MECHANISMS OF ACANTHOLYSIS IN PEMPHIGUS-VULGARIS - ROLE OF IGG VALENCE

Pemphigus vulgaris (PV) is a dermatosis mediated by autoantibodies aga inst desmoglein 3 (Dsg3), It was known that intraperitoneal tip) injec tions of PV IgG and PV F(ab')(2), but not of PV Fab, into neonatal mic e reproduced the key features of the disease in these animals, It was proposed that crosslinking of antigen by bivalent PV autoantibodies ma y trigger acantholysis in PV, In the present study, we have used subcu taneous (sc) injections of PV IgG and its proteolytic fragments into n eonatal mice to test equimolar amounts of these autoantibody fractions . Mice developed clinical and histological features of PV in a dose de pendent manner following a similar time course. PV IgG and Fab fractio ns induced acantholysis as early as 2 hr after the injection. It was a lso demonstrated that sc injections of PV Fab were more effective in i nducing disease than ip injections. PV autoantibodies may bind an ''ad hesive site'' of Dsg3 and impair its function, thus triggering acantho lysis. (C) 1997 Academic Press.