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Complement activity in myasthenia gravis is independent of autoantibody titer and disease severity.
medRxiv - Neurology Pub Date : 2021-01-20 , DOI: 10.1101/2021.01.15.21249875
Miriam L Fichtner , Michelle D Hoarty , Douangsone D Vadysirisack , Richard J Nowak , Kevin C. O'Connor

Acetylcholine receptor (AChR) autoantibodies, found in patients with autoimmune myasthenia gravis (MG), can directly contribute to disease pathology through activation of the classical complement pathway. Accordingly, complement inhibitors are used as a therapeutic strategy, but the response can be heterogeneous even though AChR autoantibodies are present. The mechanisms underlying the variable response are not defined. Yet there is a need for further understanding so that responses can be better predicted. There is a broad spectrum of circulating complement activity levels activity among MG patients. It is not clear whether this activity associates with disease burden or the circulating levels of autoantibodies. We measured complement activity and investigated these associations in MG patients as a means to explore candidate biomarkers. Most study subjects had complement activity within the range defined by healthy controls and no association between this activity and disease burden or AChR autoantibody titer was observed. Assays measuring the complement activating properties of AChR autoantibodies are needed to identifying patients expected to respond to complement inhibitor-based treatments.

中文翻译:

重症肌无力中的补体活性与自身抗体滴度和疾病严重性无关。

在患有自身免疫性重症肌无力(MG)的患者中发现的乙酰胆碱受体(AChR)自身抗体可通过激活经典补体途径直接促进疾病病理。因此,补体抑制剂被用作治疗策略,但是即使存在AChR自身抗体,反应也可能是异质的。没有定义变量响应的基础机制。然而,需要进一步理解,以便可以更好地预测响应。MG患者的循环补体活性水平活动范围广。目前尚不清楚这种活动是否与疾病负担或自身抗体的循环水平有关。我们测量了补体活性,并研究了MG患者中的这些关联,以探索候选生物标志物。大多数研究对象的补体活性处于健康对照定义的范围内,并且未观察到该活性与疾病负担或AChR自身抗体滴度之间的关联。需要测定AChR自身抗体的补体激活特性的测定方法,以鉴定预期对基于补体抑制剂的治疗产生反应的患者。
更新日期:2021-01-21
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