Comparison of Monocyte Gene Expression Among Patients with Neurocysticercosis-Associated Epilepsy, Idiopathic Epilepsy and Idiopathic Headaches in India

Citation: Prabhakaran V, Drevets DA, Ramajayam G, Manoj JJ, Anderson MP, Hanas JS, et al. (2017) Comparison of monocyte gene expression among patients with neurocysticercosis-associated epilepsy, Idiopathic Epilepsy and idiopathic headaches in India. PLoS Negl Trop Dis 11(6): e0005664. https://doi.org/10.1371/journal.pntd.0005664
Published: June 16, 2017

Abstract
Background: Neurocysticercosis (NCC), a neglected tropical disease, inflicts substantial health and economic costs on people living in endemic areas such as India. Nevertheless, accurate diagnosis using brain imaging remains poorly accessible and too costly in endemic countries. The goal of this study was to test if blood monocyte gene expression could distinguish patients with NCC-associated epilepsy, from NCC-negative imaging lesion-free patients presenting with idiopathic epilepsy or idiopathic headaches.
Methods/Principal findings: Patients aged 18 to 51 were recruited from the Department of Neurological Sciences, Christian Medical College and Hospital, Vellore, India, between January 2013 and October 2014. mRNA from CD14+ blood monocytes was isolated from 76 patients with NCC, 10 Recovered NCC (RNCC), 29 idiopathic epilepsy and 17 idiopathic headaches patients. A preliminary microarray analysis was performed on six NCC, six idiopathic epilepsy and four idiopathic headaches patients to identify genes differentially expressed in NCC-associated epilepsy compared with other groups. This analysis identified 1411 upregulated and 733 downregulated genes in patients with NCC compared to Idiopathic Epilepsy. Fifteen genes up-regulated in NCC patients compared with other groups were selected based on possible relevance to NCC, and analyzed by qPCR in all patients’ samples. Differential gene expression among patients was assessed using linear regression models. qPCR analysis of 15 selected genes showed generally higher gene expression among NCC patients, followed by RNCC, idiopathic headaches and Idiopathic Epilepsy. Gene expression was also generally higher among NCC patients with single cyst granulomas, followed by mixed lesions and single calcifications.
Conclusions/Significance: Expression of certain genes in blood monocytes can distinguish patients with NCC-related epilepsy from patients with active Idiopathic Epilepsy and idiopathic headaches. These findings are significant because they may lead to the development of new tools to screen for and monitor NCC patients without brain imaging.

Author summary: Taenia solium is a parasite normally transmitted between humans and pigs in areas with poor sanitation. Neurocysticercosis (NCC) occurs when humans are infected with larvae of T. solium that are shed with human feces and the larvae establish in the brain. NCC is often accompanied by neurological symptoms such as epilepsy. In fact, NCC causes approximately one-third of epilepsy cases in areas where T. solium is common. Unfortunately, diagnosis of NCC requires brain computerized tomography or magnetic resonance imaging, tools rarely accessible to people living where NCC is prevalent. This study tested whether genes expressed in blood monocytes, a type of white blood cell, could distinguish between people with epilepsy caused by NCC from those with epilepsy of unknown cause (idiopathic). We compared gene expression in people with NCC and epilepsy, people with idiopathic epilepsy, people cured of NCC and people without NCC or epilepsy but with headaches. We identified 15 genes which were expressed differently in the four different groups indicating that monocyte gene expression patterns in people with NCC and epilepsy are different than people with idiopathic epilepsy. These findings could lead to better understanding how humans respond to NCC and to diagnostic tests which would not require brain imaging.

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