Autoantibodies to Aminoacyl-tRNA Synthetases

Aminoacyl-tRNA Synthetases in Idiopathic Inflammatory Myopathies: An Update on Immunopathogenic Significance, Clinical and Therapeutic Implications

“…The anti-non-Jo-1 subtypes refer to us as anti-PL-7, anti-PL-12, anti-OJ, anti-EJ, anti-KS, anti-Zo and anti-YRS or anti-Ha antibodies (Hirakata, 2005;Mimori et al, 2007;Solomon et al, 2011). Several characteristics of these anti-ARSs autoantibodies have been emphasized Hirakata, 2005;Solomon et al, 2011;Targoff, 2008):  they focus on functionally related protein enzymes (synthetases) implicated in normal vital cellular cycle, specifically targeting muscle and lung tissue;  they are highly selective, each autoantibody being directed to only one synthetase;  they are mutually exclusive in a given patient, with a few exception only a single antisynthetase being typically found;  they are generally associated with particular phenotypes, a characteristic clinical syndrome being known as "anti-synthetase syndrome", although distinct profiles are defined for each autoantibody; and  they are associated with particular genotypes. Even thought to represent only disease biomarkers, it seems that anti-synthetase autoantibodies are active players in the immunopathogenesis of polymyositis and dermatomyositis.…”

“…Several fascinating paradigms have been effectively anticipated to explain why and how certain intracellular proteins, widely originating in all cellular types, are selectively and specifically targeted in IIMs ). Anti-ARS autoantibodies are associated with anti-synthetase syndrome (ASS), classically defined by several characteristic clinical features including myositis, interstitial lung disease (ILD), arthritis, fever, Raynaud's phenomenon and "mechanic's hands", in addition to other typical skin lesions such as Gottron's papules and heliotrope rash (Betteridge et al, 2007;Betteridge et al, 2009;Gunawardena et al, 2009;Hirakata, 2005). Moreover, distinct associations between certain anti-synthetases profile and corresponding clinical pattern have actually been up-dated.…”

“…Although the exact sequence of events still remains under debate, several pathways are actually proposed including (i) enhanced expression of aminoacyl synthetases in different target tissues, particularly in muscle and lung, (ii) potential role of proteolytic cleavage fragments of aminoacyl-tRNA synthetases generated during inflammation and apoptosis in lesional tissues (muscle and lung), and (iii) autoantigen signaling through chemokine receptors with subsequent amplification of the inflammatory and autoimmune response (Hirakata, 2005). A detailed insight into the ethiopathogenic mechanisms of myostis, along with genetic susceptibility and adjuvant environmental triggers will be further discussed in this section.…”

“…While several subsets of myositis-specific autoantibodies targeting both classic (aminoacyltRNA synthetases, ARSs, signal recognition particle, SRP, and Mi-2) and newly identified (MJ, PMS1, CADM140, p-155/p-140, SAE) autoantigens have been fully described in polymyositis and dermatomyositis Hengstman et al, 2004;Suber et al, 2008), the most widespread group of myositis-specific autoantibodies is represented by anti-aminoacyltRNA synthetase autoantibodies (Gunawardena et al, 2008;Gunawardena et al, 2009). Advancing knowledge in the field of synthetases, either antigenic or non-antigenic subtypes, has been reflected in critical association between genotype, serotype, clinical phenotype and www.intechopen.com (Hirakata, 2005;Mimori et al, 2007), perhaps directly related to their accessibility and expression on the cell surface (Hirakata, 2005).…”

Monoclonal Antibodies Against Tyrosyl-tRNA Synthetase and Its Isolated Cytokine-Like Domain

“…The autoantibodies directed against ARSs have been associated with a clinical picture, including myositis, arthritis, interstinal pneumonia, systemic lupus erythematosus, and other features that have been referred to as the ''anti-synthetase syndrome.'' (12) These diverse connections of ARSs with various human diseases make them attractive targets for the development of therapeutics, although as therapeutic agents of themselves, and as targets for drugs, tRNA synthetases will yield many opportunities for disease intervention. (13) Human tyrosyl-tRNA synthetase (TyrRS) is inactive as a cell-signaling molecule, but it can be split into two distinct cytokines under apoptotic conditions.…”