Chronic idiopathic urticaria (CIU) is characterized by itching wheals lasting for more than six weeks with unknown etiology. Mast cell activation has been suggested to be the pivotal mechanism behind CIU. Mast cell activation leads to not only the release of histamine and leukotrienes, but also production of proinflammatory cytokines that promote inflammatory response. Cytokines are implicated not only in recruitment of inflammatory cells to the target site, but also in triggering the cell signaling that leads to release of histamine and eicosanoids. Transforming growth factor β (TGF-β) and interleukin 10 (IL-10) are two anti-inflammatory cytokines that are implicated in the pathogenesis of urticaria.
Patients and methods:
This hospital-based case-control study was comprised of 90 patients with CIU. The patients were randomly selected from the outpatient clinic of allergy and immunology in the Children’s Medical Center Hospital, the Pediatrics Center of Excellence in Tehran, Iran. One hundred and forty healthy subjects were also randomly selected (Polymerase chain reaction (PCR) was done to determine the genotype at 5 polymorphic sites; TGF-β (codon10C/T and codon25G/C) and IL-10 (-1082G/A, -819C/T, and -592C/A).
The C allele at codon 25 of TGF-β was more prevalent in CIU patients compared to controls (OR = 9.5, 95% CI = 5.4-16.8, P<0.001). Genotypes of CT and CG at 10 and 25 codons of TGF-β gene, respectively, and AG, CT, and CA for loci of -1082, -819, and -592 of IL-10 gene were significantly higher in CIU patients (P<0.001). In haplotype analysis, frequency of TGF-β haplotypes differed between patients with CIU and controls; CC haplotype was overrepresented, while CG and TG haplotypes were underrepresented (P<0.001).
These results suggest that TGF-β and IL-10 genetic variability could contribute to susceptibility to CIU. Additionally, patients with CIU seem to have genotypes leading to high production of TGF-β and IL-10. Further studies are needed to draw firmer conclusions regarding the genetic background of patients with CIU and the role of immunoregulatory cytokines in CIU.