The pathogenesis of autoimmunity in New Zealand mice, I. Induction of antinucleic acid antibodies by polyinosinic-polycytidylic acid

Abstract

Antibodies to DNA and RNA were induced in young NZB/NZW F(1) (B/W) female mice following multiple injections of the interferon-inducer polyinosinic.polycytidylic acid (poly I.poly C). Despite serum concentrations of interferon adequate to inhibit the C-type murine leukemia viruses, there was an acceleration of the autoimmune disease in these animals. Anti-RNA, but not anti-DNA antibodies, were induced in B/W male mice, as well as in NZB and NZW mice. Anti-RNA antibodies were also found in 50 per cent of female B/W mice who had never received poly I.poly C and in 8 of 24 sera from patients with systemic lupus erythematosus. These results suggest that double-stranded RNA functions as a potent antigen in New Zealand mice. Naturally occurring nucleic acids (e.g., viruses) probably act as stimuli to a genetically hyperreactive immune system. According to this hypothesis, the unusual feature in this disease is not a unique virus, but rather the unique genetic susceptibility of the B/W (particularly female) host to immunization with nucleic acids. A similar pathogenetic mechanism may be operative in some humans with systemic lupus erythematosus.