Objective

To evaluate whether serum matrix metallopeptidase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels predict response to adrenocorticotropic hormone (ACTH) therapy in patients with infantile spasms.

Methods

We prospectively evaluated patients with infantile spasms who were referred to Saitama Children’s Medical Center from January 2011 to December 2020. We measured Q-albumin and serum MMP-9 and TIMP-1 levels before ACTH therapy. Patients were divided into three groups based on the etiology of their infantile spasms: those with an unknown etiology and normal development (unknown-normal group); those with a structural and acquired etiology (structural-acquired group); and those with a structural and congenital, genetic, metabolic, or unknown etiology with developmental delay (combined-congenital group). Responders were defined as those having complete cessation of spasms for more than 3 months with the resolution of hypsarrhythmia on electroencephalography during ACTH therapy.

Results

We collected serum from 36 patients with West syndrome and five patients with infantile spasms without hypsarrhythmia before ACTH therapy. Twenty-three of 41 patients (56.1%) were responders, including 8/8 (100%) in the unknown-normal group, 6/9 (66.7%) in the structural-acquired group, and 9/24 (37.5%) in the combined-congenital group. The serum MMP-9 level and MMP-9/TIMP-1 ratio were significantly higher in responders than in nonresponders (P = 0.001 for both).

Conclusion

A therapeutic response to ACTH was associated with a higher serum MMP-9 level and higher MMP-9/TIMP-1 ratio in patients with infantile spasms. Therefore, these biomarkers may predict responses to ACTH therapy in this patient population.

中文翻译：

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血清基质金属肽酶 9 和金属蛋白酶组织抑制剂 1 水平可预测婴儿痉挛患者对促肾上腺皮质激素治疗的反应

客观的

评估血清基质金属肽酶 9 (MMP-9) 和金属蛋白酶组织抑制剂 1 (TIMP-1) 水平是否可预测婴儿痉挛患者对促肾上腺皮质激素 (ACTH) 治疗的反应。

方法

我们前瞻性评估了 2011 年 1 月至 2020 年 12 月转诊至埼玉儿童医疗中心的婴儿痉挛患者。我们在 ACTH 治疗前测量了 Q-白蛋白和血清 MMP-9 和 TIMP-1 水平。根据婴儿痉挛的病因将患者分为三组：病因不明且发育正常的患者（未知-正常组）；具有结构性和获得性病因的人（结构获得性组）；以及具有发育迟缓的结构性和先天性、遗传性、代谢性或病因不明的患者（先天性组合）。反应者定义为痉挛完全停止超过 3 个月，在 ACTH 治疗期间脑电图显示高节律失常消退。

结果

我们在 ACTH 治疗前收集了 36 名 West 综合征患者和 5 名无高节律失常的婴儿痉挛患者的血清。41 例患者中有 23 例（56.1%）有反应，其中未知正常组 8/8（100%），结构获得组 6/9（66.7%）和 9/24（37.5%）在先天性联合组。应答者的血清 MMP-9 水平和 MMP-9/TIMP-1 比值显着高于无应答者（两者P  = 0.001）。

结论

在婴儿痉挛症患者中，对 ACTH 的治疗反应与较高的血清 MMP-9 水平和较高的 MMP-9/TIMP-1 比率相关。因此，这些生物标志物可以预测该患者群体对 ACTH 治疗的反应。