Faculty Research 1990 - 1999

Title

Beta2-microglobulin-deficient mice are resistant to bullous pemphigoid.

Document Type

Article

Publication Date

1997

Keywords

Animal, Autoantibodies: im, Crosses-Genetic, Disease-Models-Animal, Female, IgG: im, me, Immunity-Natural, Lupus-Erythematosus-Systemic: im, Male, Mice, Mice-Inbred-Strains, Pemphigoid-Bullous: im, Peroxidase: me, Rabbits, Receptors-Fc: im, me, Skin: en, Skin-Diseases: im, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S

JAX Source

J Exp Med 1997 Aug 29;186(5):777-83

Grant

R29AI40768/AI/NIAID, RO1AR32599/AR/NIAMS, R37AR32081/AR/NIAMS

Abstract

Recent understanding of the mechanism of immunoglobulin G (IgG) catabolism has yielded new insight into antibody-mediated diseases. We proposed that beta2-microglobulin (beta2m)-deficient mice have been protected from systemic lupus erythematosis (SLE)-like syndromes because they lack the beta2m-associated IgG protection receptor (FcRn) and therefore catabolize IgG, including pathogenic IgG autoantibodies, considerably more rapidly than normal mice. Such an hypothesis would predict that beta2m-deficient mice would also be resistant to experimental bullous pemphigoid, a disease with a pathogenesis thought to be much simpler than SLE, being the result of antibody directed toward a pathogenic epitope on the epidermal hemidesmosome that anchors basal keratinocytes to the basement membrane. To test this hypothesis, we administered pathogenic rabbit antibody directed toward the hemidesmosome to beta2m-deficient mice and to normal control mice, both intraperitoneally and intradermally, and assessed the mice clinically, histologically, and immunologically for manifestations of skin disease. We found that the beta2m-deficient mice were protected when the antibody was given intraperitoneally whereas intradermal administration resulted in blisters only slightly less severe than those seen in normal mice. These data would indicate that autoantibody-mediated inflammation might be prevented or controlled by appropriate modulation of FcRn function.