Do tissue levels of autoantigenic aminoacyl-tRNA synthetase predict clinical disease?
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.
Kron
Michael A
MA
Institute of International Health, Colleges of Osteopathic and Human Medicine, B-301 West Fee Hall, Michigan State University, East Lansing, MI 48824, USA. kron@msu.edu
Petridis
Michael
M
Haertlein
Michael
M
Libranda-Ramirez
Bernadette
B
Scaffidi
Linda E
LE
D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism*; D001324:Autoantigens / Q000378:metabolism; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D006801:Humans; D018482:Muscle, Skeletal / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D009928:Organ Specificity; D010179:Pancreas / Q000201:enzymology*; D011379:Prognosis; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D014018:Tissue Distribution
D001324:Autoantigens; D015415:Biomarkers; D000604:Amino Acyl-tRNA Synthetases