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

Autoantibodies to three of the aminoacyl-transfer RNA (tRNA) synthetases have been reported (for histidine, threonine, and alanine). Most patients with these autoantibodies have polymyositis, and the majority also have interstitial lung disease. This study examined the question of whether autoantibodies to other aminoacyl-tRNA synthetases occur in the sera of myositis patients. We tested sera from patients with myositis with unidentified anticytoplasmic antibodies that immunoprecipitate tRNA for the ability to inhibit the aminoacyl-tRNA synthetases for the remaining 17 amino acids. Three sera showed strong inhibitory activity for a synthetase. OJ and NJ sera (and IgG) significantly inhibited isoleucyl-tRNA synthetase activity, each with 94% inhibition at the screening dilution, whereas other test sera and controls all inhibited less than 50%. OJ and NJ sera immunoprecipitated identical patterns of tRNA, and identical, complex patterns of high m.w. polypeptides that were consistent with the multienzyme synthetase complex of which isoleucyl-tRNA synthetase is a part. EJ serum (and IgG) significantly inhibited glycyl-tRNA synthetase, and immunoprecipitated a unique pattern of transfer RNA, and a strong predominant protein band of 77 kDa. These data strongly suggest that OJ and NJ have autoantibodies to isoleucyl-tRNA synthetase, and that EJ has antibodies to glycyl-tRNA synthetase. The findings of signs of muscle involvement in all three patients, and severe interstitial lung disease in OJ, strengthens the association of antisynthetases with these conditions.
 ...
PMID:Autoantibodies to aminoacyl-transfer RNA synthetases for isoleucine and glycine. Two additional synthetases are antigenic in myositis. 230 38

We established chronic graft vs host disease (GVHD) in (C57BL/10 x DBA/2)F1 mice with an injection of lymphoid cells from the parental DBA/2 strain. In addition to Abs earlier reported, of the 20 animals studied 13 developed Abs against transfer RNA/protein particles. Ten of the 13 sera immunoprecipitated a similar-sized RNA that co-migrated in PAGE with isoleucine tRNA. In immunoblots against proteins affinity purified using anti-isoleucyl-tRNA synthetase prototype serum, 7 of the 10 sera reacted with a polypeptide of 76 kDa that was similar in size to a protein recognized by a human anti-isoleucyl-tRNA synthetase serum. Three of 10 sera significantly and specifically inhibited isoleucyl-tRNA synthetase enzyme activity and one inhibited lysyl-tRNA synthetase activity. These data suggest that the autoantibodies to tRNA-associated proteins that develop in GVHD mice may react with amino acyl-tRNA synthetases, particularly those belonging to the multienzyme complex. Such autoantibodies are associated with myositis in humans, and these mice showed evidence compatible with myositis that appeared to be a manifestation of their GVHD. No previous example of spontaneous development of antisynthetases in animals has been described. We also demonstrated the presence of Abs against the NOR:90 nucleolar Ag as a new target in chronic GVHD. We conclude that chronic GVHD in mice provides a model for the study of the autoimmune responses that characterize human diseases such as mixed connective tissue disease, scleroderma, SLE, and myositis with a wider autoantibody response than that described so far.
 ...
PMID:Autoantibodies to a transfer RNA-associated protein in a murine model of chronic graft versus host disease. 812 Apr 3

Autoantibodies to five aminoacyl-tRNA synthetases have been reported, and all have been associated with a syndrome of myositis and interstitial lung disease. Four of these synthetases exist free in the cytoplasm, but the fifth, isoleucyl-tRNA synthetase (recognized by anti-OJ autoantibodies), is a component of the multi-enzyme complex containing at least seven synthetases. In an effort to better understand the origins of these antibodies, we examined sera from 11 patients with anti-OJ autoantibodies for evidence of reaction with other components of the complex. All sera showed a characteristic pattern of 10 proteins bands by immunoprecipitation from HeLa cell extract. 10 of 11 sera significantly inhibited isoleucyl-tRNA synthetase enzyme activity. Serum and IgG from four patients also inhibited leucyl-tRNA synthetase activity, and serum and IgG from two inhibited lysyl-tRNA synthetase. Immunoblotting experiments supported reaction of the two sera with lysyl-tRNA synthetase, and revealed additional reactivity of three sera with a 160-kD component believed to be glutaminyl-tRNA synthetase. Despite reaction of some sera with additional synthetases, the immunoprecipitated tRNA appeared the same with all sera, and functioned as tRNA(ile). While reaction with more than one synthetase was seen with some anti-OJ sera, all synthetases targeted by anti-OJ sera were components of the complex, rather than unassociated synthetases. These findings suggest that an initial autoantibody response against isoleucyl-tRNA synthetase was followed by extension to involve other components of the synthetase complex. These observations may have implications for understanding the generation of antisynthetase autoantibodies.
 ...
PMID:Reaction of anti-OJ autoantibodies with components of the multi-enzyme complex of aminoacyl-tRNA synthetases in addition to isoleucyl-tRNA synthetase. 851 67

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.
 ...
PMID:Interstitial lung disease with autoantibodies against aminoacyl-tRNA synthetases in the absence of clinically apparent myositis. 887 Jan 13

Anti-OJ autoantibodies are rare myositis-specific autoantibodies that have been described to target isoleucyl-tRNA synthetase. Routinely used multiplex assays perform poorly in detection of anti-OJ antibodies. In this manuscript, we review the existing literature on critical issues in detection of anti-OJ and the clinical features associated with anti-OJ. The challenging detection with line/blot immunoassays and ELISAs is most likely related to the characteristics of the autoantigen involved, which is part of a multi-enzyme synthetase complex. Anti-OJ autoantibodies might therefore be more aptly termed anti-OJ complex autoantibodies. Anti-OJ autoantibodies are associated with the anti-synthetase syndrome, with interstitial lung disease (ILD) frequently being the sole manifestation. Myositis, present in the majority of patients with anti-OJ antibodies, is more severe than in patients with other anti-aminoacyl-tRNA synthetases. Most patients respond to glucocorticoid therapy. As detection of anti-OJ is relevant for treatment, reliable and practical detection is needed. Meanwhile, clinicians need to be aware of the possibility of anti-OJ in patients with ILD, isolated or in combination with myositis.
 ...
PMID:Anti-OJ autoantibodies: Rare or underdetected? 3105 43