A BS TRACT: Background: Despite extensive research regarding the etiology of Huntington's disease, relatively little is known about the epidemiology of this rare disorder, particularly in the United States where there are no national-scale estimates of the disease. Objectives: To provide national-scale estimates of Huntington's disease in a U.S. population and to test whether disease rates are increasing, and whether frequency varies by race, ethnicity, or other factors. Methods: Using an insurance database of over 67 million enrollees, we retrospectively identified a cohort of 3,707 individuals diagnosed with Huntington's disease between 2003 and 2016. We estimated annual incidence, annual diagnostic frequency, and tested for trends over time and differences in diagnostic frequency by sociodemographic characteristics. Results: During the observation period, the age-adjusted cumulative incidence rate was1.22 per 100,000 persons (95% confidence interval: 1.53, 1.65), and age-adjusted diagnostic frequency was 6.52 per 100,000 persons (95% confidence interval: 5.31, 5.66); both rates remained relatively stable over the 14-year period. We identified several previously unreported differences in Huntington's disease frequency by selfreported sex, income, and race/ethnicity. However, racial/ ethnic differences were of lower magnitude than have previously been reported in other country-level studies. Conclusions: In these large-scale estimates of U.S. Huntington's disease epidemiology, we found stable disease frequency rates that varied by several sociodemographic factors. These findings suggest that disease patterns may be more driven by social or environmental factors than has previously been appreciated. Results further demonstrate the potential utility of administrative Big Data in rare disease epidemiology when other data sources are unavailable.

BackgroundT helper (Th) 17 and regulatory T (Treg) cells play a critical role in the pathogenesis of multiple sclerosis (MS) disease. Bu Shen Yi Sui Capsule (BSYSC), a traditional Chinese medicine formula, has been used clinically for the treatment of MS patients in China.MethodsTo evaluate the neuroprotective effects and the underlying mechanisms of BSYSC on MS, experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice was induced with myelin oligodendrocyte glycoprotein (MOG) 35–55. Th17 and Treg cells and the related cytokines were detected by flow cytometry, ELISA, real-time quantitative reverse transcription PCR, western blot and immunohistochemistry.ResultsWe found that BSYSC improved neurological function, reduced inflammatory cell infiltration and damage to the axons and myelin in the brain and spinal cord. BSYSC down-regulated markedly the ratio of CD4 + IL-17+/CD4 + CD25 + FoxP3+ T cells in the spleen, decreased the cytokines of IL-17A, IL-6, IL-23, TGF-beta1 in the brain, and dropped the ratio of IL-17A and FoxP3 mRNA and protein in the brain or spinal cord at different stages.ConclusionsThe study demonstrated that BSYSC had a strong neuroprotective effect on EAE mice. The protective mechanisms of BSYSC might be associated with mediating the regulation of Th17/Treg cells.

BackgroundRemote ischemic preconditioning (RIPC) of a limb has been reported to protect against ischemic stroke. Our previous results demonstrated that the RIPC-mediated neuroprotection is associated with alterations in circulating immune cell populations. Here, we evaluated the effect of the spleen, the largest reservoir of immune cells, on RIPC-mediated neuroprotection against stroke.MethodsNoninvasive RIPC was achieved by four repeated cycles of 5-min blood flow constriction in the hindlimbs using a tourniquet. The blood and spleens were collected before and 1 h and 3 days after preconditioning to analyze the effect of RIPC on the spleen and the correlation between splenic and peripheral lymphocytes. Moreover, spleen weight and splenic lymphocytes were compared in stroke rats with or without RIPC. Finally, splenectomy was made 1 day or 2 weeks before RIPC and 90-min middle cerebral artery occlusion (MCAO). The infarct areas and deficits were assessed. Blood was collected 1 h after RIPC and 3 days after MCAO to explore the impact of splenectomy on RIPC-induced neuroprotection and immune changes. The contralateral and ipsilateral hemispheres were collected 3 days after MCAO to detect the infiltration of immune cells after RIPC and splenectomy.ResultsFlow cytometry analysis demonstrated that the RIPC promptly increased the percentages of CD3+CD8+ cytotoxic T (Tc) cells in the spleen with a relatively delayed elevation in CD3+CD161+ natural killer T (NKT) and CD3−CD45RA+ B lymphocytes. The percentages of circulating lymphocytes are positively correlated with the percentages of splenic lymphocytes in normal rats. Interestingly, RIPC resulted in negative correlations between the percentages of splenic and circulating T lymphocytes, while the correlation between splenic and circulating B lymphocytes remained positive. For animals subjected to RIPC followed by MCAO, RIPC increased splenic volume with an expansion of splenic lymphocytes 3 days after MCAO. Furthermore, the removal of the spleen 1 day or 2 weeks before RIPC and MCAO reduced the protective effect of RIPC on ischemic brain injury and reversed the effects of RIPC on circulating immune cell composition. RIPC significantly reduced brain infiltration of Tc and NKT cells. Prior splenectomy showed no effect on immune cell infiltration after RIPC and stroke.ConclusionThese results reveal an immunomodulatory effect of the spleen, effecting mainly the spleen-derived lymphocytes, during RIPC-afforded neuroprotection against cerebral ischemia.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1190-9) contains supplementary material, which is available to authorized users.

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