Anakinra-Associated Systemic Amyloidosis.
Anakinra-Associated Systemic Amyloidosis.
复制标题
阿那白滞素相关的系统性淀粉样变性。
DOI：
10.1002/art.42664
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Chang,
中科院分区：
文献类型：
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作者：
Alehashemi,Sara;Dasari,Surendra;Metpally,Anvitha;Uss,Kat;Castelo-Soccio,LeslieA;Heller,Theo;Kellman,Peter;Chen,MarcusY;Ahlman,Mark;Kim,Jeff;Wargo,Susannah;Kuhns,DouglasB;Fink,Danielle;deJesus,Adriana;Martin,PaulS;Chang,
目的描述一名有新生儿发病多系统炎性疾病病史的41岁女性，自28岁起每天皮下注射600 mg重组白细胞介素-1受体拮抗剂（IL-1Ra）蛋白（阿那白滞素）治疗，在阿那白滞素注射部位出现高尔夫球大小的结节，早饱，在正常的系统性炎症标记物的背景下新发肾病综合征。方法皮肤，胃粘膜，用刚果红染色和液相色谱-串联质谱法对显微切割的刚果红阳性淀粉样蛋白沉积物进行蛋白质组学评价。肾活检都显示存在刚果红阳性淀粉样沉积物。基于质谱的蛋白质组学证明，所有部位的淀粉样蛋白沉积均为AIL1RAP（IL-1 Ra蛋白）型。其特征在于淀粉样蛋白特征蛋白（载脂蛋白AIV、载脂蛋白E和血清淀粉样蛋白P组分）和淀粉样蛋白生成IL-1 Ra蛋白的高光谱计数，这些蛋白存在于刚果红色阳性区域，而在刚果红色阴性区域不存在。氨基酸序列分析证实，该淀粉样前体蛋白为重组IL-1Ra（阿那白滞素），而非内源性野生型IL-1Ra。结论本研究首次报道了由重组IL-1Ra（阿那白滞素）引起的注射性蛋白药物所致的医源性系统性淀粉样变。
ObjectiveTo describe a 41‐year‐old woman with a history of neonatal onset multisystem inflammatory disease, on treatment with daily subcutaneous injections of 600 mg of recombinant interleukin‐1 receptor antagonist (IL‐1Ra) protein, anakinra, since the age of 28, who presented with golf‐ball size nodules at the anakinra injection sites, early satiety, new onset nephrotic syndrome in the context of normal markers of systemic inflammation.MethodsClinical history and histologic evaluation of biopsies of skin, gastric mucosa, and kidney with Congo‐red staining and proteomic evaluation of microdissected Congo red–positive amyloid deposits by liquid chromatography‐tandem mass spectrometry.ResultsThe skin, stomach, and kidney biopsies all showed the presence of Congo red–positive amyloid deposits. Mass spectrometry‐based proteomics demonstrated that the amyloid deposits in all sites were of AIL1RAP (IL‐1Ra protein)‐type. These were characterized by high spectral counts of the amyloid signature proteins (apolipoprotein AIV, apolipoprotein E, and serum amyloid P‐component) and the amyloidogenic IL‐1Ra protein, which were present in Congo red–positive areas and absent in Congo red–negative areas. The amino acid sequence identified by mass spectrometry confirmed that the amyloid precursor protein was recombinant IL‐1Ra (anakinra) and not endogenous wild‐type IL‐1Ra.ConclusionThis is the first report of iatrogenic systemic amyloidosis due to an injectable protein drug, which was caused by recombinant IL1Ra (anakinra).