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The potential impact of timing of IVIG administration on the efficacy of rituximab for immune tolerance induction for patients with Pompe disease.
Clinical Immunology ( IF 4.5 ) Pub Date : 2020-07-15 , DOI: 10.1016/j.clim.2020.108541
Ankit K Desai 1 , Amy S Rosenberg 2 , Priya S Kishnani 1
Affiliation  

Immune modulation with rituximab, methotrexate, and intravenous immunoglobulin (IVIG) has shown great success in inducing immune tolerance in a large cohort of enzyme replacement therapy (ERT)-naïve infantile Pompe disease patients. Antibody-dependent cellular cytotoxicity, the principal mechanism by which rituximab depletes B-cells, requires CD20 binding by Fab’2 of rituximab on B-cells and the concomitant binding of its Fc region to Fc receptors on effector cells or to complement. To protect patients against microbial infections when using rituximab, IVIG was added to the immunomodulation regimen used in Pompe disease. Administration of IVIG can saturate neonatal Fc receptors (FcRn), which recycle endogenous as well as administered polyclonal/monoclonal antibodies via the binding of the Fc moiety to FcRn. As such, the administration of IVIG prior to rituximab, a chimeric mouse-human monoclonal antibody, may sharply reduce the half-life of rituximab and in turn, its efficacy. Based on this understanding, it is vital to understand the optimal timing of IVIG administration in relation to rituximab administration for the purposes of inducing immune tolerance.



中文翻译:

IVIG给药时间可能对利妥昔单抗对庞贝病患者的免疫耐受诱导的功效产生潜在影响。

利妥昔单抗,甲氨蝶呤和静脉注射免疫球蛋白(IVIG)的免疫调节已在一大批未使用过酶替代疗法(ERT)的婴儿期庞贝病患者中诱导免疫耐受方面取得了巨大成功。抗体依赖性细胞毒性是利妥昔单抗消耗B细胞的主要机制,需要利妥昔单抗的Fab'2将CD20结合到B细胞上,并伴随其Fc区与效应细胞或补体上的Fc受体结合。为了保护患者在使用利妥昔单抗时免受微生物感染,在庞贝病中使用的免疫调节方案中加入了IVIG。IVIG的给药可以使新生儿的Fc受体(FcRn)饱和,该受体会通过Fc部分与FcRn的结合而回收内源性以及给药的多克隆/单克隆抗体。因此,在嵌合的小鼠人单克隆抗体利妥昔单抗之前进行IVIG给药可能会急剧降低利妥昔单抗的半衰期,进而降低其功效。基于这种理解,至关重要的是要了解与利妥昔单抗给药有关的IVIG给药最佳时机,以诱导免疫耐受。

更新日期:2020-08-12
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