Beta2-microglobulin-deficient mice are resistant to bullous pemphigoid.
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.
Liu
Z
Z
Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 43226, USA. zhiliu@post.its.mew.edu
Roopenian
D C
DC
Zhou
X
X
Christianson
G J
GJ
Diaz
L A
LA
Sedmak
D D
DD
Anderson
C L
CL
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010391:Pemphigoid, Bullous / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D011961:Receptors, Fc / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000201:enzymology; D012871:Skin Diseases / Q000276:immunology; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000502:physiology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D011961:Receptors, Fc; D001613:beta 2-Microglobulin; D009195:Peroxidase