Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027121 (myositis)
 4,538 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The presence of autoantibodies to the Ro52 protein in sera from patients with idiopathic inflammatory myopathies has recently been reported. These antibodies were found predominately in sera with the myositis-specific autoantibody anti-histidyl-tRNA synthetase (anti-Jo-1). In this report, we analysed sera from 216 patients to determine whether anti-Ro52 antibodies are associated with myositis autoantibodies other than anti-Jo-1. These included sera containing antibodies that recognize threonyl- or alanyl-tRNA synthetases, Mi-2, PM-Scl, signal recognition particle (SRP), as well as the systemic sclerosis-related antibodies anti-topoisomerase I (Scl-70) and anti-centromere. A high proportion of sera that contain anti-aminoacyl-tRNA synthetase antibodies, anti-SRP, or anti-PM-Scl antibodies were found to contain antibodies to the Ro52 protein. In contrast, in sera containing anti-Mi-2, anti-Scl-70 or anti-centromere antibodies, anti-Ro52 antibodies were absent or occurred infrequently. In addition, only one serum from 41 rheumatoid arthritis patients was positive for anti-Ro52 autoantibodies. These data indicate that anti-Ro52 antibodies are produced in particular subsets of myositis patients, and are not limited to sera with anti-Jo-1 antibodies.
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PMID:The association of anti-Ro52 autoantibodies with myositis and scleroderma autoantibodies. 1004 34

Autoantibodies to histidyl-tRNA synthetase (HisRS) or to alanyl-, asparaginyl-, glycyl-, isoleucyl-, or threonyl-tRNA synthetase occur in approximately 25% of patients with polymyositis or dermatomyositis. We tested the ability of several aminoacyl-tRNA synthetases to induce leukocyte migration. HisRS induced CD4(+) and CD8(+) lymphocytes, interleukin (IL)-2-activated monocytes, and immature dendritic cells (iDCs) to migrate, but not neutrophils, mature DCs, or unstimulated monocytes. An NH(2)-terminal domain, 1-48 HisRS, was chemotactic for lymphocytes and activated monocytes, whereas a deletion mutant, HisRS-M, was inactive. HisRS selectively activated CC chemokine receptor (CCR)5-transfected HEK-293 cells, inducing migration by interacting with extracellular domain three. Furthermore, monoclonal anti-CCR5 blocked HisRS-induced chemotaxis and conversely, HisRS blocked anti-CCR5 binding. Asparaginyl-tRNA synthetase induced migration of lymphocytes, activated monocytes, iDCs, and CCR3-transfected HEK-293 cells. Seryl-tRNA synthetase induced migration of CCR3-transfected cells but not iDCs. Nonautoantigenic aspartyl-tRNA and lysyl-tRNA synthetases were not chemotactic. Thus, autoantigenic aminoacyl-tRNA synthetases, perhaps liberated from damaged muscle cells, may perpetuate the development of myositis by recruiting mononuclear cells that induce innate and adaptive immune responses. Therefore, the selection of a self-molecule as a target for an autoantibody response may be a consequence of the proinflammatory properties of the molecule itself.
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PMID:Histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, autoantigens in myositis, activate chemokine receptors on T lymphocytes and immature dendritic cells. 1223 11

Autoantibodies are a hallmark in the diagnosis of many systemic autoimmune rheumatic diseases (SARD) including idiopathic inflammatory myopathies (IIM). Based on their specificity, autoantibodies in IIM are grouped into myositis specific (MSA) and myositis associated autoantibodies (MAA). Among the MSA, autoantibodies against aminoacyl-tRNA synthetases (ARS) represent the most common antibodies and can be detected in 25-35% of patients. The presence of ARS and other autoantibodies has become a key feature for classification and diagnosis of IIM and is increasingly used to define clinically distinguishable IIM subsets. For example, anti-ARS autoantibodies are the key features of what has become known as anti-synthetase syndrome (aSS), characterized by multiple organ involvement, primarily interstitial lung disease, often accompanied by myositis, non-erosive arthritis, Raynaud's phenomenon, fever, and "mechanic's hands". Autoantibodies directed to eight different ARS have been described: Jo-1 (histidyl), PL-7 (threonyl), PL-12 (alanyl), OJ (isoleucyl), EJ (glycyl), KS (asparaginyl), Zo (phenylalanyl) and Ha (tyrosyl). Each anti-ARS antibody seems to define a distinctive clinical phenotype. Although several research methods and commercial tests are available, routine testing for anti-ARS autoantibodies (other than anti-Jo-1/histidyl-tRNA synthetase) is not widely available, sometimes leading to delays in diagnosis and poor disease outcomes.
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PMID:Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review. 2442 90

