Rabbits immunized with a peptide encoded for by the 230-kD bullous pemphigoid antigen cDNA develop an enhanced inflammatory response to UVB irradiation: a potential animal model for bullous pemphigoid.
Previous attempts to develop an animal model of bullous pemphigoid (BP) have failed to result in inflammatory disease in the skin. P1-2 is an 18-amino acid peptide encoded for by the 230-kD BP antigen cDNA that has been shown to contain an epitope recognized by circulating antibodies from patients with BP. The purpose of this study was to determine if ultraviolet B irradiation of rabbits after immunization with the P1-2 peptide would result in an enhanced inflammatory response in the skin to that injury. Three rabbits were immunized with either P1-2 or a control peptide. All rabbits immunized with P1-2, and none of the control rabbits, developed antibodies against P1-2 that bound in vitro to both human and rabbit skin in a linear pattern at the basement membrane zone. Immunized rabbits were irradiated on the flank with ultraviolet light. Rabbits immunized with P1-2 developed an enhanced inflammatory reaction to ultraviolet B irradiation leading to epidermal necrosis and sloughing of some sites in 6-9 d. Control rabbits showed only mild erythema without sloughing, which healed in 4-6 d. Histology in the P1-2 immunized rabbits at 24 h revealed an inflammatory infiltrate of neutrophils at the dermal-epidermal junction, whereas control rabbits showed only mild edema and a sparse inflammatory infiltrate. All the rabbits immunized with P1-2 had linear deposits of immunoglobulin G and C3 at the basement membrane zone of healed skin compared to none of the controls. These findings demonstrate that antibodies against a synthetic peptide encoded by the BP antigen 1 sequence can lead to an enhanced inflammatory response after epithelial injury in rabbit skin.
Hall
R P
RP
Department of Medicine, Duke University School of Medicine, Durham VA Hospital, North Carolina.
Murray
J C
JC
McCord
M M
MM
Rico
M J
MJ
Streilein
R D
RD
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D000071821:Dystonin; D005260:Female; D005455:Fluorescent Antibody Technique; D007114:Immunization; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010391:Pemphigoid, Bullous / Q000276:immunology* / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D011833:Radiation Injuries, Experimental / Q000276:immunology; D012867:Skin / Q000473:pathology / Q000528:radiation effects; D014466:Ultraviolet Rays; D000097805:Collagen Type XVII
D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D004247:DNA; D000071821:Dystonin; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010455:Peptides; D000097805:Collagen Type XVII; C486268:DST protein, human