布氏布氏锥虫所致人类非洲锥虫病猴子模型中的IgM、IgG和白细胞介素-6情况

IgM, lgG and IL-6 profiles in the Trypanosoma brucei brucei monkey model of human African trypanosomiasis.

作者信息

Waema Maxwell W, Maina Naomi W, Ngotho Maina, Karanja Simon M, Gachie Beatrice M, Maranga Dawn N, Kagira John M

机构信息

Jomo Kenyatta University of Agriculture and Technology, College of Health Sciences, Biochemistry Department, P.O. Box 62000-00200, Nairobi, Kenya.

Mount Kenya University, Department of Animal Health and Production, P.O. Box 342-01000,Thika, Kenya; Jomo Kenyatta University of Agriculture and Technology, College of Agriculture and Natural Resources, Animal Sciences Department, P.O. Box 62000-00200, Nairobi, Kenya.

出版信息

Acta Trop. 2017 Apr;168:45-49. doi: 10.1016/j.actatropica.2017.01.012. Epub 2017 Jan 15.

DOI:10.1016/j.actatropica.2017.01.012

PMID:28099874

Abstract

Human African trypanosomiasis (HAT) patients manifest immunological profiles, whose variations over time can be used to indicate disease progression. However, monitoring of these biomarkers in human patients is beset by several limitations which can be offset by using chronic animal models. A recent improved monkey model of HAT using a Trypanosoma brucei brucei isolate has been developed but the immunological profile has not been elucidated. The objectives of the current study was to determine the IgM, IgG and IL-6 profiles in blood and cerebrospinal fluid (CSF) in vervet monkeys infected with T. b. brucei. Three vervet monkeys were infected intravenously with 10T. b. brucei, monitored for disease development and subsequently treated 28days post infection (dpi) sub-curatively using diminazene aceturate (DA) to induce late stage disease and curatively treated with melarsoprol (Mel B) at 119 dpi, respectively. Matched serum and cerebrospinal fluid (CSF) samples were obtained at regular intervals and immunospecific IgM, immunoglobulin G (IgG) were quantified by ELISA while IL-6 was assayed using a cytometric bead array (CBA) kit. Results showed that following infection, CSF IgM, IgG, IL-6 and serum IL-6 were significantly (p<0.05) elevated with peak levels coinciding with relapse parasitaemia. The IgG levels increased to reach OD peak levels of 0.442±0.5 at 126 dpi. After curative treatment with MelB, the serum IgM and Ig G levels fell rapidly to attain pre-infection levels within 35 and 49days, respectively. This shows that the profile of these immunoglobulins can be used as an indicator of curative treatment. CSF IL-6 concentrations of infected vervet monkeys showed no significant change (P>0.05) between infection and 35 dpi but levels increased significantly (P<0.05) with the highest level of 55.53pg/ml recorded at112 dpi. IL-6 elevation from 35 dpi may be indicative of parasite neuroinvasion hence can be used as possible candidate marker for late stage disease in the monkey model. Further, the marker can also be used in conjunction with IgG and IgM as markers for development of test of cure for HAT.

摘要

人类非洲锥虫病（HAT）患者呈现出免疫特征，其随时间的变化可用于指示疾病进展。然而，在人类患者中监测这些生物标志物存在若干局限性，而使用慢性动物模型可以弥补这些局限性。最近开发了一种使用布氏布氏锥虫分离株的改良HAT猴模型，但尚未阐明其免疫特征。本研究的目的是确定感染布氏布氏锥虫的黑长尾猴血液和脑脊液（CSF）中的IgM、IgG和IL-6特征。三只黑长尾猴静脉注射10个布氏布氏锥虫，监测疾病发展，随后在感染后28天（dpi）分别使用乙酰氨基阿苯（DA）进行次治愈性治疗以诱导晚期疾病，并在119 dpi时使用美拉胂醇（Mel B）进行治愈性治疗。定期采集匹配的血清和脑脊液（CSF）样本，通过ELISA定量免疫特异性IgM、免疫球蛋白G（IgG），同时使用细胞计数珠阵列（CBA）试剂盒检测IL-6。结果显示，感染后，CSF IgM、IgG、IL-6和血清IL-6显著升高（p<0.05），峰值水平与复发寄生虫血症一致。IgG水平在126 dpi时增加至OD峰值水平0.442±0.5。用MelB进行治愈性治疗后，血清IgM和IgG水平迅速下降，分别在35天和49天内达到感染前水平。这表明这些免疫球蛋白的特征可作为治愈性治疗的指标。感染黑长尾猴的CSF IL-6浓度在感染至35 dpi之间无显著变化（P>0.05），但水平显著升高（P<0.05），在112 dpi时记录到最高水平55.53pg/ml。35 dpi后IL-6升高可能表明寄生虫神经侵袭，因此可作为猴模型中晚期疾病的可能候选标志物。此外，该标志物还可与IgG和IgM联合用作HAT治愈检测发展的标志物。