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.