Do tissue levels of autoantigenic aminoacyl-tRNA synthetase predict clinical disease?

Michigan State University, Ист-Лансинг, Michigan, United States
Medical Hypotheses (Impact Factor: 1.07). 02/2005; 65(6):1124-7. DOI: 10.1016/j.mehy.2005.06.016
Source: PubMed


The etiologies of most autoimmune diseases are not completely understood. Aminoacyl-tRNA synthetases (AARS) are a family of heterogenous enzymes responsible for protein synthesis and whose secondary functions include a role in autoimmune myositis. A subset of patients with idiopathic inflammatory myopathies demonstrate autoantibody against specific cytoplasmic AARS and the human asparaginyl-tRNA synthetase (AsnRS) has been shown to be a potent chemokine that interacts with CCR3 chemokine receptors. One way in which a chemotactic cytoplasmic enzyme might contribute to tissue inflammation is if it were abundant in a specific injured tissue and thereby released to the microenvironment at times of cellular damage. To test this hypothesis, the relative levels of AsnRS mRNA were studied in six human tissues. A 1.6 kbF RNA probe identified highly variable levels of the corresponding mRNA in Northern blot analysis of human lung, brain, heart, skeletal muscle, pancreas and liver. The highest levels of signal were noted in muscle and pancreas. Polyclonal antibody raised against recombinant human AsnRS identified abundant antigenic material in the pancreas, in particular in islet cells. Thus, the local abundance of an endogenous pro-inflammatory autoantigen may provide one explanation for perpetuation or exacerbation of tissue specific immune-mediated pathologies.

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    • "Recent reports have shown that expression of some aaRSs can be found specifically in the pancreas (Antonellis et al. 2003, Kron et al. 2005). However, suborganellar localization of aaRSs within the pancreas has not been confirmed. "
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    • "Within a class, each AARS exhibits three highly conserved motifs distributed within a poorly conserved amino-terminal domain and a more highly conserved carboxy-terminal region (Weiner 1999; Ibba et al. 2000). Human cytoplasmic AsnRS is a class II AARS expressed in many human tissues, particularly in the pancreas, skeletal, and cardiac muscle (Kron et al. 2005). A wide range of secondary functions of AARS have been documented in various species, including roles in transcriptional regulation, mitochondrial RNA splicing, control of cell growth, and cytokine-or chemokine-like activity (Martinis et al. 1999). "
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