Antisynthetase syndrome (ASS) is a rare chronic autoimmune disorder (2-3 times more common in women than in men), associated with interstitial lung disease (the most important feature), dermatomyositis (DM), and polymyositis (PM). The cause of ASS is unknown. Recent developments in immunology have improved our knowledge and it is now possible to classify ASS according to the presence of myositis specific autoantibodies. The hallmark of ASS is the presence of serum autoantibodies directed against aminoacyl-tRNA synthetases (anti-ARS involved in protein synthesis). ASS is due to IgG antibodies directed against the enzyme synthase. Antisynthetase antibodies (ASAb) include: anti-histidyl- (anti-Jo-1, being the best known), anti-threonyl- (anti-PL-7), anti-alanyl (anti-PL-12), anti-isoleucyl- (anti-OJ), anti-glycyl- (anti-EJ), anti-asparaginyl- (anti-KS), anti-Wa, anti-tyrosil- (anti-YRS), anti-phenylalanyl-transfer RNA synthetase (anti-Zo), and anti-signal recognition particle (anti-SRP). Anti-Jo-1 is the most common ASAb (in ~20-30% of PM/DM patients).
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PMID:New Insights into Antisynthetase Syndrome. 2846 32

Incorporation of d-amino acids into peptidoglycan is a unique metabolic feature of bacteria. Since d-amino acids are not metabolic substrates in most mammalian tissues, this difference can be exploited to detect living bacteria in vivo. Given the prevalence of d-alanine in peptidoglycan muropeptides, as well as its role in several antibiotic mechanisms, we targeted this amino acid for positron emission tomography (PET) radiotracer development. d-[3-11C]Alanine and the dipeptide d-[3-11C]alanyl-d-alanine were synthesized via asymmetric alkylation of glycine-derived Schiff-base precursors with [11C]methyl iodide in the presence of a cinchonidinium phase-transfer catalyst. In cell experiments, both tracers showed accumulation by a wide variety of both Gram-positive and Gram-negative pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. In a mouse model of acute bacterial myositis, d-[3-11C]alanine was accumulated by living microorganisms but was not taken up in areas of sterile inflammation. When compared to existing clinical nuclear imaging tools, specifically 2-deoxy-2-[18F]fluoro-d-glucose and a gallium citrate radiotracer, d-alanine showed more bacteria-specific uptake. Decreased d-[3-11C]alanine uptake was also observed in antibiotic-sensitive microbes after antimicrobial therapy, when compared to that in resistant organisms. Finally, prominent uptake of d-[3-11C]alanine uptake was seen in rodent models of discitis-osteomyelitis and P. aeruginosa pneumonia. These data provide strong justification for clinical translation of d-[3-11C]alanine to address a number of important human infections.
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PMID:Sensing Living Bacteria in Vivo Using d-Alanine-Derived 11C Radiotracers. 3212 33

We report a rare case of antisynthase syndrome (ASS) complicated with Kaposi sarcoma, analyze its clinical characteristics, and review the literature on the topic. An 80-year-old male patient developed fever, cough, and shortness of breath. Lung high-resolution computed tomography showed nonspecific interstitial pneumonia in both lungs, and myositis antibody examination showed strongly positive anti-alanyl tRNA synthase (PL-12) antibodies. Based on these findings, the patient was diagnosed with ASS. After full-dose glucocorticoid treatment, the symptoms of fever and cough were relieved, but skin thickening and pigmentation in both feet were observed. We confirmed Kaposi sarcoma through skin pathology and immunohistochemical examination of the bottom of the patient's feet, and the patient was transferred to a cancer hospital for radiotherapy. ASS presents with some skin changes that might lead to misdiagnosis. ASS complicated with Kaposi sarcoma is rare, and to our knowledge, this is the first case reported in China.
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PMID:Anti-alanyl tRNA positive antisynthase syndrome with Kaposi sarcoma. 3248 20