西妥昔单抗诱导的过敏反应及针对α-1,3-半乳糖的特异性IgE

Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose.

作者信息

Chung Christine H, Mirakhur Beloo, Chan Emily, Le Quynh-Thu, Berlin Jordan, Morse Michael, Murphy Barbara A, Satinover Shama M, Hosen Jacob, Mauro David, Slebos Robbert J, Zhou Qinwei, Gold Diane, Hatley Tina, Hicklin Daniel J, Platts-Mills Thomas A E

机构信息

Division of Hematology/Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, USA.

出版信息

N Engl J Med. 2008 Mar 13;358(11):1109-17. doi: 10.1056/NEJMoa074943.

DOI:10.1056/NEJMoa074943

PMID:18337601

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2361129/

Abstract

BACKGROUND

Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, is approved for use in colorectal cancer and squamous-cell carcinoma of the head and neck. A high prevalence of hypersensitivity reactions to cetuximab has been reported in some areas of the United States.

METHODS

We analyzed serum samples from four groups of subjects for IgE antibodies against cetuximab: pretreatment samples from 76 case subjects who had been treated with cetuximab at multiple centers, predominantly in Tennessee, Arkansas, and North Carolina; samples from 72 control subjects in Tennessee; samples from 49 control subjects with cancer in northern California; and samples from 341 female control subjects in Boston.

RESULTS

Among 76 cetuximab-treated subjects, 25 had a hypersensitivity reaction to the drug. IgE antibodies against cetuximab were found in pretreatment samples from 17 of these subjects; only 1 of 51 subjects who did not have a hypersensitivity reaction had such antibodies (P<0.001). IgE antibodies against cetuximab were found in 15 of 72 samples (20.8%) from control subjects in Tennessee, in 3 of 49 samples (6.1%) from northern California, and in 2 of 341 samples (0.6%) from Boston. The IgE antibodies were shown to be specific for an oligosaccharide, galactose-alpha-1,3-galactose, which is present on the Fab portion of the cetuximab heavy chain.

CONCLUSIONS

In most subjects who had a hypersensitivity reaction to cetuximab, IgE antibodies against cetuximab were present in serum before therapy. The antibodies were specific for galactose-alpha-1,3-galactose.

摘要

背景

西妥昔单抗是一种针对表皮生长因子受体的嵌合型鼠-人IgG1单克隆抗体，已被批准用于治疗结直肠癌和头颈部鳞状细胞癌。在美国的一些地区，已报道西妥昔单抗过敏反应的高发生率。

方法

我们分析了四组受试者血清样本中的抗西妥昔单抗IgE抗体：来自76例在多个中心接受西妥昔单抗治疗的病例受试者的治疗前样本，这些中心主要位于田纳西州、阿肯色州和北卡罗来纳州；来自田纳西州72例对照受试者的样本；来自北加利福尼亚州49例癌症对照受试者的样本；以及来自波士顿341例女性对照受试者的样本。

结果

在76例接受西妥昔单抗治疗的受试者中，25例对该药物有过敏反应。在其中17例受试者的治疗前样本中发现了抗西妥昔单抗IgE抗体；在51例无过敏反应的受试者中，只有1例有此类抗体（P<0.001）。在田纳西州对照受试者的72份样本中有15份（20.8%）、北加利福尼亚州的49份样本中有3份（6.1%）以及波士顿的341份样本中有2份（0.6%）发现了抗西妥昔单抗IgE抗体。这些IgE抗体被证明对一种寡糖半乳糖-α-1,3-半乳糖具有特异性，该寡糖存在于西妥昔单抗重链的Fab部分。