自身免疫抗体在预测接受阿仑单抗治疗的复发缓解型多发性硬化患者继发自身免疫中的作用：一项全国性前瞻性调查。
The role of autoimmune antibodies to predict secondary autoimmunity in patients with relapsing-remitting multiple sclerosis treated with alemtuzumab: A nationwide prospective survey.
作者信息
Sandgren Sofia, Novakova Lenka, Axelsson Markus, Amirbeagi Firoozeh, Kockum Ingrid, Olsson Tomas, Malmestrom Clas, Lycke Jan
机构信息
Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Laboratory for Clinical Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
出版信息
Front Neurol. 2023 Mar 16;14:1137665. doi: 10.3389/fneur.2023.1137665. eCollection 2023.
BACKGROUND
Alemtuzumab (ALZ) is an immune reconstitution therapy for treating relapsing-remitting multiple sclerosis (RRMS). However, ALZ increases the risk of secondary autoimmune diseases (SADs).
OBJECTIVE
We explored whether the detection of autoimmune antibodies (auto-Abs) could predict the development of SADs.
METHODS
We included all patients with RRMS in Sweden who initiated ALZ treatment ( = 124, 74 female subjects) from 2009 to 2019. The presence of auto-Abs was determined in plasma samples obtained at the baseline and at 6, 12, and 24 months of follow-up, as well as in a subgroup of patients ( = 51), it was determined in plasma samples obtained at the remaining 3-month intervals up to 24 months. Monthly blood tests, urine tests, and the assessment of clinical symptoms were performed for monitoring safety including that of SADs.
RESULTS
Autoimmune thyroid disease (AITD) developed in 40% of patients, within a median follow-up of 4.5 years. Thyroid auto-Abs were detected in 62% of patients with AITD. The presence of thyrotropin receptor antibodies (TRAbs) at the baseline increased the risk of AITD by 50%. At 24 months, thyroid auto-Abs were detected in 27 patients, and 93% (25/27) developed AITD. Among patients without thyroid auto-Abs, only 30% (15/51) developed AITD ( < 0.0001). In the subgroup of patients ( = 51) with more frequent sampling for auto-Abs, 27 patients developed ALZ-induced AITD, and 19 of them had detectable thyroid auto-Abs prior to the AITD onset, with a median interval of 216 days. Eight patients (6.5%) developed non-thyroid SAD, and none had detectable non-thyroid auto-Abs.
CONCLUSION
We conclude that monitoring thyroid auto-Abs, essentially TRAbs, may improve the surveillance of AITD associated with ALZ treatment. The risk for non-thyroid SADs was low, and monitoring non-thyroid auto-Abs did not seem to provide any additional information for predicting non-thyroid SADs.
背景
阿仑单抗（ALZ）是一种用于治疗复发缓解型多发性硬化症（RRMS）的免疫重建疗法。然而，ALZ会增加继发自身免疫性疾病（SADs）的风险。
目的
我们探讨了自身抗体（自身抗体）检测是否能预测SADs的发生。
方法
我们纳入了2009年至2019年在瑞典开始接受ALZ治疗的所有RRMS患者（n = 124，74名女性受试者）。在基线以及随访的6个月、12个月和24个月时采集的血浆样本中测定自身抗体的存在情况，对于一个亚组患者（n = 51），在长达24个月的其余3个月间隔采集的血浆样本中也进行了测定。每月进行血液检查、尿液检查以及临床症状评估以监测安全性，包括SADs的安全性。
结果
在中位随访4.5年期间，40%的患者发生了自身免疫性甲状腺疾病（AITD）。在发生AITD的患者中，62%检测到甲状腺自身抗体。基线时促甲状腺素受体抗体（TRAbs）的存在使AITD的风险增加了50%。在24个月时，27名患者检测到甲状腺自身抗体，其中93%（25/27）发生了AITD。在没有甲状腺自身抗体的患者中，只有30%（15/51）发生了AITD（P < 0.0001）。在自身抗体采样更频繁的亚组患者（n = 51）中，27名患者发生了ALZ诱导的AITD，其中19名在AITD发病前检测到可检测的甲状腺自身抗体，中位间隔时间为216天。8名患者（6.5%）发生了非甲状腺SAD，且均未检测到可检测的非甲状腺自身抗体。
结论
我们得出结论，监测甲状腺自身抗体，主要是TRAbs，可能会改善与ALZ治疗相关的AITD的监测。非甲状腺SADs的风险较低，监测非甲状腺自身抗体似乎并未为预测非甲状腺SADs提供任何额外信息。
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