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.
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), phosphoinosi- tide-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.
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.
Heat map of differentially expressed microRNAs (miRNA) by hives status. Only those miRNAs whose level of expression differed at a given p value are shown. The first six columns represent patients who were negative for hives; the last six columns represent patients with active hives. Different miRNAs are clustered according to the degree of similarity in the level of expression.