Iverson William O, Karanth Subramanya, Wilcox Angela, Pham Cau D, Lockhart Shawn R, Nicholson Simone M
1 MedImmune LLC, One MedImmune Way, Gaithersburg, MD, USA.
2 Charles River Laboratories, Preclinical Services, Nevada, Reno, NV, USA.
Vet Pathol. 2018 Jul;55(4):591-594. doi: 10.1177/0300985818758468. Epub 2018 Feb 14.
A sexually mature Chinese-origin female Macaca fascicularis assigned to the high-dose group in a 26-week toxicology study with an experimental immunomodulatory therapeutic antibody (a CD40 L antagonist fusion protein) was euthanized at the scheduled terminal sacrifice on study day 192. The animal was healthy at study initiation and remained clinically normal throughout the study. On study day 141, abnormal clinical pathology changes were found during a scheduled evaluation; splenomegaly was detected on study day 149 and supported by ultrasound examination. At the scheduled necropsy, there was marked splenomegaly with a nodular and discolored appearance. Cytologic examination of a splenic impression smear revealed yeast-like organisms within macrophages. Histologically, there was disseminated systemic granulomatous inflammation with 2- to 3-μm oval, intracytoplasmic yeast-like organisms in multiple organs identified as Talaromyces (Penicillium) marneffei. This organism, not previously reported as a pathogen in macaques, causes an important opportunistic infection in immunosuppressed humans in specific global geographic locations.
在一项为期26周的毒理学研究中,一只性成熟的中国来源雌性食蟹猴被分配到高剂量组,该研究使用了一种实验性免疫调节治疗性抗体(一种CD40 L拮抗剂融合蛋白),在研究第192天按计划进行终末处死。该动物在研究开始时健康,并且在整个研究过程中临床状态正常。在研究第141天的一次计划评估中发现了异常的临床病理学变化;在研究第149天检测到脾肿大,并通过超声检查得到证实。在计划的尸检中,脾脏明显肿大,呈结节状且颜色异常。脾脏印片涂片的细胞学检查显示巨噬细胞内有酵母样生物体。组织学检查发现,多个器官出现弥漫性全身性肉芽肿性炎症,有2至3微米的椭圆形胞浆内酵母样生物体,鉴定为马尔尼菲篮状菌(青霉菌)。这种生物体以前未被报道为猕猴的病原体,在特定的全球地理位置,它会在免疫抑制的人类中引起重要的机会性感染。