D02 Associations Between Disease Stage And Levels Of Cytokines In Huntington's Disease

Abstract

Background Several studies have demonstrated increased levels of pro-inflammatory cytokines in the serum of HD mutation carriers compared with healthy controls. Aims To investigate the association between disease stage as reflected in Total Functional Capacity score and motor score on the one hand, and levels of pro-inflammatory and anti-inflammatory cytokines on the other hand in the serum of HD mutation carriers, both cross-sectionally and longitudinally. Method Blood samples suitable for determination of cytokine levels were withdrawn from a cohort initially comprising 152 HD mutation carriers and 54 healthy controls at two follow-up measurements with an average interval of 2 years. Global daily functioning was assessed using the Total Functional Capacity (TFC) scale and motor symptoms were assessed by trained neurologists using the motor section of the Unified Huntington’s Disease Rating Scale (UHDRS). Using multilevel regression analyses, cross-sectional associations between disease stage and levels of cytokines were assessed. Longitudinal changes in levels of cytokines were assessed using paired t-tests. Results Compared to controls, mutation carries did not differ in their cytokine level increase over time. The pro-inflammatory cytokines IL-6 and TNF-alpha were higher in motorsymptomatic mutation carriers compared with pre-motorsymptomatic mutation carriers. The anti-inflammatory cytokine IL-5 was lower in motorsymptomatic mutation carriers compared with pre-motorsymptomatic mutation carriers. IL-6 increases significantly across progressing disease reflected in TFC score. Conclusion We found evidence for increasing levels of pro-inflammatory cytokines across progressing disease. In addition, levels of anti-inflammatory cytokines may decrease in later disease stages.