Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 109, Issue 2, Pages 349-356Publisher
MOSBY, INC
DOI: 10.1067/mai.2002.121314
Keywords
human; signal transduction; T lymphocytes; chronic idiopathic urticaria; autoinummity; p21Ras; human son ofseven-less; p120GTPase-activating protein
Categories
Ask authors/readers for more resources
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). Objectives: 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 protooncogene 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. Conclusion: 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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available