肾移植后抗 SSA/SSB 抗体的 HLA 超敏狼疮肾炎患者接受亚胺立酶治疗对免疫球蛋白的影响:病例报告

IF 4.7 Q2 IMMUNOLOGY Journal of Translational Autoimmunity Pub Date : 2023-12-01 DOI:10.1016/j.jtauto.2023.100223
Jean Milhès , Olivier Marion , Benedicte Puissant , Caroline Carlé , Charlène Bouthemy , Arnaud Del Bello , Nassim Kamar , Yves Renaudineau , Nicolas Congy-Jolivet
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引用次数: 0

摘要

细菌重组半胱氨酸蛋白酶伊德斯(imlifidase,Idefirix®,Hansa Biopharma)用于预防高度 HLA 敏感受体的体液移植排斥反应,以及控制 IgG 介导的自身免疫性疾病。我们报告了一例患有狼疮性肾炎并伴有终末期肾病的 51 岁女性患者的病例。该患者为 HLA 过敏(计算的反应性抗体[Abs],cPRA>99 %),并有三种预形成的捐献者特异性抗体(DSA)。在开始治疗时(0、6、36、72 和 96 小时)以及注射伊立菲酶后一到两个月的抗体恢复期,对循环免疫球蛋白进行了监测。与基线相比,36 小时后总 IgG(-75%)和 IgG 亚类(IgG1、IgG2 和 IgG3 为-87%,IgG4 为-78%)的消耗较高,而 IgA 和 IgM 则无明显影响。注射伊立菲酶后,抗 SSA 60 kDa 和抗 SSB 自身抗体迅速下降(36 小时后两者均下降了 96%),疫苗接种后特异性 IgG 也迅速下降(36 小时后破伤风类毒素下降了 95%,肺炎球菌下降了 97%,流感嗜血杆菌抗体下降了 91%)。在抗体恢复阶段,总 IgG 和抗 SSA60/SSB 抗体在两个月后达到初始水平。至于同种异体反应性抗体,包括三种 DSA 在内的抗 HLA 抗体在注射后急剧下降,36 小时后从基线 100% 消减,这是由多重单珠抗原检测法评估的,使用淋巴细胞毒性(LCT)和流式细胞技术进行交叉配血均为阴性。恢复时 DSA 没有反弹,6 个月后仍低于阳性阈值(MFI = 1000)。本病例报告的研究结果表明,伊立菲酶对所有循环中的 IgG 均有早期消耗作用,而 IgG 的恢复可能部分取决于伊立菲酶靶向记忆 B 细胞的能力。
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Impact of imlifidase treatment on immunoglobulins in an HLA-hypersensitized lupus nephritis patient with anti-SSA/SSB antibodies after kidney transplantation: A case report

Bacterial recombinant cysteine protease Ides (imlifidase, Idefirix®, Hansa Biopharma) is used to prevent humoral transplant rejection in highly HLA-sensitized recipients, and to control IgG-mediated autoimmune diseases. We report the case of a 51 years old woman suffering from lupus nephritis with end stage kidney disease, grafted for the second time and pre-treated with imlifidase. The patient was HLA-hypersensitized (calculated Panel Reactive Antibodies [Abs], cPRA>99 %) and has three preformed Donor Specific Antibodies (DSA). Circulating immunoglobulins were monitored at initiation (0, 6, 36, 72 and 96 h), and at Ab recovery one and two months following imlifidase injection. From baseline, the higher depletion was reported after 36h for total IgG (−75 %) and IgG subclasses (−87 % for IgG1, IgG2 and IgG3, -78 % for IgG4), while no significant impact on IgA and IgM was observed. Anti-SSA 60 kDa and anti-SSB auto-Abs quickly decreased after imlifidase injection (−96 % for both after 36 h) as well as post-vaccinal specific IgG (−95 % for tetanus toxoid, −97 % for pneumococcus and −91 % for Haemophilus influenzae Abs after 36 h). At the Ab recovery phase, total IgG and anti-SSA60/SSB Abs reached their initial level at two months. Regarding alloreactive Abs, anti-HLA Abs including the three DSA showed a dramatic decrease after injection with 100 % depletion from baseline after 36 h as assessed by multiplex single bead antigen assay, leading to negative crossmatches using both lymphocytotoxicity (LCT) and flow cell techniques. DSA rebound at recovery was absent and remained under the positivity threshold (MFI = 1000) after 6 months. The findings from this case report are that imlifidase exerts an early depleting effect on all circulating IgG, while IgG recovery may depend in part from imlifidase's capacity to target memory B cells.

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来源期刊
Journal of Translational Autoimmunity
Journal of Translational Autoimmunity Medicine-Immunology and Allergy
CiteScore
7.80
自引率
2.60%
发文量
33
审稿时长
55 days
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