Martin-Liberal Juan, Furness Andrew Js, Joshi Kroopa, Peggs Karl S, Quezada Sergio A, Larkin James
Renal and Melanoma Unit, The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK.
Cancer Immunol Immunother. 2015 Jun;64(6):765-7. doi: 10.1007/s00262-015-1689-1. Epub 2015 Apr 1.
The anti programmed cell death-1 (PD-1) antibodies pembrolizumab and nivolumab have been recently licensed by the Food and Drug Administration for the treatment of advanced melanoma. Immune checkpoint inhibitors such as these can induce endocrine adverse events but autoimmune diabetes has not been described to date. However, there is a strong preclinical rationale that supports this autoimmune toxicity. We describe for the first time the case of an adult patient who developed autoimmune diabetes likely as a consequence of PD-1 inhibition with pembrolizumab. The presence of high serum titres of anti-glutamic acid decarboxylase antibodies together with a suggestive clinical presentation, age of the patient and preclinical data strongly support an autoimmune aetiology of the diabetes. Moreover, the patient was found to have a well-known high-risk human leucocyte antigen type for the development of type 1 diabetes in children, so the PD-1 inhibition is very likely to have triggered the autoimmune phenomenon. Our case suggests that insulin-dependent diabetes might be a rare but important anti-PD-1 immune-related adverse event.
抗程序性细胞死亡蛋白1(PD-1)抗体帕博利珠单抗和纳武利尤单抗最近已获美国食品药品监督管理局批准用于治疗晚期黑色素瘤。这类免疫检查点抑制剂可诱发内分泌不良事件,但迄今为止尚未有自身免疫性糖尿病的相关报道。然而,有强有力的临床前理论依据支持这种自身免疫毒性。我们首次描述了一例成年患者,其发生自身免疫性糖尿病可能是帕博利珠单抗抑制PD-1的结果。高血清滴度的抗谷氨酸脱羧酶抗体的存在,连同提示性的临床表现、患者年龄及临床前数据,有力地支持了糖尿病的自身免疫病因。此外,该患者被发现具有儿童1型糖尿病发生时一种众所周知的高危人类白细胞抗原类型,因此PD-1抑制很可能触发了自身免疫现象。我们的病例提示,胰岛素依赖型糖尿病可能是一种罕见但重要的抗PD-1免疫相关不良事件。