在多发性硬化症患者中，与那他珠单抗相关的过敏样反应与 HLA Ⅱ类等位基因相关。

Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles.

机构信息

Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.

出版信息

Neurol Neuroimmunol Neuroinflamm. 2014 Dec 11;1(4):e47. doi: 10.1212/NXI.0000000000000047. eCollection 2014 Dec.

DOI:10.1212/NXI.0000000000000047

PMID:25520955

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4268037/

Abstract

OBJECTIVES

We aimed to investigate potential associations between human leukocyte antigen (HLA) class I and class II alleles and the development of anaphylactic/anaphylactoid reactions in patients with multiple sclerosis (MS) treated with natalizumab.

METHODS

HLA class I and II genotyping was performed in patients with MS who experienced anaphylactic/anaphylactoid reactions and in patients who did not develop infusion-related allergic reactions following natalizumab administration.

RESULTS

A total of 119 patients with MS from 3 different cohorts were included in the study: 54 with natalizumab-related anaphylactic/anaphylactoid reactions and 65 without allergic reactions. HLA-DRB113 and HLA-DRB114 alleles were significantly increased in patients who developed anaphylactic/anaphylactoid reactions (p M-H = 3 × 10(-7); odds ratio [OR]M-H = 8.96, 95% confidence interval [CI] = 3.40-23.64), with a positive predictive value (PPV) of 82%. In contrast, the HLA-DRB1*15 allele was significantly more represented in patients who did not develop anaphylactic/anaphylactoid reactions to natalizumab (p M-H = 6 × 10(-4); ORM-H = 0.2, 95% CI = 0.08-0.50), with a PPV of 81%.

CONCLUSIONS

HLA-DRB1 genotyping before natalizumab treatment may help neurologists to identify patients with MS at risk for developing serious systemic hypersensitivity reactions associated with natalizumab administration.

摘要

目的

我们旨在研究人类白细胞抗原（HLA）I 类和 II 类等位基因与接受那他珠单抗治疗的多发性硬化症（MS）患者发生过敏/过敏样反应的潜在相关性。

方法

对发生过敏/过敏样反应的 MS 患者和接受那他珠单抗治疗后未发生输注相关过敏反应的患者进行 HLA I 类和 II 类基因分型。

结果

本研究共纳入了来自 3 个不同队列的 119 名 MS 患者：54 名患者发生了那他珠单抗相关的过敏/过敏样反应，65 名患者未发生过敏反应。发生过敏/过敏样反应的患者 HLA-DRB113 和 HLA-DRB114 等位基因明显增加（p M-H = 3×10(-7)；优势比[OR]M-H = 8.96，95%置信区间[CI] = 3.40-23.64），阳性预测值（PPV）为 82%。相反，未发生那他珠单抗过敏/过敏样反应的患者 HLA-DRB1*15 等位基因明显更为多见（p M-H = 6×10(-4)；OR M-H = 0.2，95%CI = 0.08-0.50），PPV 为 81%。