MYOSITIS INDUCED BY NAKED DNA IMMUNIZATION WITH THE GENE FOR HISTIDYL-TRANSFER-RNA SYNTHETASE

Polymyositis is regarded as an autoimmune inflammatory muscle disease, A major subgroup of patients have autoantibodies to cellular histidyl -transfer RNA synthetase (HRS), We have analyzed the role of the autoa ntigen HRS in the induction of murine myositis in a comparative study of inoculation of BALB/c mice with recombinant HRS protein versus nake d DNA coding for HRS, Adult BALB/c mice produced antibodies to human H RS following inoculation with HRS protein and adjuvant, but myositis w as not observed, Alternatively, expression plasmid DNA constructs enco ding full-length and truncated human HRS were inoculated intramuscular ly in gene transfer studies, DNA-inoculated mice produced relatively l ow anti-HRS antibody titers, However, in contrast to recombinant HRS p rotein-inoculated mice, HRS gene transfer induced pathology with evide nce of cellular infiltration of perivascular and endomysial regions of the inoculated muscle, Multiple inoculations of a plasmid construct e ncoding a hybrid molecule consisting of HRS and the transferrin recept or cytoplasmic tail induced the highest levels of antibodies and persi sting cellular infiltration. Unlike HRS, expression of influenza virus hemagglutinin (HA) following inoculation of an HA plasmid did not ind uce myositis, Transfer of naked DNA constructs expressing HRS is likel y to provide valuable information on the autoimmune response to this p rotein and its role in the development of myositis.