Journal Article

C19 The immune response to the N-terminal human mutant huntingtin in minipig model

Ellederova, Zdenka, Kovarova, Hana, Motlik, Jan, Butalova, Nikola, Vochozkova, Petra, Valekova, Ivona

2016

Overview

BackgroundGiven evidence that mutated huntingtin is expressed in peripheral immune cells, it is possible that inflammatory changes detected in peripheral tissues may reflect the inflammatory process in CNS. Peripheral immune cells are collected by non-invasive approach which is easily feasible in patients. AimsThe objective of this observation was to identify alterations in molecules produced by peripheral immune cells and in serum in transgenic HD minipig model. MethodsA multiplex immunoassay (bead-based Luminex xMAP technology) was applied for the simultaneous determination of 7 cytokines in serum and in secretomes of myeloid cells (monocytes and macrophages). Additionally, an activity of different complement pathways was measured in serum by Wieslab®Complement system Screen kit. Age-matched TgHD and WT minipigs with similar genetic background and before the onset of clinical symptoms were used in this study. ResultsSerum level of IL-8 was found to be significantly increased in TgHD animals. It did not correlate with findings in monocyte secretomes where the IL-8 level oscillated. Measurements of cytokine level in macrophage secretomes showed raised production of IL-1β, IFNα and TNFα after cell stimulation in TgHD animals at the age of 48–56 months. Besides that, the complement test revealed a significantly increased activity of the classical pathway in serum from TgHD animals at the age of 24 and 36 months.ConclusionsThis study identified molecules animals which were altered in the periphery of TgHD. These molecules could serve as biomarkers for monitoring of organism response to treatment against mHTT effect in transgenic HD minipigs. SupportCHDI (A-8248, A-5378), EXAM (CZ.1.05/2.1.00/03.0124), National Sustainability Programme (LO1609), RVO67985904, GAUK No 378215