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)

A group of autoantibodies have been identified that are found almost exclusively in patients with polymyositis and dermatomyositis (myositis-specific antibodies). Most have been associated with characteristic clinical subgroups. Five of the myositis-specific antibodies are directed at aminoacyl-tRNA synthetases and have been associated with a similar clinical syndrome marked by myositis, interstitial lung disease, arthritis, and Raynaud's phenomenon (antisynthetase syndrome). Myositis-specific antibodies can help with patient diagnosis, subgroup classification, and possible prognosis. Their role in the pathogenesis of myositis remains to be defined, but their production is genetically influenced and appears to be linked to fundamental etiologic factors.
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PMID:Autoantibodies in polymyositis. 137 27

The IIM are a heterogeneous group of systemic rheumatic diseases which share the common features of chronic muscle weakness and mononuclear cell infiltrates in muscle. A number of classification schemes have been proposed for them, but none takes into consideration the marked immunologic, clinical, and genetic heterogeneity of the various clinical groups. We compared the usefulness of myositis-specific autoantibodies (anti-aminoacyl-tRNA synthetases, anti-SRP, anti-Mi-2 and anti-MAS) to the standard clinical categories (polymyositis, dermatomyositis, overlap myositis, cancer-associated myositis, and inclusion body myositis) in predicting clinical signs and symptoms, HLA types, and prognosis in 212 adult IIM patients. Although patients with inclusion body myositis (n = 26) differed in having significantly more asymmetric and distal weakness, falling, and atrophy than other patients, there were few other significant differences among the other clinical groups. In contrast, autoantibody status defined distinct sets of patients and each patient had only 1 myositis-specific autoantibody. Patients with anti-amino-acyl-tRNA synthetase autoantibodies (n = 47), compared to those without these antibodies, had significantly more frequent arthritis, fever, interstitial lung disease, and "mechanic's hands"; HLA-DRw52; higher mean prednisone dose at survey, higher proportion of patients receiving cytotoxic drugs, and higher death rates. Those with anti-signal recognition particle antibodies (n = 7) had increased palpitations; myalgias; DR5, DRw52; severe, refractory disease; and higher death rates. Patients with anti-Mi-2 antibodies (n = 10) had increased "V-sign" and "shawl-sign" rashes, and cuticular overgrowth; DR7 and DRw53; and a good response to therapy. The 2 patients with anti-MAS antibodies were the only ones with alcoholic rhabdomyolysis preceding myositis; both had insulin-dependent diabetes mellitus, and both had HLA-B60, -C3, -DR4, and -DRw53. These findings suggest that myositis-specific autoantibody status is a more useful guide than clinical group in assessing patients with myositis, and that specific associations of immunogenetics, immune responses, and clinical manifestations occur in IIM. Thus the myositis-specific autoantibodies aid in interpreting the diverse symptoms and signs of myositis patients and in predicting their clinical course and prognosis. We propose, therefore, that an adjunct classification of the IIM, based on the myositis-specific autoantibody status, be incorporated into future studies of their epidemiology, etiology, and therapy.
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PMID:A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. 165 47

The clinical and laboratory features of 29 patients who had one of three anti-aminoacyl-tRNA synthetase autoantibodies, anti-Jo1 (histidyl-tRNA synthetase), anti-PL12 (alanyl-tRNA synthetase) or anti-PL7 (threonyl-tRNA synthetase) were analysed and compared with the findings of other published reports. These autoantibodies were found to be associated with a syndrome delineated by inflammatory myositis (24 patients) and pulmonary fibrosis (23 of 29), but also including inflammatory arthritis (26/29), keratoconjunctivitis sicca (17/29), sclerodactyly (21/29), Raynaud's phenomenon (27/29), hepatitis (8/29) and subcutaneous calcinosis (7/29). The most important clinical determinant of outcome in this group of patients was the severity of the interstitial pulmonary disease. No patient fulfilled the classification criteria for systemic lupus erythematosus, although 10 had autoantibodies to extractable nuclear antigens including Ro, La, RNP, and Sm, and two patients had anti-dsDNA antibodies. Although it seems unlikely that anti-aminoacyl-tRNA synthetase antibodies are directly responsible for causing disease, they may provide an important clue to the aetiology of this unusual syndrome.
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PMID:Polymyositis, pulmonary fibrosis and autoantibodies to aminoacyl-tRNA synthetase enzymes. 226 80

