von Essen MR, Hellem MNN, Vinther-Jensen T, et al. - The authors estimated intrathecal cytokine synthesis and lymphocyte subsets in huntingtin (HTT) gene expansion carriers, gene expansion negative controls as a negative control group, and patients with primary progressive multiple sclerosis as a positive control group to investigate the possible contribution of an inflammatory response in Huntington disease (HD). Based on flow cytometry and enzyme-linked immunosorbent assays, lymphocyte activity in cerebrospinal fluid (CSF) from four cohorts of HTT gene expansion carriers (n = 121 in total) and controls was analyzed by techniques. Data from this study show immune abnormalities before the motor onset of disease. The authors observed increased levels of proinflammatory cytokines in CSF of HTT gene expansion carriers, including IL-17, and increased consumption of lymphocyte growth factor IL-7 before the motor onset of HD. Such results indicate that Th17.1 cells are involved in the earliest pathogenic phases of HD and propose that treatment to dampen T -cell–driven inflammation prior to motor onset could be of benefit in HTT gene expansion carriers.