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Do tissue levels of autoantigenic aminoacyl-tRNA synthetase predict clinical disease? Med Hypotheses 2005;65(6):1124-7

Date

08/09/2005

Pubmed ID

16085368

DOI

10.1016/j.mehy.2005.06.016

Abstract

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.

Author List

Kron MA, Petridis M, Haertlein M, Libranda-Ramirez B, Scaffidi LE

Author

Michael Kron MD Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acyl-tRNA Synthetases
Autoantigens
Autoimmune Diseases
Biomarkers
Humans
Muscle, Skeletal
Myocardium
Organ Specificity
Pancreas
Prognosis
Risk Assessment
Risk Factors
Tissue Distribution
jenkins-FCD Prod-388 89e904233d719332173309c68ab82b0b2a78a3a7