title: Increased circulating levels of tissue kallikrein in systemic sclerosis correlate with microvascular involvement.
abstract: BACKGROUND
  In systemic sclerosis (SSc) the lack of an angiogenic response to hypoxia may be due to inappropriate synthesis of angiogenic and angiostatic factors. Tissue kallikrein (t-kallikrein), regulating the kallikrein-kinin system and acting on the microcirculation, is a potent angiogenic agent, and kallistatin is its natural inhibitor.
  
  
  OBJECTIVE
  To evaluate, in patients with SSc, t-kallikrein and kallistatin levels and their correlation with clinical features and measures of microvascular involvement.
  
  
  METHODS
  Serum levels of t-kallikrein and kallistatin (ELISA) and t-kallikrein skin expression (immunohistochemistry) were studied in patients with SSc, and evaluated for subset (dSSc or lSSc), clinical and immunological features, and microvascular involvement (ulcers, telangiectasias, nailfold videocapillaroscopy).
  
  
  RESULTS
  Circulating levels of t-kallikrein were higher in SSc than in controls (p<0.001). T-kallikrein did not differ between lSSc and dSSc, although it was higher in lSSc than in controls (p<0.001).T-kallikrein levels were higher in patients with early and active capillaroscopic pattern than in those with late pattern (p = 0.019 and 0.023). Patients with giant capillaries and capillary microhaemorrhages had higher t-kallikrein concentrations than patients with architectural derangement (p = 0.04). No differences in kallistatin levels were detected between patients with SSc and controls, or between lSSc and dSSc. In early SSc skin, the presence of t-kallikrein was found in endothelial and in perivascular inflammatory cells, while no staining in skin of advanced SSc was detected.
  
  
  CONCLUSIONS
  T-kallikrein levels are increased in patients with SSc, particularly in lSSc, and are associated with early and active capillaroscopic patterns. T-kallikrein may play a part in SSc microvascular changes.
authors.affiliation: Department of Medicine, Division of Rheumatology, University of Florence, Viale G Pieraccini, 18-50139 Florence, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Del Rosso
authors.forename: O
authors.initials: O
authors.lastname: Distler
authors.forename: A F
authors.initials: AF
authors.lastname: Milia
authors.forename: C
authors.initials: C
authors.lastname: Emanueli
authors.forename: L
authors.initials: L
authors.lastname: Ibba-Manneschi
authors.forename: S
authors.initials: S
authors.lastname: Guiducci
authors.forename: M L
authors.initials: ML
authors.lastname: Conforti
authors.forename: S
authors.initials: S
authors.lastname: Generini
authors.forename: A
authors.initials: A
authors.lastname: Pignone
authors.forename: S
authors.initials: S
authors.lastname: Gay
authors.forename: P
authors.initials: P
authors.lastname: Madeddu
authors.forename: M
authors.initials: M
authors.lastname: Matucci-Cerinic
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D002196:Capillaries / Q000473:pathology; D002352:Carrier Proteins / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008833:Microcirculation; D020678:Microscopic Angioscopy / Q000379:methods; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000097:blood* / Q000473:pathology; D015843:Serpins / Q000097:blood; D012867:Skin / Q000378:metabolism; D020840:Tissue Kallikreins / Q000037:antagonists & inhibitors / Q000097:blood*
chemical_list: D001323:Autoantibodies; D002352:Carrier Proteins; D015843:Serpins; C051324:kallistatin; D020840:Tissue Kallikreins