with pure monosomy in chromosomal deletion syndromes.
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PMID:Del(18p) shown to be a cryptic translocation using a multiprobe FISH assay for subtelomeric chromosome rearrangements. 973 29

The development of many autoimmune diseases has been etiologically linked to exposure to infectious agents. For example, a subset of patients with a history of Salmonella infection develop reactive arthritis. The persistence of bacterial antigen in arthritic tissue and the isolation of Salmonella or Yersinia reactive CD8+ T cells from the joints of patients with reactive arthritis support the etiological link between Gram-negative bacterial infection and autoimmune disease. Models proposed to account for the link between infection and autoimmunity include inflammation-induced presentation of cryptic self-epitopes, antigen persistence and molecular mimicry. Several studies support molecular mimicry as a mechanism for the involvement of class II epitopes in infectious disease-induced self-reactivity. Here, we have identified an immunodominant epitope derived from the S. typhimurium GroEL molecule. This epitope is presented by the mouse H2-T23-encoded class Ib molecule Qa-1 and was recognized by CD8+ cytotoxic T lymphocytes induced after natural infection. S. typhimurium-stimulated cytotoxic T lymphocytes recognizing the GroEL epitope cross-reacted with a peptide derived from mouse heat shock protein 60 and recognized stressed macrophages. Our results indicate involvement of MHC class Ib molecules in infection-induced autoimmune recognition and indicate a mechanism for the etiological link between Gram-negative bacterial infection and autoimmunity.
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PMID:Molecular mimicry mediated by MHC class Ib molecules after infection with gram-negative pathogens. 1065 13

A growing body of evidence suggests that T lymphocytes play an important role in initiating and maintaining the inflammatory process characteristic of the human leukocyte antigen (HLA)-B27-associated spondyloarthropathies. T cells seem to be involved in the primary defense reaction against arthritis-triggering gram-negative bacteria at the site of extra-articular infection, in determining the systemic cytokine pattern, in the recirculation process between gut mucosa and the joint, and in mediating secondary autoimmune joint inflammation. The factors involved in disease chronicity (namely in ankylosing spondylitis and psoriatic arthritis) are still unknown. Autoreactive T cells may contribute to this process by recognition of cross-reactive self-epitopes (ie, molecular mimicry between bacterial and self-antigens). Autoreactive T cells may as well be inappropriately upregulated by bacterial superantigens, or by local inflammatory reactions leading to the uncovering of former cryptic self-epitopes. In this paper, we review recent studies on peripheral blood and synovial T cells in patients with reactive arthritis, enteropathic spondyloarthropathy, psoriatic arthritis, and ankylosing spondylitis.
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PMID:T-cell studies in the spondyloarthropathies. 1112 74

The 65-kDa mycobacterial heat shock protein (Bhsp65) has been invoked in the pathogenesis of both adjuvant arthritis (AA) in the Lewis rat (RT.1(l)) and human rheumatoid arthritis. Arthritic Lewis rats in the late phase of AA show diversification of the T cell response to Bhsp65 C-terminal determinants (BCTD), and pretreatment of naive Lewis rats with a mixture of peptides representing these neoepitopes affords protection against AA. However, the fine specificity and physiologic significance of the BCTD-directed T cell repertoire, and the role of homologous self (rat) hsp65 (Rhsp65), if any, in spreading of the T cell response to Bhsp65 have not yet been examined. We observed that T cells primed by peptides comprising BCTD can adoptively transfer protection against AA to the recipient Lewis rats. However, these T cells can be activated by preprocessed (peptide) form of BCTD, but not native Bhsp65, showing that BCTD are cryptic epitopes. The BCTD-reactive T cells can be activated by the naturally generated (dominant) C-terminal epitopes of both exogenous and endogenous Rhsp65 and vice versa. Furthermore, certain individual peptides constituting BCTD and their self homologs can also induce protection against AA. These results support a model for the diversification of T cell response to Bhsp65 during the course of AA involving up-regulation of the display of cryptic BCTD coupled with spontaneous induction of T cell response to the cross-reactive dominant C-terminal epitopes of Rhsp65. The identification of disease-regulating cryptic determinants in Ags implicated in arthritis provides a novel approach for immunotherapy of rheumatoid arthritis.
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PMID:The regulatory C-terminal determinants within mycobacterial heat shock protein 65 are cryptic and cross-reactive with the dominant self homologs: implications for the pathogenesis of autoimmune arthritis. 1521 Jul 73

Matrix metalloproteinases (MMPs) are endopeptidases that contribute to growth, development and wound healing as well as to pathologies such as arthritis and cancer. Until recently, it has been thought that MMPs participate in these processes simply by degrading extracellular matrix (ECM) molecules. However, it is now clear that MMP activity is much more directed and causes the release of cryptic information from the ECM. By precisely cleaving large insoluble ECM components and ECM-associated molecules, MMPs liberate bioactive fragments and growth factors and change ECM architecture, all of which influence cellular behavior. Thus, MMPs have become a focal point for understanding matrix biology.
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PMID:Regulation of matrix biology by matrix metalloproteinases. 1536 7

Proteoglycan (PG) aggrecan, a major macromolecular component of cartilage, is highly immunogenic; it induces arthritis in genetically susceptible BALB/c mice. The present study maps the T-cell epitope repertoire of cartilage PG by identifying a total of 27 distinct T-cell epitopes. An epitope hierarchy, accounting for the different effector functions of PG-specific T cells, and determinant spreading, has been found. T-cell responses to four epitopes were associated with arthritis induction. Some of the T-cell epitopes were full T-cell activators, whereas a number of subdominant and cryptic epitopes proved to be partial activators in vitro, inducing either cytokine secretion or T-cell proliferation, but not both. A few T-cell epitopes of the core protein of cartilage PG were clearly recognized by T cells in PG-immunized arthritic animals, but the corresponding peptides did not induce T-cell responses when injected into naive BALB/c mice; thus these T-cell epitopes were designated as "conditionally immunogenic."
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PMID:T-cell recognition of differentially tolerated epitopes of cartilage proteoglycan aggrecan in arthritis. 1618 73


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