Processing speed is related to striatal dopamine transporter availability in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) affects the integrity of the dopamine and serotonin system, and is characterized by a plethora of different symptoms, including cognitive impairments of which the pathophysiology is not yet fully elucidated. OBJECTIVES: Investigate the role of the integrity of the dopaminergic and serotonergic system in cognitive functioning in early-stage PD using Single Photon Emission Computed Tomography (SPECT) combined with the radiotracer 123I-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane (123I-FP-CIT). METHODS: We studied the association between cognitive functions and dopamine transporter (DAT) availability in the caudate nucleus and putamen - as a proxy for striatal dopaminergic integrity - and serotonin transporter (SERT) availability as a proxy for serotonergic integrity in the thalamus and hippocampus using bootstrapped multiple regression. One-hundred-and-twenty-nine (129) PD patients underwent a 123I-FP-CIT SPECT scan and a neuropsychological assessment. RESULTS: We showed a positive association between DAT availability in the head of the caudate nucleus and the Stroop Color Word Task - card I (reading words; ß = 0.32, P = 0.001) and a positive association between DAT availability in the anterior putamen and the Trail Making Test part A (connecting consecutively numbered circles; ß = 0.25, P = 0.02). These associations remained after adjusting for motor symptom severity or volume of the region-of-interest and were most pronounced in medication-naïve PD patients. There were no associations between cognitive performance and SERT availability in the thalamus or hippocampus. CONCLUSIONS: We interpret these results as a role for striatal dopamine - and its PD-related decline - in aspects of processing speed.

Hepatitis B vaccine-specific CD4(+) T cells can be detected and characterised at the single cell level: limited usefulness of dendritic cells as signal enhancers.

Hepatitis B surface antigen (HBsAg)-specific T cells were analysed in 16 healthy individuals vaccinated against hepatitis B, using optimised protocols. HBsAg-specific IFN-gamma producing CD4(+) T cells were found at a similar low frequency (0.01%) within the naive T cell subset, the central and the effector memory T cell subset. Overall, HBsAg-specific total CD4(+) T cells were detected in approximately 81% of the HBV vaccinees. The use of dendritic cells substantially increased the otherwise low proliferative responses but not the percentage of IFN-gamma producing cells. The analysis of readily detectable CMV-specific CD4(+) T cell responses was used as a positive control and confirmed the adequacy of our assays. T cell responses associated with (in-) adequate hepatitis B vaccination can now be analysed in more detail.

Functional impairment of monocyte-derived dendritic cells in patients with severe chronic kidney disease.

BACKGROUND: Dendritic cells (DCs) are antigen-presenting cells that are pivotal for the initiation of the primary immune response. Patients with chronic kidney disease (CKD) with or without chronic intermittent haemodialysis (CIHD) show an impaired immune response. Dysfunction of DCs may underlie this phenomenon. METHODS: In this study, several different functions of monocyte-derived DCs (moDC) of patients with CKD class IV-V (glomerular filtration rate <30 ml/min) and patients on CIHD were studied in vitro and compared with age- and sex-matched healthy volunteers. RESULTS: We demonstrate that, independent of the maturation stimulus used, mature moDC from both groups of patients did not acquire the same level of terminal differentiation as moDC from controls, as shown by analysis of cell surface markers and the relative high macropinocytosis activity of moDC. The stimulation of allogeneic T-cells by immature moDC and mature moDC did not differ between patients and controls. However, in the presence of immature moDC or antigen-loaded maturated moDC from patients, less proliferation of autologous T-cells was observed in response to recall antigens. There was no difference between moDC from controls and patients in their ability to activate naive T-cells and to differentiate them into Th1 and Th2 cells. CONCLUSIONS: These results show that the terminal differentiation of moDC in patients with severe CKD is impaired. This impairment is not restricted to one maturation stimulus and is independent of treatment with haemodialysis.

Progressive loss of renal function is associated with activation and depletion of naive T lymphocytes.

We hypothesized that progressive loss of renal function specifically affects certain T cell subsets. T lymphocyte subsets of patients with chronic kidney disease and healthy controls were characterized by flow cytometry using heparin-anticoagulated whole blood samples. Plasma interleukin (IL)-7 and IL-15 concentrations were determined as these cytokines are critically involved in T cell homeostasis. The results revealed that a progressive decrease in renal function is associated with activation and selective loss of naive T cells and CD4+ central memory cells and a marked increase in CD8+ memory T cells that lack CD45RO and CCR7. The profile of T cell subsets of patients with CKD 5 with or without hemodialysis treatment was similar except for a pronounced shift to Th1 cells in hemodialysis patients. IL-7 but not IL-15 plasma concentrations were lowered in patients with end-stage renal disease as compared to healthy controls.