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本文引用的文献

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Dupilumab-related type 1 diabetes in a patient with atopic dermatitis: a case report.一名特应性皮炎患者中与度普利尤单抗相关的1型糖尿病:病例报告
Diabetol Int. 2021 Aug 10;13(1):300-303. doi: 10.1007/s13340-021-00526-1. eCollection 2022 Jan.
2
Screening for Prediabetes and Type 2 Diabetes: US Preventive Services Task Force Recommendation Statement.筛查糖尿病前期和 2 型糖尿病:美国预防服务工作组推荐声明。
JAMA. 2021 Aug 24;326(8):736-743. doi: 10.1001/jama.2021.12531.
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Pembrolizumab-induced diabetes.派姆单抗引起的糖尿病。
Endokrynol Pol. 2021;72(4):414-415. doi: 10.5603/EP.a2021.0053. Epub 2021 May 31.
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Atezolizumab-induced pure red cell aplasia.阿替利珠单抗诱导的纯红细胞再生障碍性贫血。
Br J Haematol. 2021 Apr;193(1):10. doi: 10.1111/bjh.17259. Epub 2021 Feb 14.
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Engineering therapeutic antibodies for patient safety: tackling the immunogenicity problem.为患者安全工程治疗性抗体:解决免疫原性问题。
Protein Eng Des Sel. 2020 Sep 14;33. doi: 10.1093/protein/gzaa025.
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T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation-Updated Consensus and Review 2020.T 细胞依赖性蛋白治疗药物免疫原性的临床前评估和缓解策略——2020 年更新共识和综述。
Front Immunol. 2020 Jun 30;11:1301. doi: 10.3389/fimmu.2020.01301. eCollection 2020.
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Mechanisms of Dupilumab.度普利尤单抗的作用机制。
Clin Exp Allergy. 2020 Jan;50(1):5-14. doi: 10.1111/cea.13491. Epub 2019 Sep 30.
8
Programmed Cell Death-1 Monoclonal Antibody Therapy and Type 1 Diabetes Mellitus: A Review of the Literature.程序性细胞死亡蛋白1单克隆抗体疗法与1型糖尿病:文献综述
J Pharm Pract. 2021 Feb;34(1):133-140. doi: 10.1177/0897190019850929. Epub 2019 Jul 3.
9
Immunogenicity and other problems associated with the use of biopharmaceuticals.生物制药的免疫原性和其他问题。
Ther Adv Drug Saf. 2011 Jun;2(3):113-28. doi: 10.1177/2042098611406318.
10
Definition of high-risk type 1 diabetes HLA-DR and HLA-DQ types using only three single nucleotide polymorphisms.仅使用三个单核苷酸多态性定义高危 1 型糖尿病 HLA-DR 和 HLA-DQ 类型。
Diabetes. 2013 Jun;62(6):2135-40. doi: 10.2337/db12-1398. Epub 2013 Feb 1.

非遗传易患患者中与度普利尤单抗相关的糖尿病及症状逆转

Dupilumab-Related Diabetes Mellitus With Reversal of Symptoms in a Non-genetically Predisposed Patient.

作者信息

Blaylock Tanner C, Leon Daniel

机构信息

College of Allopathic Medicine, Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, USA.

Internal Medicine, Chen Senior Medical Center, Plantation, USA.

出版信息

Cureus. 2024 Jan 27;16(1):e53080. doi: 10.7759/cureus.53080. eCollection 2024 Jan.

DOI:10.7759/cureus.53080
PMID:38414708
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10897062/
Abstract

Dupilumab is a fully humanized monoclonal antibody that binds to IL-4 receptors and blocks IL-4 and IL-13 mediated T-helper 2 (Th2) responses. Dupilumab is estimated to be used by over 600,000 patients worldwide for the treatment of atopic dermatitis and other immunologic conditions. Recently, a 66-year-old male patient being treated for atopic dermatitis with dupilumab presented to the clinic with complaints of polyuria and polydipsia. Upon initial testing, the patient was found to have considerable hyperglycemia. Upon genetic testing, he showed no predisposition for autoimmune diabetes and was negative for type I diabetes mellitus-associated human leukocyte antigen (HLA) genes. After immediate cessation of dupilumab, and with subsequent insulin therapy, the patient was able to obtain glycemic control. Following taper and eventual cessation of insulin therapy and over the course of seven months, the patient was able to achieve a full resolution of symptoms and his glycosylated hemoglobin (HgBA1c) levels returned to normal ranges. This case represents only the second documented case of dupilumab-induced diabetes mellitus and is the first known documented case of dupilumab-induced diabetes mellitus in a non-genetically predisposed individual. This case also describes a previously unobserved spontaneous resolution of symptoms upon cessation of the drug. This case further illustrates the potential existence of immunogenic or immunomodulatory side effects of the monoclonal antibody dupilumab that can affect patients who are both genetically and non-genetically predisposed to autoimmune diabetes mellitus.

摘要

度普利尤单抗是一种全人源单克隆抗体,它与白细胞介素-4(IL-4)受体结合,阻断IL-4和IL-13介导的辅助性T细胞2(Th2)反应。据估计,全球有超过60万名患者使用度普利尤单抗治疗特应性皮炎和其他免疫性疾病。最近,一名66岁的男性患者使用度普利尤单抗治疗特应性皮炎,因多尿和烦渴到诊所就诊。初步检查发现该患者有明显的高血糖。基因检测显示,他没有自身免疫性糖尿病的易感性,且I型糖尿病相关的人类白细胞抗原(HLA)基因检测为阴性。立即停用度普利尤单抗并随后进行胰岛素治疗后,患者血糖得到控制。在逐渐减少并最终停止胰岛素治疗后的七个月里,患者症状完全缓解,糖化血红蛋白(HgBA1c)水平恢复到正常范围。该病例是度普利尤单抗诱导的糖尿病的第二例有记录的病例,也是首例已知的在非遗传易感性个体中由度普利尤单抗诱导的糖尿病病例。该病例还描述了停药后症状出现了此前未观察到的自发缓解。该病例进一步说明了单克隆抗体度普利尤单抗可能存在免疫原性或免疫调节副作用,这些副作用可能影响遗传和非遗传易感性的自身免疫性糖尿病患者。