BETA(2)-MICROGLOBULIN-DEFICIENT MICE ARE RESISTANT TO BULLOUS PEMPHIGOID

Recent understanding of the mechanism of immunoglobulin G (IgG) catabo lism has yielded new insight into antibody-mediated diseases. We propo sed that beta(2)-microglobulin (beta(2)m)-deficient mice have been pro tected from systemic lupus erythematosis (SLE)-like syndromes because they lack the beta(2)m-associated IgG protection receptor (FcRn) and t herefore catabolize IgG, including pathogenic IgG autoantibodies, cons iderably more rapidly than normal mice. Such an hypothesis would predi ct that beta(2)m-deficient mice would also be resistant to experimenta l bullous pemphigoid, a disease with a pathogenesis thought to be much simpler than SLE, being the result of antibody directed toward a path ogenic epitope on the epidermal hemidesmosome that anchors basal kerat inocytes to the basement membrane. To test this hypothesis, we adminis tered pathogenic rabbit antibody directed toward the hemidesmosome to beta(2)m-deficient mice and to normal control mice, both intraperitone ally and intradermally, and assessed the mice clinically, histological ly, and immunologically for manifestations of skin disease. We found t hat the beta(2)m-deficient mice were protected when the antibody was g iven intraperitoneally whereas intradermal administration resulted in blisters only slightly less severe than those seen in normal mice. The se data would indicate that autoantibody-mediated inflammation might b e prevented or controlled by appropriate modulation of FcRn function.