Caprine arthritis-encephalitis virus (CAEV) and visna virus are pathogenic lentiviruses of goats and sheep which share morphologic features and sequence homology with human T-cell lymphotropic virus type III (HTLV-III), the etiologic agent of the acquired immune deficiency syndrome. The nucleotide sequence of the CAEV long terminal repeat (LTR) was determined, and it was found to be 450 base pairs long, with U3, R, and U5 regions of 287, 85, and 78 base pairs, respectively. Portions of the CAEV LTR are closely homologous to analogous regions of visna virus. The CAEV LTR is not significantly homologous with the HTLV-III LTR; however, like HTLV-III, visna virus, and equine infectious anemia virus, CAEV uses tRNA lysine as a primer for reverse transcription. The transcriptional activity of the CAEV and visna virus LTRs was measured by a chloramphenicol acetyltransferase assay, and the activity of the visna virus LTR was generally higher in a variety of uninfected cell types. Infection of cells with visna virus markedly increased gene expression directed by either the CAEV or visna virus LTR, but in contrast, infection of cells with CAEV had little effect on the activity of either LTR. The lack of trans-activation by CAEV, a virus which causes debilitating arthritis and encephalitis in goats, suggests that trans-activation may not be a general property of pathogenic lentiviruses.
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PMID:Nucleotide sequence and transcriptional activity of the caprine arthritis-encephalitis virus long terminal repeat. 302 73

The nucleotide sequence of the long terminal repeat (LTR) of caprine arthritis encephalitis virus (CAEV), a prototype lentivirus was determined. 6-bp directly repeated host cell sequences flank the 376-bp proviral LTRs. By comparison with other retroviral sequences, the CAEV LTR likely contains U3, R and U5 regions 207, 86 and 83 base-pairs in length, respectively. Sequences conforming to consensus transcriptional promoter sites were identified in the U3 region upstream of a potential transcription initiation site. A consensus polyadenylation signal is present 20 bases upstream of the putative R-U5 border and a potential poly(A) addition site. Sequence comparisons of the CAEV LTR with those of other retroviruses uncovered significant similarities with that of visna virus. No other global homologies with other retrovirus LTRs could be detected. CAEV utilizes a primer binding site complementary to lysine tRNA as does visna, AIDS associated retroviruses, and mouse mammary tumor virus. The putative primer for positive-strand DNA synthesis identified in the CAEV sequence is identical to that of visna virus and very similar to those of AIDS retroviruses and MMTV. In addition, a stretch that includes the TATA box of the CAEV LTR resembles closely the corresponding region in the AIDS retrovirus. These and other findings further strengthen the classification of AIDS retrovirus as a lentivirus.
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PMID:Nucleotide sequence analysis of the long terminal repeat of integrated caprine arthritis encephalitis virus. 376 21

Evidence of autoimmune muscle injury and of systemic autoimmunity is seen in PM and DM. In typical PM, a cell-mediated attack on muscle fibers by CD8+ cytotoxic T cells predominates, directed at an unknown antigen. In DM, vascular injury is prominent, with loss of muscle capillaries and ischemic muscle damage, apparently mediated by local complement activation in small muscle vessels. Although humoral immunity seems more important in the pathogenesis of DM, serum autoantibodies are commonly found in both forms. About one third of patients have MSAs, whereas others have less specific antibodies such as anti-U1RNP, often associated with overlap syndromes involving myositis. MSAs are mutually exclusive and define characteristic clinical subgroups. Antibodies to five of the aminoacyl-tRNA synthetases are each associated with an "antisynthetase syndrome" marked by myositis, ILD, arthritis, and other features, but individual patients have only a single antisynthetase. Rare autoantibodies to certain translation factors may be associated with a similar syndrome. Anti-SRP is commonly associated with severe, acute, resistant myositis, whereas anti-Mi-2, the only MSA directed at a nuclear protein, is specifically associated with DM. Patients with anti-PM-Scl commonly have an overlap syndrome of PM/DM and SSc. Recent studies have recognized other antibodies in PM and DM, including antibody to endothelial cells, heat shock proteins, and, in a high proportion of patients, a 56-kd component of a ribonucleoprotein particle. The MSAs and their antigens are being characterized in detail. To date, data suggest similarity of predominant epitopes between different patients and a tendency toward conformational epitopes. It is not known if the recognized autoantibodies participate in tissue injury or pathogenetic processes, but production of the MSAs appears to be linked to etiologic factors and can be a clue to understanding the disease. Although these autoimmune responses are becoming better defined, the inciting events leading to generation of these responses and development of PM and DM remain unknown.
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PMID:Immune manifestations of inflammatory muscle disease. 785 26

Autoantibodies against aminoacyl-tRNA synthetases (antisynthetases) have been found to be highly specific for polymyositis and dermatomyositis and to correlate strongly with complicating interstitial lung disease (ILD). We describe the clinical presentations and course of 10 patients with ILD and anti-synthetase antibodies in whom underlying myositis was not clinically evident. Anti-PL-12 antibodies (antialanyl-tRNA synthetase) were most common (60%), followed by anti-Jo-1 (antihistidyl-tRNA synthetase) and anti-OJ (anti-isoleucyl-tRNA synthetase) (20% each). All 10 patients had anticytoplasmic antibodies by indirect immunofluorescence on HEp-2 cells. Five of 10 presented with features of connective tissue disease, whereas two presented with acute respiratory failure, two with insidious onset of diminished exercise tolerance, and one with persistent cough. All but one patient received corticosteroids, four were given oral cyclophosphamide, and two azathioprine. ILD resolved or stabilized in five patients (50%), and progressed in four (40%). The "antisynthetase syndrome" may occur in the absence of clinical myositis, and the ILD in these patients is usually responsive to therapy. Antisynthetase testing should be considered in patients with ILD who have a cytoplasmic pattern by antinuclear antibody (ANA) testing on HEp-2 cells, because early recognition and treatment of such patients affects their clinical course.
Semin Arthritis Rheum 1996 Aug
PMID:Interstitial lung disease with autoantibodies against aminoacyl-tRNA synthetases in the absence of clinically apparent myositis. 887 Jan 13

