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IgG4 anti‐infliximab in treated patients: Clinical impact and temporal evolution

机译：治疗患者中IgG4抗英夫利昔单抗：临床影响和时间演变

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Abstract Background Infliximab (IFX) carries potential risk of immunogenicity with the production of anti‐drug antibodies (ADA). ADA may belong to different isotypes and are usually measured by ELISA bridging assay. This test is not designed to detect IgG4 antibodies. The aim was to measure IgG4 anti‐IFX antibodies in a cohort of IFX‐treated patients and to evaluate their relationship with ADA and their clinical impact. Methods Anti‐drug antibodies were detected using a bridging ELISA in the serum of 222 treated patients with different clinical outcomes to IFX. The same samples were analyzed for IgG4 anti‐IFX antibodies using an experimental ImmunoCAP assay with reduced serum IgG4 background levels. A longitudinal evaluation was performed in a subgroup of 38 patients to define the temporal evolution of IgG4 anti‐IFX. Results IgG4 anti‐IFX was found in 26.6% of patients. Eighty of 222 patients were ADA+ (36%) and the majority (57/80, 71.3%) had IgG4 anti‐IFX. Two IgG4‐positive but ADA‐negative patients were identified. IgG4 anti‐IFX levels correlated with the serum levels of ADA. IgG4 anti‐IFX was more common in both reactive and nonresponder patients than in tolerant/responder patients. Patients who had experienced IgE‐mediated reactions displayed significantly higher IgG4 anti‐IFX than IgE‐negative reactive patients. The majority of patients tested positive for IgG4 anti‐IFX after the first seven infusions. Conclusions IgG4 anti‐IFX is common in treated patients and a large part of ADA producing patients produce IgG4 antibodies. The IgG4 anti‐IFX response does not prevent hypersensitivity reactions to IFX and correlates with the IgE anti‐IFX response.
机译：摘要背景Nigiximab（IFX）携带抗药物抗体（ADA）的潜在免疫原性风险。 ADA可能属于不同的同种型，并且通常通过ELISA桥接测定来测量。该测试不设计用于检测IgG4抗体。目的是测量INFX治疗患者队列中的IgG4抗IFX抗体，并评估与ADA的关系及其临床影响。方法使用222例治疗患者的血清中的桥接ELISA检测抗药物抗体，对IFX的不同临床结果。使用具有减少的血清IgG4背景水平的实验免疫焦点测定分析了IgG4抗IFX抗体的相同样品。在38名患者的亚组中进行纵向评估，以定义IgG4抗IFX的时间演变。结果IgG4抗IFX在26.6％的患者中发现。 222名患者的八十次患者是ADA +（36％），大多数（57/80,71.3％）具有IgG4抗IFX。鉴定了两种IgG4阳性但ADA阴性患者。 IgG4抗IFX水平与ADA的血清水平相关。 IgG4抗IFX在反应性和非响应者患者中更常见，而不是耐受性/响应者患者。经历了IgE介导的反应的患者显着高于IgG4抗IFX显着高于IgE阴性反应患者。大多数患者在前七次输注后测试了IgG4抗IFX阳性。结论IgG4抗IFX在治疗患者中是常见的，并且大部分ADA生产患者产生IgG4抗体。 IgG4抗IFX反应不会阻止对IFX的过敏反应，并与IgE抗IFX响应相关。

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  • 来源
    《Allergy》 |2018年第11期|共10页
  • 作者

    Vultaggio A.; Nencini F.; Carraresi A.; Pratesi S.; Movérare R.; Eriksson C.; Venemalm L.; Maggi E.; Matucci A.;

  • 作者单位

    Immunoallergology Unit Department of BiomedicineCareggi University HospitalFlorence Italy;

    Centre for Research Transfer and High Education DENOTHE and Department of Experimental and Clinical;

    Immunoallergology Unit Department of BiomedicineCareggi University HospitalFlorence Italy;

    Centre for Research Transfer and High Education DENOTHE and Department of Experimental and Clinical;

    Thermo Fisher Scientific ImmunoDiagnosticsUppsala Sweden;

    Thermo Fisher Scientific ImmunoDiagnosticsUppsala Sweden;

    Thermo Fisher Scientific ImmunoDiagnosticsUppsala Sweden;

    Centre for Research Transfer and High Education DENOTHE and Department of Experimental and Clinical;

    Immunoallergology Unit Department of BiomedicineCareggi University HospitalFlorence Italy;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 医学免疫学;
  • 关键词

    anti‐drug antibodies; hypersensitivity reactions; IgG4; infliximab;

    机译：抗药物抗体;过敏反应;IgG4;英夫利昔单抗;

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