Antisynthetase syndrome: A distinct disease spectrum

2020 ◽  
Vol 5 (3) ◽  
pp. 178-191
Author(s):  
Kun Huang ◽  
Rohit Aggarwal
Keyword(s):  
Clinical Characteristics ◽  
Trna Synthetase ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Antisynthetase Syndrome ◽  
Aminoacyl Trna Synthetase ◽  
Trna Synthetases ◽  
Disease Spectrum ◽  
Aminoacyl Trna Synthetases ◽  
Distinct Disease

The discovery of novel autoantibodies related to idiopathic inflammatory myopathies (collectively referred to as myositis) has not only advanced our understanding of the clinical, serological, and pathological correlation in the disease spectrum but also played a role in guiding management and prognosis. One group of the myositis-specific autoantibodies is anti-aminoacyl-tRNA synthetase (anti-ARS or anti-synthetase) which defines a syndrome with predominant interstitial lung disease, arthritis, and myositis. Autoantibodies to eight aminoacyl-tRNA synthetases have been identified with anti-Jo1 the most common in all of idiopathic inflammatory myopathies. Disease presentation and prognosis vary depending on which anti-aminoacyl-tRNA synthetase antibody is present. In this review, we will discuss the clinical characteristics, overlap features with other autoimmune diseases, prognostic factors, and management of the antisynthetase syndrome.

scholarly journals Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum Time Course

2019 ◽  
Vol 8 (11) ◽  
pp. 2013 ◽  
Author(s):  
Cavagna ◽  
Trallero-Araguás ◽  
Meloni ◽  
Cavazzana ◽  
Rojas-Serrano ◽  
...  
Keyword(s):  
Time Course ◽  
Clinical Presentation ◽  
Reference Group ◽  
Trna Synthetase ◽  
Antisynthetase Syndrome ◽  
Aminoacyl Trna Synthetase ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Antisynthetase Antibodies ◽  
Clinical Triad

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group’s cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The “ex-novo” occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies’ positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition.

scholarly journals The Evolutionary Fate of Mitochondrial Aminoacyl-tRNA Synthetases in Amitochondrial Organisms

2021 ◽  
Author(s):  
Gabor L. Igloi
Keyword(s):  
Protein Sequence ◽  
Identity Element ◽  
Mitochondrial Gene ◽  
Trna Synthetase ◽  
Aminoacyl Trna Synthetase ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Cognate Trna ◽  
Evolutionary Fate ◽  
Endosymbiotic Evolution

AbstractDuring the endosymbiotic evolution of mitochondria, the genes for aminoacyl-tRNA synthetases were transferred to the ancestral nucleus. A further reduction of mitochondrial function resulted in mitochondrion-related organisms (MRO) with a loss of the organelle genome. The fate of the now redundant ancestral mitochondrial aminoacyl-tRNA synthetase genes is uncertain. The derived protein sequence for arginyl-tRNA synthetase from thirty mitosomal organisms have been classified as originating from the ancestral nuclear or mitochondrial gene and compared to the identity element at position 20 of the cognate tRNA that distinguishes the two enzyme forms. The evolutionary choice between loss and retention of the ancestral mitochondrial gene for arginyl-tRNA synthetase reflects the coevolution of arginyl-tRNA synthetase and tRNA identity elements.

scholarly journals Natural Trojan horse inhibitors of aminoacyl-tRNA synthetases

2021 ◽  
Author(s):  
Dmitrii Y. Travin ◽  
Konstantin Severinov ◽  
Svetlana Dubiley
Keyword(s):  
Trna Synthetase ◽  
Trojan Horse ◽  
Aminoacyl Trna Synthetase ◽  
Trna Synthetases ◽  
Modes Of Action ◽  
Aminoacyl Trna Synthetases

The structures, biosynthesis, and modes of action of albomycin, microcin C and agrocin 84, antibiotics targeting aminoacyl-tRNA synthetases, are reviewed. Using bioinformatics several new putative aminoacyl-tRNA synthetase inhibitors are predicted.

scholarly journals A Novel Aminoacyl-tRNA Synthetase Appended Domain Can Supply the Core Synthetase with Its Amino Acid Substrate

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1320
Author(s):  
Marc Muraski ◽  
Emil Nilsson ◽  
Benjamin Weekley ◽  
Sandhya Bharti Sharma ◽  
Rebecca W. Alexander
Keyword(s):  
Trna Synthetase ◽  
Mycoplasma Species ◽  
Intracellular Pathogen ◽  
Aminoacyl Trna Synthetase ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Acid Analog ◽  
Methionyl Trna Synthetase ◽  
Acid Substrate ◽  
Amino Acid Substrate

The structural organization and functionality of aminoacyl-tRNA synthetases have been expanded through polypeptide additions to their core aminoacylation domain. We have identified a novel domain appended to the methionyl-tRNA synthetase (MetRS) of the intracellular pathogen Mycoplasma penetrans. Sequence analysis of this N-terminal region suggests the appended domain is an aminotransferase, which we demonstrate here. The aminotransferase domain of MpMetRS is capable of generating methionine from its α-keto acid analog, 2-keto-4-methylthiobutyrate (KMTB). The methionine thus produced can be subsequently attached to cognate tRNAMet in the MpMetRS aminoacylation domain. Genomic erosion in the Mycoplasma species has impaired many canonical biosynthetic pathways, causing them to rely on their host for numerous metabolites. It is still unclear if this bifunctional MetRS is a key part of pathogen life cycle or is a neutral consequence of the reductive evolution experienced by Mycoplasma species.

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