title: Increased activity of plasma and tissue kallikreins, plasma kininase II and salivary kallikrein in pemphigus foliaceus (fogo selvagem).
abstract: BACKGROUND
  Pemphigus foliaceus (PF) is an autoimmune blistering disease of unknown aetiology, which is endemic in Brazil. Although the pathogenesis of PF is still unknown, proteins of the contact system have been implicated.
  
  
  OBJECTIVE
  As the components of the kinin system may interact with those of the contact system, in this study we evaluated the plasma levels of high-molecular-weight kininogen (HK) and low-molecular-weight kininogen (LK), and the activity of plasma kallikrein, tissue kallikrein and kininase II in plasma of patients with PF presenting with Nikolsky's sign. As kidneys and salivary glands are relevant sources of tissue kallikrein for plasma, we also evaluated urinary/salivary kallikrein and urinary kininase II activities.
  
  
  METHODS
  Fifteen patients and 15 age- and sex-matched controls were studied. Kininogen levels were determined by enzyme-linked immunosorbent assay, and the activities of kallikreins and kininase II were determined using selective chromogenic substrates.
  
  
  RESULTS
  Compared with controls, plasma HK levels were decreased (P = 0.031), whereas the activities of plasma kallikrein, tissue kallikrein and kininase II in plasma, and the activity of salivary kallikrein, were increased in patients (P < 0.001 for each comparison). Plasma levels of LK and the activities of urinary kallikrein and urinary kininase II were not significantly different from controls.
  
  
  CONCLUSIONS
  Diminished levels of HK associated with increased activities of plasma kallikrein and kininase II indicate that the kinin system is activated at the systemic level in PF. As active plasma kallikreins may act on some proteins of the contact system, it is possible that the enzyme may contribute to blister formation. The further observation of an increased tissue kallikrein activity at the systemic and saliva levels may be interpreted as a systemic reflex of skin inflammation. Whether the activation of the kinin system is a cause or a consequence of blister formation needs further clarification.
authors.affiliation: Dermatology, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes 3900, Monte Alegre, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: T B
authors.initials: TB
authors.lastname: Rosatelli
authors.forename: A M
authors.initials: AM
authors.lastname: Roselino
authors.forename: R
authors.initials: R
authors.lastname: Dellalibera-Joviliano
authors.forename: M L
authors.initials: ML
authors.lastname: Reis
authors.forename: E A
authors.initials: EA
authors.lastname: Donadi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000032:analysis* / Q000097:blood / Q000652:urine; D007704:Kininogens / Q000097:blood; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D010392:Pemphigus / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000097:blood* / Q000652:urine; D020842:Plasma Kallikrein / Q000032:analysis; D012463:Saliva / Q000201:enzymology*; D020840:Tissue Kallikreins / Q000097:blood
chemical_list: D007704:Kininogens; D007703:Peptidyl-Dipeptidase A; D007610:Kallikreins; D020842:Plasma Kallikrein; D020840:Tissue Kallikreins