Pemphigoid Antibody Mediated Attachment of Peripheral Blood Leukocytes at the Dermal-Epidermal Junction of Human Skin

Walter R. Gammon, Daniel M. Lewis, Jaime R. Carlo, Wiley M. Sams, Clayton E. Wheeler
1980 Journal of Investigative Dermatology  
It has b een proposed that cutaneous inflammation and blister formation in bullous pemphigoid is caused by antibodies to the cutaneous basement membrane zone which activate 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 le ukocyte activity in skin. This s tudy describes the in vitro attachment of human peripheral blood leukocytes to the
more » ... mal junction of cryostat skin se. ctions treated with 9/13 pemphigoid sera containing antibodies to the cutaneous b asement membrane zone. A requirement for complement in the reaction was supported by the findings that only complement-fixing p emphigoid 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 r equirement for antibody was supported by the observation that IgG fractions of 4 pemphigoid sera were as effective as whole sera in m ediating le ukocyte attachment. The le ukocyte response was shown to be specific for complement-fixing pemphigoid sera since it was not observed with noncomplementfixing 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 d emonstrates that complement-fixing antibasement membrane zone antibodies may be important in initiating the cellular inflammatory events observed near the d ermal-epidermaljunction in vivo. Bullous pemphigoid is a chronic acquired skin disease characterized clinically by tense blisters and bullae which develop on normal, erythematous, or urticarial skin a nd histologically by dermal-epidermal separation associated with variable degrees of dermal inflammation [1] . While the cause of pemphigoid is unknown, a number of observations suggest that infla mmatory cells are important in pathogenesis and support the concept that leukocyte activity contributes to separation of th e dermal-epidermal junction. Histologic studies show a progressive accumulation of leukocytes in the upper dermis a nd junctional zone prior to blister formation and degranulation of Manuscript
doi:10.1111/1523-1747.ep12531082 pmid:7000926 fatcat:phmmbhnjhjatxoketedn7qyaju