title: Evidence for aberrant regulation of the p21Ras pathway in PBMCs of patients with chronic idiopathic urticaria.
abstract: BACKGROUND
  Recent data suggest that a subpopulation of patients with chronic urticaria has an autoimmune disorder. Aberrant expression and regulation of the p21Ras pathway has been reported in lymphoid cells in a variety of systemic autoimmune diseases but not in chronic idiopathic urticaria (CIU).
  
  
  OBJECTIVE
  The aim of this study was to examine the expression, regulation, and function of the p21Ras pathway in patients with CIU.
  
  
  METHODS
  Twenty-four patients with CIU and 14 control subjects were enrolled. All patients and 9 control subjects were intradermally injected with autologous serum. PBMCs were isolated, and the p21Ras and its regulatory proteins were studied.
  
  
  RESULTS
  We found increased expression of the p21ras proto-oncogene in patients with CIU. This was associated with a low expression of the p21Ras stimulatory element human son of sevenless (hSOS1) but normally expressed p21Ras inhibitory element p120GTPase-activating protein. The basal nonstimulated membrane/cytoplasmic ratio of hSOS1, which indicates the p21Ras pathway activity, was higher in patients compared with that seen in control subjects. Moreover, after stimulation, both patients and control subjects decreased their hSOS1 membrane/cytoplasmic ratio. The magnitude of this decrease was much higher in patients than in control subjects: 14- and approximately 2-fold, respectively. The basal and stimulated activities of the p21Ras downstream key regulatory enzyme mitogen-activated protein kinase were comparable in patients and control subjects, as was their in vitro mitogen-stimulated lymphocyte proliferation.
  
  
  CONCLUSIONS
  Our data demonstrate for the first time an aberrant signaling through the p21Ras pathway in lymphocytes of patients with CIU. This finding further supports the autoimmune basis of this disease.
authors.affiliation: Allergy and Clinical Immunology Unit, Sapir Medical Center, Kefar Saba, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Confino-Cohen
authors.forename: Dorit
authors.initials: D
authors.lastname: Aharoni
authors.forename: Arnon
authors.initials: A
authors.lastname: Goldberg
authors.forename: Irena
authors.initials: I
authors.lastname: Gurevitch
authors.forename: Andreas
authors.initials: A
authors.lastname: Buchs
authors.forename: Mordechai
authors.initials: M
authors.lastname: Weiss
authors.forename: Joshua
authors.initials: J
authors.lastname: Weissgarten
authors.forename: Micha J
authors.initials: MJ
authors.lastname: Rapoport
mesh_terms: D000328:Adult; D015551:Autoimmunity; D002908:Chronic Disease; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D020837:SOS1 Protein / Q000378:metabolism; D015398:Signal Transduction; D014581:Urticaria / Q000276:immunology* / Q000378:metabolism*; D020729:p120 GTPase Activating Protein / Q000378:metabolism
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D020837:SOS1 Protein; D020729:p120 GTPase Activating Protein; D020928:Mitogen-Activated Protein Kinases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)