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抗甲状腺过氧化物酶 IgG/总 IgE 比值:预测奥马珠单抗治疗慢性自发性荨麻疹反应的生物标志物。

Anti-TPO IgG/Total IgE Ratio: Biomarker for Omalizumab Response Prediction in Chronic Spontaneous Urticaria.

机构信息

Immunoallergology Department, Hospital de Santa Maria - Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.

Clínica Universitária de Imunoalergologia, Centro Académico de Medicina de Lisboa - Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.

出版信息

Int Arch Allergy Immunol. 2023;184(9):866-869. doi: 10.1159/000532021. Epub 2023 Aug 9.

DOI:10.1159/000532021
PMID:37557083
Abstract

BACKGROUND

According to recently published data, low total IgE, elevated IgG-anti-TPO, and a high IgG-anti-TPO/total IgE ratio are good biomarkers for subtype IIb autoimmune chronic spontaneous urticaria (CSU), which is frequently refractory to antihistamines and omalizumab.

OBJECTIVES

The aim of the study was to evaluate IgG-anti-TPO/total IgE ratio's utility in omalizumab response prediction.

METHODS

Retrospective study of CSU patients treated with omalizumab at a UCARE between January 2009 and February 2022. Patients were grouped according to response in the first 16 weeks of treatment: responders UAS7 < 7 versus partial/non-responders UAS7≥7. Total IgE, IgG-anti-TPO, and IgG-anti-TPO/total IgE ratio were compared. Other inflammatory biomarkers - eosinophils, basophils, C-reactive protein, erythrocyte sedimentation rate, and d-dimer - were analyzed.

STATISTICAL ANALYSIS

SPSS® (v25.0), p < 0.05 statistically significant.

RESULTS

Total of 175 patients, 140 (80%) women, median age 49 [9-88] years, mean CSU duration pre-omalizumab 5.6 ± 8.2 [0-54] years, omalizumab duration 3.2 ± 2.5 [0-12] years. 116 (66%) had angioedema, 77 (44%) inducible chronic urticaria, 60 (34%) atopy, 24 (14%) autoimmune disease. With omalizumab 300 mg q4 weeks, 69% were responders and 31% partial/non-responders. Although not reaching significant differences, mean total IgE values were lower and mean IgG-anti-TPO values were higher in partial/non-responders versus responders (152 vs. 242 kU/L, p = 0.207, and 38.3 vs. 25.7 U/mL, p = 0.408, respectively). A higher IgG-anti-TPO/total IgE ratio was significantly associated with poorer response to omalizumab (p = 0.040). A cut-off >0.154 increased 10 times the odd of poorer response [95% CI 4.62-22], AUC 0.872, p < 0.001, with 87.7% sensitivity, although the low specificity (22.4%) does not allow the assumption of response with values <0.154. Other laboratory biomarkers did not show significant differences between partial/non-responders versus responders.

CONCLUSIONS

A high IgG-anti-TPO/total IgE ratio was a good biomarker of poor response to omalizumab in our CSU cohort, with a cut-off >0.154 increasing 10 times the odd of poorer response.

摘要

背景

根据最近发表的数据,低总 IgE、升高的 IgG-抗 TPO 和高 IgG-抗 TPO/总 IgE 比值是 IIb 型自身免疫性慢性自发性荨麻疹(CSU)的良好生物标志物,这种荨麻疹常对抗组胺药和奥马珠单抗难治。

目的

本研究旨在评估 IgG-抗 TPO/总 IgE 比值在奥马珠单抗反应预测中的应用。

方法

对 2009 年 1 月至 2022 年 2 月在 UCARE 接受奥马珠单抗治疗的 CSU 患者进行回顾性研究。根据治疗第 16 周时的反应将患者分为两组:UAS7<7 的应答者与 UAS7≥7 的部分/无应答者。比较总 IgE、IgG-抗 TPO 和 IgG-抗 TPO/总 IgE 比值。还分析了其他炎症生物标志物——嗜酸性粒细胞、嗜碱性粒细胞、C 反应蛋白、红细胞沉降率和 D-二聚体。

统计学分析

采用 SPSS®(v25.0),p<0.05 具有统计学意义。

结果

共纳入 175 例患者,其中 140 例(80%)为女性,中位年龄 49[9-88]岁,平均奥马珠单抗治疗前 CSU 病程为 5.6±8.2[0-54]年,奥马珠单抗疗程为 3.2±2.5[0-12]年。116 例(66%)有血管性水肿,77 例(44%)有诱导性慢性荨麻疹,60 例(34%)有特应性,24 例(14%)有自身免疫性疾病。用奥马珠单抗 300mg q4w,69%为应答者,31%为部分/无应答者。尽管未达到显著差异,但部分/无应答者的平均总 IgE 值较低,平均 IgG-抗 TPO 值较高(152 vs. 242 kU/L,p=0.207,38.3 vs. 25.7 U/mL,p=0.408)。较高的 IgG-抗 TPO/总 IgE 比值与奥马珠单抗反应较差显著相关(p=0.040)。比值>0.154 会使反应较差的几率增加 10 倍[95%CI 4.62-22],AUC 为 0.872,p<0.001,敏感性为 87.7%,但特异性低(22.4%),不能仅根据比值<0.154 就假设会有反应。其他实验室生物标志物在部分/无应答者与应答者之间无显著差异。

结论

在我们的 CSU 队列中,高 IgG-抗 TPO/总 IgE 比值是奥马珠单抗反应不良的良好生物标志物,比值>0.154 会使反应不良的几率增加 10 倍。

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