Gene association with HLA suggests involvement of immune mediated mechanisms in the pathogenesis of Parkinson's disease (PD). Only a small number of studies have found differences between circulating leukocyte populations in PD patients compared to controls, with conflicting results. To clarify whether there is a circulating leukocyte PD phenotype, we assessed the numbers of T, B and natural killer cells, and monocytes and found a small reduction (15-25%) in CD4+ T and CD19+ B cells in PD. These findings suggest some compromise in immune cells in PD and have potential implications for immune function and the progression of PD.

Bernard–Soulier syndrome (BSS) is a rare autosomal recessive bleeding disorder characterized by defects of the GPIb‐IX‐V complex, a platelet receptor for von Willebrand factor (VWF). Most of the mutations identified in the genes encoding for the GP1BA (GPIbα), GP1BB (GPIbβ), and GP9 (GPIX) subunits prevent expression of the complex at the platelet membrane or more rarely its interaction with VWF. As a consequence, platelets are unable to adhere to the vascular subendothelium and agglutinate in response to ristocetin. In order to collect information on BSS patients, we established an International Consortium for the study of BSS, allowing us to enrol and genotype 132 families (56 previously unreported). With 79 additional families for which molecular data were gleaned from the literature, the 211 families characterized so far have mutations in the GP1BA (28%), GP1BB (28%), or GP9 (44%) genes. There is a wide spectrum of mutations with 112 different variants, including 22 novel alterations. Consistent with the rarity of the disease, 85% of the probands carry homozygous mutations with evidence of founder effects in some geographical areas. This overview provides the first global picture of the molecular basis of BSS and will lead to improve patient diagnosis and management.

Background GFI1B is a transcription factor important for erythropoiesis and megakaryocyte development but previously unknown to be associated with human disease. Methods A family with a novel bleeding disorder was identified and characterized. Genetic linkage analysis and massively parallel sequencing were used to localize the mutation causing the disease phenotype on chromosome 9. Functional studies were then performed in megakaryocytic cell lines to determine the biological effects of the mutant transcript. Results We have identified a family with an autosomal dominant bleeding disorder associated with macrothrombocytopenia, red cell anisopoikilocytosis, and platelet dysfunction. The severity of bleeding is variable with some affected individuals experiencing spontaneous bleeding while other family members exhibit only abnormal bleeding with surgery. A single nucleotide insertion was identified in GFI1B that predicts a frameshift mutation in the fifth zinc finger DNA‐binding domain. This mutation alters the transcriptional activity of the protein, resulting in a reduction in platelet α‐granule content and aberrant expression of key platelet proteins. Conclusions GFI1B mutation represents a novel human bleeding disorder, and the described phenotype identifies GFI1B as a critical regulator of platelet shape, number, and function.

Summary. Background: Depression is associated with an increased risk of cardiovascular disease (CVD). Although the mechanism is uncertain, prothrombotic and inflammatory factors may play a role. Objectives: As platelets play a key role in CVD, we determined first, whether depressed individuals had more activated platelets than non‐depressed individuals and second, whether treatment of depression reduced platelet activation levels. Patients/methods: We recruited 108 depressed outpatients and 45 control subjects all without a history of CVD. After psychological assessment, the depressed patients were offered treatment with medication and/or psychotherapy. Flow cytometric markers of platelet activation and level of depression were assessed at baseline and at 4 weeks and 6 months after treatment. Results: Depression was associated with increased platelet activation with a higher number of circulating CD62p (0.76 × 10⁹ L⁻¹ vs. 0.46, P = 0.019) and CD63 (P = 0.05) positive platelets compared with controls. Patients with depression also had more circulating platelet‐leukocyte aggregates than controls (P < 0.001). There was a positive correlation between the severity of depression and the level of platelet activation. Platelets from depressed patients were also hyperreactive to adenosine 5´‐diphosphate (ADP) stimulation with increased CD62p and CD63 exposure (P = 0.003 and 0.019, respectively). Six months of treatment resulted in a reduced number of circulating CD62p and CD63 positive platelets (29.84% and 53.38% decrease) and a 20.9% reduction in CD63 exposure after ADP activation. Conclusions: Depression is associated with increased in vivo platelet activation and resolution of depression using psychotherapy and/or medication reduces platelet activation. These findings provide insights into the link between depression and cardiovascular risk.