| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
In the previous year, we have reported that autoimmune MRL/lpr mice, rendered genetically deficient for nucleobindin (Nuc), which is known to augment anti-DNA antibody production, developed periarteritis nodosa (PN)-like ANCA-positive necrotizing vasculitis accompanying crescentic glomerulonephritis (CrGN) at high frequency. The characteristic was that the Nuc-deficient MRL/lpr mice(-/-) produced immune complexes (IC) in the serum 3 times as much as those in wild MRL/lpr mice (+/+). Thus, we analyzed the components of IC in kidneys of the -/- mice by SDS-PAGE under native conditions. A major band at 45 kd region on the gel, which was electrophoretically transferred onto a PVDF membrane, was processed for aminoacid sequencing. It turned out to be arginino-succinate synthase (ASS), and was further confirmed by 2-dimensional electrophoresis. IC also contained actin to some extent as shown in the previous meeting. The content of ASS was 10 times as much as that of actin, as far as judged from staining intensity. Accordingly, we produced recombinant mouse ASS for ELISA.As was expected, the level of anti-ASS antibodies in the -/- mice was significantly higher than those of the +/+ mice. Of note was that the level was associated well with the presence of early lesions comparable to the stage from I to II of human classical PN but not with the severity of vasculitis (stage III and IV) and/or GN.A novel antigen-antibody system revealed in this experiment using animal model for PN or microscopic polyangiitis (MPA) will be of use for an early prediction of Pie fatal disease such as MPA in humans.
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