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病例报告:替雷利珠单抗致肺癌患者发生 THSD7A 阳性膜性肾病

Case Report: THSD7A-Positive Membranous Nephropathy Caused by Tislelizumab in a Lung Cancer Patient.

机构信息

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China.

Department of Nephrology, Peking Union Medical College Hospital, Beijing, China.

出版信息

Front Immunol. 2021 May 10;12:619147. doi: 10.3389/fimmu.2021.619147. eCollection 2021.

Abstract

Immune checkpoint inhibitors (ICIs) became the standard treatment for many different kinds of cancers and can result in a variety of immune-related adverse events (irAEs). IrAEs of kidney are uncommon and consists of different pathology types. Among the different types, membranous nephropathy (MN) is rare and have not been well-described. Since MN can also be associated with malignancies, differential diagnosis in patients receiving ICIs who develop MN can be very difficult. We present the case of a 74-year-old man with metastatic non-small cell lung cancer who developed MN after ICIs therapy. The patient tested positive for thrombospondin type-1 domain-containing 7A antibodies (THSD7A) when diagnosed with MN. Supplementary examinations revealed the predisposing antigen in the primary tumor and present of the antibody after immunotherapy, which corresponded to the patient's clinical course of nephropathy. Treatment consisting of systemic glucocorticoids and rituximab resulted in a good clinical response, and the THSD7A antibodies were no longer detected. In this case, we first discuss the potential mechanism of immunotherapy related MN, in which the activation of humoral immunity may play an important role.

摘要

免疫检查点抑制剂(ICIs)已成为许多不同类型癌症的标准治疗方法,并可导致多种免疫相关不良事件(irAEs)。肾脏的 irAEs 并不常见,包括不同的病理类型。在不同类型中,膜性肾病(MN)较为罕见,尚未得到充分描述。由于 MN 也可能与恶性肿瘤相关,因此在接受 ICI 治疗后发生 MN 的患者中进行鉴别诊断可能非常困难。我们报告了一例 74 岁患有转移性非小细胞肺癌的男性患者,在接受 ICI 治疗后发生 MN。该患者在诊断为 MN 时检测到血栓素 A1 型域包含 7A 抗体(THSD7A)阳性。辅助检查显示原发性肿瘤中的潜在抗原和免疫治疗后抗体的存在,与患者肾病的临床病程相对应。包括全身糖皮质激素和利妥昔单抗在内的治疗方案取得了良好的临床反应,并且不再检测到 THSD7A 抗体。在这种情况下,我们首先讨论了免疫治疗相关 MN 的潜在机制,其中体液免疫的激活可能发挥重要作用。

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