title: Plasma of patients with chronic urticaria shows signs of thrombin generation, and its intradermal injection causes wheal-and-flare reactions much more frequently than autologous serum.
abstract: BACKGROUND
  Several aspects of the pathogenesis of chronic urticaria (CU) remain contradictory. Autologous serum skin tests (ASSTs) and in vitro histamine release assays seem to look into distinct aspects of the disease, and the specificity of ASST has been questioned.
  
  
  OBJECTIVE
  We compared the autologous plasma skin test (APST) with ASST to detect autoreactivity in patients with CU. The clotting process was investigated as well by measuring in vivo thrombin generation.
  
  
  METHODS
  A total of 96 adults with CU underwent ASST; 71 of them underwent APST with Na citrate-anticoagulated plasma. Prothrombin fragment 1+2 plasma levels were measured by a sandwich ELISA in Na citrate-anticoagulated plasmas from 28 patients and 27 controls.
  
  
  RESULTS
  Fifty-one of 96 (53%) patients scored positive on ASST, whereas 61 of 71 (86%) patients scored positive on APST (21/30 [70%] ASST-negative and 40/41 [98%] ASST-positive). Plasma prothrombin fragment 1+2 was higher in patients than controls (3.06 [SD 3.36] vs 0.80 [0.34]; P < .001) and in ASST-positive/APST-positive than in ASST-negative/APST-positive patients (3.89 [SD 3.68] vs 1.33 [1.64]; P = 0.058) and was directly related to urticaria severity (r = 0.37; P < .05).
  
  
  CONCLUSIONS
  Most patients with CU are positive on APST-Na citrate. CU is associated with the generation of thrombin, a serine protease able to activate mast cells and to cause relevant increase in permeability of endothelium. APST and ASST only partially depend on the presence of circulating antibodies to FcepsilonRI or to IgE.
  
  
  CONCLUSIONS
  These findings provide new insights into the pathogenesis of CU and suggest new therapeutic opportunities for treating this disease.
authors: Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano (MI), Italy. r.asero@libero.it
authors: Riccardo
authors: R
authors: Asero
authors: Alberto
authors: A
authors: Tedeschi
authors: Piersandro
authors: P
authors: Riboldi
authors: Massimo
authors: M
authors: Cugno