Efficacy of Polyvalent Human Immunoglobulins in an Animal Model of Neuromyelitis Optica Evoked by Intrathecal Anti-Aquaporin 4 Antibodies
Efficacy of Polyvalent Human Immunoglobulins in an Animal Model of Neuromyelitis Optica Evoked by Intrathecal Anti-Aquaporin 4 Antibodies
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DOI：
10.3390/ijms17091407
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发表时间：
2016-09-01
影响因子：
5.6
通讯作者：
Geis, Christian
中科院分区：
文献类型：
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作者：
Gruenewald, Benedikt;Bennett, Jeffrey L.;Geis, Christian
视神经肌病谱系障碍（NMOSD）与靶向星形胶质细胞水通道蛋白-4水通道（AQP 4-AB）的自身抗体（AB）相关。这些AB通过在疾病过程中启动各种免疫和炎症过程而具有直接致病作用。在最近建立的动物模型中，NMOSD患者免疫球蛋白G（NMO-IgG）或重组人AQP 4-AB（rAB-AQP 4）的慢性鞘内被动转移为AQP 4-AB的互补和免疫细胞非依赖性作用提供了证据。利用这种动物模型，我们在这里测试的影响，全身和鞘内应用汇集人免疫球蛋白（IVIg）使用预防和治疗的范例。在NMO-IgG动物中，预防性应用全身IVIg导致0-10量表上的中位疾病评分降低至2.4，而假治疗为4.1。在第10次鞘内注射NMO-IgG后全身应用治疗性IVIg，使疾病评分显著降低0.8。鞘内IVIg应用在具有NMO-IgG（IVIg中位评分1.6 vs.假手术3.7）或具有rAB-AQP 4（IVIg中位评分2.0 vs.假手术3.7）的动物中诱导有益作用。我们在这里提供的证据表明，在这种被动转移模型中，IVIg治疗可改善疾病症状，这与以前研究其他抗体介导疾病的被动转移动物模型类似。
Neuromyelitis Optica Spectrum Disorders (NMOSD) are associated with autoantibodies (ABs) targeting the astrocytic aquaporin-4 water channels (AQP4-ABs). These ABs have a direct pathogenic role by initiating a variety of immunological and inflammatory processes in the course of disease. In a recently-established animal model, chronic intrathecal passive-transfer of immunoglobulin G from NMOSD patients (NMO-IgG), or of recombinant human AQP4-ABs (rAB-AQP4), provided evidence for complementary and immune-cell independent effects of AQP4-ABs. Utilizing this animal model, we here tested the effects of systemically and intrathecally applied pooled human immunoglobulins (IVIg) using a preventive and a therapeutic paradigm. In NMO-IgG animals, prophylactic application of systemic IVIg led to a reduced median disease score of 2.4 on a 0-10 scale, in comparison to 4.1 with sham treatment. Therapeutic IVIg, applied systemically after the 10th intrathecal NMO-IgG injection, significantly reduced the disease score by 0.8. Intrathecal IVIg application induced a beneficial effect in animals with NMO-IgG (median score IVIg 1.6 vs. sham 3.7) or with rAB-AQP4 (median score IVIg 2.0 vs. sham 3.7). We here provide evidence that treatment with IVIg ameliorates disease symptoms in this passive-transfer model, in analogy to former studies investigating passive-transfer animal models of other antibody-mediated disorders.