title: High-molecular-weight kininogen is cleaved in active erythema multiforme.
abstract: Erythema multiforme (EM) is an inflammatory disorder of the skin, which may include mucous membrane involvement, that features target (iris) lesions. Mediators specifically involved in EM are not well characterized; its pathogenesis remains enigmatic. In this study, evidence for participation of kinins in the pathophysiology of inflammation in EM was investigated by assessing cleavage of high-molecular-weight kininogen (HMWK) in plasma. These data were compared with analyses of plasmas from patients with serum sickness, chronic idiopathic urticaria/angioedema, and from normal control subjects. Patients with EM demonstrated significant levels of circulating cleaved HMWK in plasma during active disease (p less than 0.01), which declined during remission/recovery. Plasmas from patients with EM obtained during active disease also demonstrated significant levels of 94 kd C1 inhibitor (p less than 0.01) and C1 inhibitor-kallikrein complexes. Patients with serum sickness and chronic idiopathic urticaria/angioedema did not demonstrate these findings and did not differ from normal control subjects (p = not significant). Although the kininogenase responsible for HMWK cleavage in EM has not been conclusively demonstrated, these findings suggest that HMWK cleavage resulted from activation of the contact system and that some of the manifestations of EM in selected patients may in part be accounted for by inflammatory and proinflammatory actions of kinins. Based on these preliminary findings, it will be important to establish whether or not HMWK cleavage in EM is a general finding in patients with this disorder. Further investigation is needed to characterize more clearly kininogenase activity and elucidate the possible role of kinin generation in EM.
authors.affiliation: Division of Allergy, Scripps Clinic, La Jolla, Calif.
authors.forename: D M
authors.initials: DM
authors.lastname: Lang
authors.forename: S L
authors.initials: SL
authors.lastname: Sugimoto
authors.forename: J G
authors.initials: JG
authors.lastname: Curd
authors.forename: S C
authors.initials: SC
authors.lastname: Christiansen
authors.forename: B L
authors.initials: BL
authors.lastname: Zuraw
mesh_terms: D000328:Adult; D000368:Aged; D000799:Angioedema / Q000097:blood / Q000503:physiopathology; D004892:Erythema Multiforme / Q000097:blood / Q000503:physiopathology*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007704:Kininogens / Q000097:blood / Q000502:physiology*; D008297:Male; D012713:Serum Sickness / Q000097:blood / Q000503:physiopathology; D014581:Urticaria / Q000097:blood / Q000503:physiopathology
chemical_list: D007704:Kininogens