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Zhi Liu^*, Derry C. Roopenian, Xiaoye Zhou^*, Greg J. Christianson, Luis A. Diaz^*, Daniel D. Sedmak^||, and Clark L. Anderson

From the ^* Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 43226; The Jackson Laboratory, Bar Harbor, Maine 04609; and the Department of Internal Medicine and the ^|| Department of Pathology, The Ohio State University, Columbus, Ohio 43210

Recent understanding of the mechanism of immunoglobulin G (IgG) catabolism has yielded new insight into antibody-mediated diseases. We proposed that β₂-microglobulin (β₂m)–deficient mice have been protected from systemic lupus erythematosis (SLE)–like syndromes because they lack the β₂m-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 β₂m-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 β₂m-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 β₂m-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.

¹ Abbreviations used in this paper: β₂m, β₂-microglobulin; BMZ, basement membrane zone; BP, bullous pemphigoid; FcRn, Fc receptor neonatal; IF, immunofluorescence; MPO, myeloperoxidase; SLE, systemic lupus erythematosus.

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