Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. We examined the peripheral immune system and found widespread evidence of innate immune activation detectable in plasma throughout the course of HD. Interleukin 6 levels were increased in HD gene carriers with a mean of 16 years before the predicted onset of clinical symptoms. To our knowledge, this is the earliest plasma abnormality identified in HD. Monocytes from HD subjects expressed mutant huntingtin and were pathologically hyperactive in response to stimulation, suggesting that the mutant protein triggers a cell-autonomous immune activation. A similar pattern was seen in macrophages and microglia from HD mouse models, and the cerebrospinal fluid and striatum of HD patients exhibited abnormal immune activation, suggesting that immune dysfunction plays a role in brain pathology. Collectively, our data suggest parallel central nervous system and peripheral pathogenic pathways of immune activation in HD.

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| 389 perhaps indicating that these cells reside in the mucosal tissue rather than the nasal lumen. These findings do not directly challenge previous studies performed in-season. Rather, they underscore the importance of considering ongoing chronic allergen exposure as an additional factor when assessing the role of immune cells in AR pathophysiology. ACKNOWLEDGMENTS We thank Matthew Gordon of Queen's University Biomedical ImagingCentre for his technical assistance with flow cytometry experiments. CONFLI CTS OF INTERES TS