Association of ORAI1 gene polymorphisms with chronic spontaneous urticaria and the efficacy of the nonsedating H1 antihistamine desloratadine

Li, Jie; Guo, Aiyuan; Chen, Wangqing; Bin, Lianghua; He, Yijing; Zhu, Wu; Peng, Cong; Yan, Siyu; Chen, Mingliang; Zhang, Jianglin; Su, Juan; Man, Yi; Liu, Zhao‐Qian; Zhang, Wei; Zeng, Weiqi; Leung, Donald Y.M.; Chen, Xiang

doi:10.1016/j.jaci.2016.10.017

Cited by 24 publications

(21 citation statements)

References 14 publications

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“…The efficacy of the antihistamines was evaluated using the weekly urticaria activity score (UAS7) by two professional dermatologists independently, both at baseline and after antihistamine monotherapy for 4 weeks. Responders were defined as those patients who had an improvement in UAS7 scores above 50% after the 4‐week treatment …”

Section: Methodsmentioning

confidence: 99%

“…After washing three times with HBSS, phorbol‐12‐myristate‐13‐acetate (PMA) (100 nmol/L, Sigma, St. Louis, MO) and ionomycin (1 μmol/L, Sigma) were used to stimulate cell degranulation for 4 hours. Subsequently, cells and supernatant were collected to evaluate the β‐hexosaminidase release ratio by microplate spectrophotometer at 405 nm, and the data were analysed by comparing the supernatant release rate to the total β‐hexosaminidase . Meanwhile, cytokines such as IL‐6 and TNF‐α in the supernatant were detected via ELISA according to the manufacturer's instructions (BD Biosciences).…”

Section: Methodsmentioning

confidence: 99%

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

Yan

Chen

Peng

et al. 2019

Experimental Dermatology

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Yan

Chen

Peng

et al. 2019

Experimental Dermatology

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“…Calcium-release-activated calcium modulator 1 (ORAI1) is a subunit of calcium-release-activated calcium channels, which mediate calcium influx and mast cell degranulation [163]. A study has demonstrated that different single nucleotide polymorphisms in the ORAI1 gene are associated with an increased risk of CSU and better response to desloratadine [164]. Thus, targeting of ORAI1 via silencing RNAs might be of therapeutic potential in CSU [163].…”

Section: Other Possıble Targets For Treatmentmentioning

confidence: 99%

Targeted Therapy for Chronıc Spontaneous Urtıcarıa: Ratıonale and Recent Progress

Giménez‐Arnau

Salman

2020

Drugs

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Chronic spontaneous urticaria (CSU) is characterized by the presence of wheals, angioedema, or both for at least 6 weeks. It may persist for a long time-up to 50% of the patients have been reported to be symptomatic 5 years after the onset. Some patients can suffer more than one episode of CSU during their lifetime. Considering the recurrences, disabling symptoms, and significant impact on quality of life, proper and effective treatment of CSU is critical. The use of antihistamines (AHs) is still the mainstay of treatment. However, given the low rates of response to AHs (38.6% and 63.2% to standard doses and higher doses, respectively), the complete control of symptoms seems difficult to attain. The use of omalizumab for CSU has been a major breakthrough in the care of patients with CSU. However, the partial response and lack of response to omalizumab in a subgroup of patients, as high as 70% in some studies, make the development of alternative treatments desirable. Ever-increasing knowledge on the pathogenesis is making new target molecules available and enabling drug development for CSU. In addition to drug repurposing as in anti-IL-4/13, IL-5, and IL-17 antibodies, novel targeted therapy options such as ligelizumab and Bruton's tyrosine kinase inhibitors are currently undergoing clinical trials and will be available in the near future. This article reviews the current challenges in the treatment of CSU, the pathogenesis and potential target molecules, and the rationale for novel treatments and their rapidly developing status.

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“…In a mouse study it was reported that ORAI1 is essential for mast cell degranulation. 84 Li et al 85 reported the association of ORAI1 gene polymorphisms (ORAI1 gene single nucleotide polymorphisms rs12320939 and rs3741596) with CSU in the South Han Chinese population. The rs3741596A allele on the ORAI1 gene, for example, was associated with enhanced degranulation activity.…”

Section: Omalizumab Therapy In Patients With Csumentioning

confidence: 99%

“…ORAI1 gene polymorphisms are associated with CSU in the South Han Chinese population. 85 analysis with human samples, the complex immunologic mechanisms of AD have been revealed gradually. The heterogeneity of AD pathophysiology is also becoming apparent.…”

Section: Geneticsmentioning

confidence: 99%

Advances in atopic dermatitis and urticarial in 2016

Honda

Nomura

Kabashima

2017

Journal of Allergy and Clinical Immunology

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This review highlights recent key advances in the pathology and therapies of inflammatory skin diseases, focusing on atopic dermatitis (AD) and chronic spontaneous urticaria (CSU). Regarding AD, transcriptomic analysis with human samples revealed different immune profiles between childhood and adult AD. Phase III clinical trials of dupilumab, an anti-IL-4 receptor α antibody, in the treatment of AD have successfully finished, and dupilumab will appear in clinical practice as the first biologic for AD in 2017. In addition, a novel biologic that targets IL-31 shows promising results in a phase II trial. As for the skin microbiome study, novel insights into the mechanisms of microbial dysbiosis, such as colonization of Staphylococcus aureus, a common feature of AD, were proposed. Regarding CSU, autoreactive CD4 T cells that react to FcεRI were discovered, which might contribute to the development of CSU. These findings provide new insights into the pathogenesis of AD and CSU and will lead to more specific and personalized treatments.

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Association of ORAI1 gene polymorphisms with chronic spontaneous urticaria and the efficacy of the nonsedating H1 antihistamine desloratadine

Cited by 24 publications

References 14 publications

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

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

Targeted Therapy for Chronıc Spontaneous Urtıcarıa: Ratıonale and Recent Progress

Advances in atopic dermatitis and urticarial in 2016

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