Anaphylaxis and mortality induced by treatment of mice with anti-VLA-4 antibody and pertussis toxin.
Anaphylaxis and mortality induced by treatment of mice with anti-VLA-4 antibody and pertussis toxin.
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DOI：
10.4049/jimmunol.1000907
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发表时间：
2011-03-01
期刊：
影响因子：
--
通讯作者：
Forsthuber TG
中科院分区：
文献类型：
--
作者：
Ji N;Rao N;Guentzel NM;Arulanandam BP;Forsthuber TG
抗体介导的粘附分子极晚期抗原-4（VLA-4）的阻断已显示可改善人类多发性硬化症（MS）患者和实验性自身免疫性脑脊髓炎（EAE）动物模型的疾病。我们想确定抗VLA-4抗体治疗是否影响EAE小鼠自身反应性T细胞的功能和持久性。出乎意料的是，我们在抗VLA-4 mAb（PS/2）治疗的患有主动诱导的EAE的小鼠中观察到高水平的死亡率，尽管疾病严重程度降低。对潜在机制的研究表明，PS/2 mAb与百日咳毒素（PTX）联合注射导致过敏反应和死亡。此外，数据显示，这种效应需要CD 4 + T细胞，并表明IL-1β和TNF-α在基础病理学中的作用。结果揭示了抗VLA-4抗体治疗与暴露于PTX组合的先前未被认识到的有害作用。
Antibody-mediated blockade of the adhesion molecule very late antigen-4 (VLA-4) has been shown to ameliorate disease in human multiple sclerosis (MS) patients and experimental autoimmune encephalomyelitis (EAE) animal models. We wanted to determine whether anti-VLA-4 antibody treatment affected the function and persistence of autoreactive T cells in mice with EAE. Unexpectedly, we observed a high level of mortality in anti-VLA-4 mAb (PS/2) treated mice with actively induced EAE despite decreased disease severity. Investigation of the underlying mechanism showed that injection of PS/2 mAb in combination with pertussis toxin (PTX) resulted in anaphylaxis and mortality. Furthermore, the data showed that CD4+ T cells were required for this effect and suggested a role for IL-1β and TNF-α in the underlying pathology. The results reveal a previously not appreciated deleterious effect of anti-VLA-4 antibody treatment in combination with exposure to PTX.
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