Myeloid-derived suppressor cells expansion is closely associated with disease severity and progression in HBV-related acute-on-chronic liver failure
JOURNAL OF MEDICAL VIROLOGY
Authors: Zeng, Yingfu; Li, Yiting; Xu, Zhen; Gan, Weiqiang; Lu, Lirong; Huang, Xiaohui; Lin, Chaoshuang
Dysregulation of the host immune responses induced by host hepatitis B virus (HBV) interactions has been observed in acute-on-chronic liver failure (ACLF). Myeloid-derived suppressor cells (MDSCs), well known for their immunomodulatory properties, can suppress T-cell function by regulating the expression of CD3 zeta chain in cancer and autoimmune/infectious diseases while rarely have been studied in ACLF. In this study, MDSCs, CD4(+)/CD8(+) T cells, and CD3 zeta chain were analyzed by flow cytometry in peripheral blood mononuclear cells obtained from HBV-related ACLF patients, chronic hepatitis B (CHB) patients and healthy controls. ACLF patients were followed up for dynamic detection of MDSCs and observation of outcomes after treatment. Interestingly, peripheral CD14(+)CD33(+)CD11b(+)HLA-DR-/low MDSCs from ACLF patients were significantly increased compared to those from CHB patients and healthy controls. CD4(+)/CD8(+) T cell frequency and CD3 zeta chain expression in T cells were decreased in ACLF patients compared to those of healthy controls and were negatively correlated with matched MDSC frequency. Meanwhile, the frequency of MDSCs was closely correlated with biochemical parameters that are relevant for liver injury rather than virological parameters. Moreover, a lower level of MDSCs was correlated with a better short-term prognosis (within 4 weeks but not at 8 weeks), and MDSCs remained high in ACLF patients whose conditions worsened within a 4-week follow-up period after treatment. These results suggest that MDSCs are closely involved in cell-mediated immunity in HBV-related ACLF and that peripheral MDSC expansion is closely associated with disease severity and progression in HBV-related ACLF, which may serve as a predictor of short-term prognosis.
Alzheimer's disease as a multistage process: an analysis from a population-based cohort study
Authors: Licher, Silvan; van der Willik, Kimberly D.; Vinke, Elisabeth J.; Yilmaz, Pinar; Fani, Lana; Schagen, Sanne B.; Ikram, M. Arfan; Ikram, M. Kamran
In cancer research, multistage models are used to assess the multistep process that leads to the onset of cancer. In view of biological and clinical similarities between cancer and dementia, we used these models to study Alzheimer's disease (AD). From the population-based Rotterdam Study, we included 9,362 non-demented participants, of whom 1,124 developed AD during up to 26 years of follow-up. Under a multistage model, we regressed the logarithm of AD incidence rate against the logarithm of five-year age categories. The slope in this model reflects the number of steps (n-1) required for disease onset before the final step leading to disease manifestation. A linear relationship between log incidence rate and log age was observed, with a slope of 12.82 (95% confidence interval: 9.01-16.62), equivalent to 14 steps. We observed fewer steps for those at high genetically determined risk: 12 steps for APOE-epsilon 4 carriers, and 10 steps for those at highest genetic risk based on APOE and a genetic risk score. The pathogenesis of AD complies with a multistage disease-model, requiring 14 steps before disease manifestation. Genetically predisposed individuals require fewer steps indicating that they already inherited multiple of these steps. Unravelling these steps in AD pathogenesis could benefit the development of intervention strategies.