Pemphigoid antibody mediated attachment of peripheral blood leukocytes at the dermal-epidermal junction of human skin.
It has been proposed that cutaneous inflammation and blister formation in bullous pemphigoid is caused by antibodies to the cutaneous basement membrane zone which active complement, thereby, attracting leukocytes to the dermal-epidermal junction. There is, however, no functional evidence which supports a role for pemphigoid antibodies in complement activation or leukocyte activity in skin. This study describes the in vitro attachment of human peripheral blood leukocytes to the dermal-epidermal junction of cryostat skin sections treated with 9/13 pemphigoid sera containing antibodies to the cutaneous basement membrane zone. A requirement for complement in the reaction was supported by the findings that only complement-fixing pemphigoid sera mediated the leukocyte response, a strong correlation existed between complement-fixation titers and leukocyte attachment titers and only leukocytes suspended in fresh serum but not buffer or heat inactivated serum attached at the junction. A requirement for antibody was supported by the observation that IgG fractions of 4 pemphigoid sera were as effective as whole sera in mediating leukocyte attachment. The leukocyte response was shown to be specific for complement-fixing pemphigoid sera since it was not observed with noncomplement-fixing sera or sera from 15 normal human and 22 nonpemphigoid disease controls. This study offers functional evidence for an interaction between pemphigoid antibody, complement and leukocytes in the immunopathogenesis of bullous pemphigoid and demonstrates that complement-fixing antibasement membrane zone antibodies may be important in initiating the cellular inflammatory events observed near the dermal-epidermal junction in vivo.
D000328:Adult; D000937:Antigen-Antibody Reactions; D001485:Basement Membrane / Q000276:immunology; D003168:Complement Fixation Tests; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007231:Infant, Newborn; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D010391:Pemphigoid, Bullous / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000276:immunology* / Q000473:pathology; D012872:Skin Diseases, Vesiculobullous / Q000276:immunology*
D007074:Immunoglobulin G