RESUMO
BACKGROUND: Chronic idiopathic urticaria (CIU) is a complicated skin disease with unknown pathophysiology. MicroRNAs (miRNA) have been shown to be active in cellular regulation. The goal of this pilot study was to examine whether miRNAs may be involved in the regulation of CIU or as biomarkers for CIU. METHODS: Four groups of three patients each were selected: patients with either active hives or no hives and with positive or negative chronic urticaria (CU) index results. MiRNAs were isolated from patient plasma and analyzed by using miRNA microarray technology to determine the amount of each of the 2567 known human miRNAs. RESULTS: A total of 16 miRNAs were found to be differentially expressed in patients with active hives. Among them, five (2355-3p, 4264, 2355-5p, 29c-5p, and 361-3p) were significantly increased in samples with positive CU index results, which could be useful biomarkers for patients with chronic autoimmune urticaria. The miRNA data bases were used to find the targets of these selected miRNA sequences. These potential targets were then compared against a list of 154 urticaria-related genes. Twenty-five genes were found to match. These included eight that were significantly downregulated and eight that were significantly upregulated; however, seven of the eight downregulated genes (FBXL20, OPHN1, YPEL2, STARD9, EZH1, KLHL24, ING4) and five of the eight upregulated genes (BYSL, PNO1, ADAMTS9, STEAP4, SRGN) have no reported roles in signaling. For the 13 genes with reported roles in signaling, the following pathways were found: transforming growth factor beta signaling pathway (NRC31, KITLG, THBS1, CCL2), glucocorticoid receptor signaling pathway (NR3C1, SELE, CCL2), p53 signaling pathway (CCNG2, THBS1, CCL2), p21-activated kinase pathway (PAK1IP1, KITLG, CCL2), phosphoinositide-3 kinase protein kinase B signaling pathway (KITLG, CHRM, THBS1), and neuroactive ligand-receptor interaction (NRC31, HRH1, CHRM), which could play important roles in CIU. CONCLUSION: A better understanding of those genes with undefined function and simultaneous quantitation of both miRNAs and messenger RNAs are needed to fully understand CIU disease.
RESUMO
BACKGROUND: The skin prick test is the diagnostic procedure of choice for determination of immediate hypersensitivity. A wheal diameter of 3 mm or larger is generally accepted as the cutoff for a positive test result, although the validity of this assumption has not been rigorously demonstrated. OBJECTIVE: To determine the skin prick wheal size that best identifies clinical allergy to cat. METHODS: Forty-five patients referred for evaluation of rhinoconjunctivitis underwent determination of atopic status by skin testing using the Greer Dermapik device and a combination of other modalities, including history, in vitro determination of specific IgE level, and nasal challenge with standardized cat pelt extract. Parameters evaluated before and after nasal challenge included symptom score and nasal lavage tryptase and prostaglandin D (PGD2) levels. RESULTS: The widely accepted 3-mm wheal for a positive skin test result to cat is highly sensitive but only moderately specific for diagnosis of cat allergy as evaluated by history, specific IgE level, postchallenge symptom score, and tryptase and PGD2 levels. Optimal cutoffs for a positive skin test result to cat based on receiver operating characteristic analysis and 95% positive predictive value were 5.5 mm or greater for each of these parameters. When a true-positive result for cat allergy was defined as a combination of positive history, specific IgE level, postchallenge symptom score, and tryptase and PGD2 levels and a true-negative result as all of these parameters being negative, a 6-mm cutoff was able to distinguish cat allergic from cat nonallergic individuals. CONCLUSION: In a potentially allergic population undergoing skin prick testing with the Greer Dermapik using standardized extracts, a 3-mm skin prick wheal will overestimate the presence of cat allergy. A 6-mm wheal appears to distinguish those individuals who are cat allergic from those who are not.