We present two cases of interstitial pneumonia (IP) whose sera contain autoantibodies to PL-12 (alanyl tRNA synthetase). The first patient is a 47-year-old female who was diagnosed as IP and treated with corticosteroid at another hospital. She was admitted to Keio University Hospital due to worsening of dyspnea and polyarthritis. Laboratory studies revealed elevation of LDH and CRP, and her chest radiography showed interstitial fibrosis. Because of clinical deterioration, the dose of corticosteroid was increased (prednisolone 40 mg/day) and her symptom was stabilized. The second patient, a 55 year-old female, was admitted to Tokyo Metropolitan Ohtsuka Hospital because of dyspnea on exertion and polyarthritis. She did not show any symptom of myositis and was diagnosed as IP with arthritis on the basis of her clinical and chest radiography. She was treated with oral corticosteroid (prednisolone 30 mg/day), which resulted in improvement of her respiratory symptom and arthritis. Both patients were found to have autoantibodies to the PL-12. Autoantibodies to aminoacyl tRNA synthetases have been recognized as having a linkage with myositis mainly because of observations of the Jo-1 specificity. There was one report on a North American population that most but not all patients with anti-PL-12 antibodies had myositis. However, the clinical significance of anti-PL-12 has not been examined in Japanese patients. These patients suggested that anti-PL-12 antibodies have a stronger association with IP than myositis in Japanese patients.
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PMID:[Two cases of interstitial pneumonia with anti-PL-12 (alanyl tRNA synthetase) antibodies]. 912 26

Histidyl-tRNA synthetase (HisRS) is responsible for the synthesis of histidyl-transfer RNA, which is essential for the incorporation of histidine into proteins. This amino acid has uniquely moderate basic properties and is an important group in many catalytic functions of enzymes. A compilation of currently known primary structures of HisRS shows that the subunits of these homo-dimeric enzymes consist of 420-550 amino acid residues. This represents a relatively short chain length among aminoacyl-tRNA synthetases (aaRS), whose peptide chain sizes range from about 300 to 1100 amino acid residues. The crystal structures of HisRS from two organisms and their complexes with histidine, histidyl-adenylate and histidinol with ATP have been solved. HisRS from Escherichia coli and Thermus thermophilus are very similar dimeric enzymes consisting of three domains: the N-terminal catalytic domain containing the six-stranded antiparallel beta-sheet and the three motifs characteristic of class II aaRS, a HisRS-specific helical domain inserted between motifs 2 and 3 that may contact the acceptor stem of the tRNA, and a C-terminal alpha/beta domain that may be involved in the recognition of the anticodon stem and loop of tRNA(His). The aminoacylation reaction follows the standard two-step mechanism. HisRS also belongs to the group of aaRS that can rapidly synthesize diadenosine tetraphosphate, a compound that is suspected to be involved in several regulatory mechanisms of cell metabolism. Many analogs of histidine have been tested for their properties as substrates or inhibitors of HisRS, leading to the elucidation of structure-activity relationships concerning configuration, importance of the carboxy and amino group, and the nature of the side chain. HisRS has been found to act as a particularly important antigen in autoimmune diseases such as rheumatic arthritis or myositis. Successful attempts have been made to identify epitopes responsible for the complexation with such auto-antibodies.
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PMID:Histidyl-tRNA synthetase. 1043 27

Autoantibodies directed against specific human aminoacyl-tRNA synthetases have been associated with a clinical picture including myositis, arthritis, interstitial lung disease and other features that has been referred to as the "anti-synthetase syndrome". Anti-asparaginyl-tRNA synthetase autoantibodies (anti-KS), the most recently described anti-synthetase autoantibodies, are directed against human cytosolic asparaginyl-tRNA synthetase and neutralize specifically its activity. Here we show that these antibodies recognize two epitopes on the human enzyme, an N-terminal epitope reactive in immunoblot experiments and a heat-labile epitope in the catalytic domain. In contrast to the well studied anti-Jo-1 autoantibodies anti-KS when bound to the synthetase increase the affinity of the synthetase for its tRNA substrate and prevent aminoacylation without interfering with the amino acid activation step.
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PMID:Human anti-asparaginyl-tRNA synthetase autoantibodies (anti-KS) increase the affinity of the enzyme for its tRNA substrate. 1131 Dec 35


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