C‐reactive protein (CRP) rs3093059C predicts poor mizolastine response in chronic spontaneous urticaria patients with elevated serum CRP level

Abstract

Chronic spontaneous urticaria (CSU) is a frequent disorder with recurrent itchy wheals and/or angioedema, and nearly 35% patients respond poorly to non‐sedating H1 antihistamine treatment. CRP gene encodes the C‐reactive protein, which is involved in the pathogenesis of CSU. To investigate the impacts of CRP polymorphisms on the susceptibility and therapeutic efficacy in the South Han CSU patients, we enrolled 145 CSU patients in our study. After 4‐week non‐sedating H1 antihistamine monotherapy treatment, more than 50% reduction of the severity score is considered as effective, or else non‐effective. The CRP rs3093059T/C and rs2794521G/A genotypes of patients were determined by Sequenom MassARRAY. Functional studies including relative luciferase assay and β‐hexosaminidase assay were conducted in HEK293T cells or RBL‐2H3 cells to explore the function of variants. Forty (62.50%) CSU patients were effective when treated with mizolastine, and 55 (72.4%) patients were effective in the desloratadine group. We found that the patients carried with rs3093059TT genotype were significantly associated with good response (OR = 4.20, P = 0.015), had lower serum CRP, IL‐6 and TNF‐α levels than the CT/CC genotypes. In vitro, the rs3093059C allele exhibited significantly higher luciferase activity than wild allele (P < 0.001). From the β‐hexosaminidase assay, we observed the inhibiting degranulation effects by mizolastine and this effect is weakened when with a higher dose CRP in RBL‐2H3 cells. Our findings suggested that CSU patients carrying the rs3093059C allele may respond poorly to mizolastine with elevated serum CRP level.

Predictors of treatment response in chronic spontaneous urticaria

“…Of note, a study by Yan et al revealed that the single nucleotide polymorphism rs216008 mutation may negatively affect the response to the sgAH desloratadine 26 . Additionally, certain CRP single nucleotide polymorphisms, such as those carrying the rs3093059C allele, may be linked to elevated serum CRP levels and a poor response to the sgAH mizolastine 27 …”

“…26 Additionally, certain CRP single nucleotide polymorphisms, such as those carrying the rs3093059C allele, may be linked to elevated serum CRP levels and a poor response to the sgAH mizolastine. 27 CIndU, for example symptomatic dermographism and delayed pressure urticaria, may coexist with CSU, and its presence appears to indicate a longer duration of CSU and nonresponse to sgAHs. Indeed, CIndU is a common comorbidity of sgAH-refractory CSU, occurring in 24% of CSU patients.…”

Advanced Biomarkers: Therapeutic and Diagnostic Targets in Urticaria

“…CRP is a marker of acute inflammation, and TNF-α and IL-6 can stimulate liver cells to secrete CRP. In CU, serum IL-6 and CRP are positively correlated with disease severity and itching [96]. In addition, studies have found that CRP, D-dimer, and MMP-9 are related, indicating that inflammation and the coagulation system are relevant [43].…”

“…It can predict the occurrence of AICU and prevent it [118]. CRP encodes CRP, and a recent study found that CRP rs3093059C predicts a poor mizolastine effect [119]. A research reported that C5AR1 −1,330T/G polymorphism predicts a poor desloratadine effect [120].…”

A Systematic Review and Meta-Analysis of Health Utility Estimates in Chronic Spontaneous Urticaria

“…First, compared with the EQ-5D, the SF-6D has an additional dimension of vitality. Fatigue lack of sleep or insomnia are commonly reported in patients with CSU due to its constant itch accompanied by the collapse of urticarial (37)(38)(39), which has considerable influence on the dynamic of vitality. Second, the two instruments have different foci.…”