抗IL-5美泊利单抗对重症哮喘患者残余血嗜酸性粒细胞有最低限度的影响
2021/09/24
摘要
抗白细胞介素（IL）-5的中和抗体已被广泛用于控制重症嗜酸性哮喘。值得注意的是，接受中和抗IL5生物疗法的患者保留了非常稳定的残余血嗜酸性粒细胞群。这些残留的嗜酸性粒细胞是否具有特定的生物活性尚未被研究，但对于预测IL5中和对患者的潜在长期影响具有重要意义。为了解决IL5缺失对残余嗜酸性粒细胞的影响，我们使用了比较RNA测序方法，并比较了在IL5缺失或IL5饱和的人类或小鼠宿主（在体内稳定状态下以及在体外用嗜酸性粒细胞激活蛋白IL33刺激后）中嗜酸性粒细胞生成的基因表达程序。我们比较了不同组别患者的血嗜酸性粒细胞，如接受抗IL5美泊利单抗治疗的重症过敏性嗜酸性哮喘患者，健康对照组及接受抗IgE-奥马珠单抗治疗的配对哮喘患者。我们对IL5基因缺陷与否的小鼠骨髓嗜酸性粒细胞进行了类似的比较。我们报告，在美泊利单抗治疗的患者或IL5缺陷小鼠中，限制IL5的可用性并没有在稳态残留嗜酸性粒细胞中引起任何可检测的转录反应，并且只影响了少数基因对IL33的反应。总之，这些结果支持了这样一种观点，即用IL5中和抗体治疗后，循环中仍有一些残留的嗜酸性粒细胞，这些嗜酸性粒细胞与健康人的嗜酸性粒细胞非常相似。
Anti-IL-5 mepolizumab minimally influences residual blood eosinophils in severe asthma
Glenn Van Hulst, Joseph Jorssen, Nathalie Jacobs, Monique Henket, Renaud Louis, Florence Schleich, Fabrice Bureau, Christophe J Desmet
Abstract
Neutralising antibodies against the cytokine interleukin (IL)-5 have become widely used for the control of severe eosinophilic asthma. Remarkably, patients receiving neutralising anti-IL5 biological therapies retain a very stable population of residual blood eosinophils. Whether these residual eosinophils are endowed with particular biological activity has not yet been studied but is of importance in predicting potential long-term effects of IL5 neutralisation in patients. To tackle the effect of IL5 depletion on residual eosinophils, we used a comparative RNA-sequencing approach and compared the gene expression program of eosinophils arising in IL5-depleted or IL5-replete human or murine hosts, at steady-state in vivo and following in vitro stimulation with the eosinophil-activating alarmin IL33. We compared blood eosinophils from patients with severe allergic eosinophilic asthma treated with anti-IL5 mepolizumab therapy to those of healthy controls and matched asthma patients receiving anti-IgE omalizumab therapy. We made similar comparisons on bone marrow eosinophils from mice genetically deficient or not for IL5. We report that restriction of IL5 availability did not elicit any detectable transcriptional response in steady-state residual eosinophils in mepolizumab-treated patients or IL5-deficient mice, and influenced only a handful of genes in their response to IL33. Together, these results support the notion that treatment with IL5 neutralising antibodies spares a pool of circulating residual eosinophils largely resembling those of healthy individuals.
抗白细胞介素（IL）-5的中和抗体已被广泛用于控制重症嗜酸性哮喘。值得注意的是，接受中和抗IL5生物疗法的患者保留了非常稳定的残余血嗜酸性粒细胞群。这些残留的嗜酸性粒细胞是否具有特定的生物活性尚未被研究，但对于预测IL5中和对患者的潜在长期影响具有重要意义。为了解决IL5缺失对残余嗜酸性粒细胞的影响，我们使用了比较RNA测序方法，并比较了在IL5缺失或IL5饱和的人类或小鼠宿主（在体内稳定状态下以及在体外用嗜酸性粒细胞激活蛋白IL33刺激后）中嗜酸性粒细胞生成的基因表达程序。我们比较了不同组别患者的血嗜酸性粒细胞，如接受抗IL5美泊利单抗治疗的重症过敏性嗜酸性哮喘患者，健康对照组及接受抗IgE-奥马珠单抗治疗的配对哮喘患者。我们对IL5基因缺陷与否的小鼠骨髓嗜酸性粒细胞进行了类似的比较。我们报告，在美泊利单抗治疗的患者或IL5缺陷小鼠中，限制IL5的可用性并没有在稳态残留嗜酸性粒细胞中引起任何可检测的转录反应，并且只影响了少数基因对IL33的反应。总之，这些结果支持了这样一种观点，即用IL5中和抗体治疗后，循环中仍有一些残留的嗜酸性粒细胞，这些嗜酸性粒细胞与健康人的嗜酸性粒细胞非常相似。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Eur Respir J.2021 Sep 2;2100935.doi: 10.1183/13993003.00935-2021.)
(Eur Respir J.2021 Sep 2;2100935.doi: 10.1183/13993003.00935-2021.)
Anti-IL-5 mepolizumab minimally influences residual blood eosinophils in severe asthma
Glenn Van Hulst, Joseph Jorssen, Nathalie Jacobs, Monique Henket, Renaud Louis, Florence Schleich, Fabrice Bureau, Christophe J Desmet
Abstract
Neutralising antibodies against the cytokine interleukin (IL)-5 have become widely used for the control of severe eosinophilic asthma. Remarkably, patients receiving neutralising anti-IL5 biological therapies retain a very stable population of residual blood eosinophils. Whether these residual eosinophils are endowed with particular biological activity has not yet been studied but is of importance in predicting potential long-term effects of IL5 neutralisation in patients. To tackle the effect of IL5 depletion on residual eosinophils, we used a comparative RNA-sequencing approach and compared the gene expression program of eosinophils arising in IL5-depleted or IL5-replete human or murine hosts, at steady-state in vivo and following in vitro stimulation with the eosinophil-activating alarmin IL33. We compared blood eosinophils from patients with severe allergic eosinophilic asthma treated with anti-IL5 mepolizumab therapy to those of healthy controls and matched asthma patients receiving anti-IgE omalizumab therapy. We made similar comparisons on bone marrow eosinophils from mice genetically deficient or not for IL5. We report that restriction of IL5 availability did not elicit any detectable transcriptional response in steady-state residual eosinophils in mepolizumab-treated patients or IL5-deficient mice, and influenced only a handful of genes in their response to IL33. Together, these results support the notion that treatment with IL5 neutralising antibodies spares a pool of circulating residual eosinophils largely resembling those of healthy individuals.
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