Dopamine transporter immunoreactivity in peripheral blood mononuclear cells in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a chronic progressive neuromuscular disorder of unknown etiology, characterized by weakness, muscle wasting, fasciculations, and increased reflexes, with conserved intellect and higher functions. The neuropathology of ALS is mostly confined to damage of the motor neurons in the cerebral cortex, some motor nuclei of the brainstem, and anterior horns of the spinal cord. However, there is evidence for the involvement of other neuronal systems in the disease. In particular, damage of the dopamine neurons has been shown by neurochemical and imaging studies in the brain and spinal cord of ALS patients. Recent reports suggest that peripheral blood mononuclear cells (PBMC) may represent a useful in vivo model to study neurochemical alterations that occur in neurodegenerative disorders. Here we demonstrate the significant reduction of dopamine transporter immunoreactivity in PBMC of patients affected by ALS with respect to healthy subjects. These results extend our knowledge of damage of the dopamine system in ALS to peripheral cells. Thus, the original concept of ALS as an isolated degeneration of motor neurons seems to extend to a more widespread understanding of the disease with involvement of other neuronal systems in the central as well as peripheral nervous system

Dopamine transporter immunoreactivity in peripheral blood lymphocytes in multiple system atrophy

Previous studies showed the reduction of dopamine transporter immunoreactivity (DAT-IR) in peripheral blood lymphocytes (PBL) in Parkinson's disease. Here we report the reduction of DAT-IR in PBL in the extrapyramidal variant of multiple system atrophy. These results suggest the reduction of DAT-IR in PBL in a variety of neurodegenerative disorders, provided the presence of damage of the central dopaminergic systems. The reduction of DAT-IR in PBL in these disorders may represent a compensatory phenomenon aimed at reducing intracellular dopamine influx and, consequently, dopamine-mediated aggravation of oxidative stress in these cells. © 2008 Springer-Verlag

Inhibition of protein S by autoantibodies in patients with acquired protein S deficiency

This study was undertaken to analyze antibodies to protein S (PS) in patients with an acquired PS deficiency. Plasma from symptomatic patients with acquired (n = 14) or congenital (n = 10) PS deficiency and LD healthy donors was screened for PS antibodies by immunoblotting and for anti-phospholipid antibodies. PS antibodies (IgG) were detected in five of the patients with acquired PS deficiency. These antibodies belonged to the G1 and G4 immunoglobulin subclasses. IgG fractions from the same 5 patients were shown to inhibit PS activity. The inhibition of PS activity by the 5 IgG fractions was shown to be time- and dose-dependent and was abolished following incubation with purified PS, while no effect was found after absorption with cardiolipin micelles. In addition, anticardiolipin monoclonal or human purified antibodies, failed to exert significant PS inhibition. These findings demonstrate that anti-PS antibodies are able to inhibit PS activity and that this is independent of anti-phospholipid antibodies. Given the clinical features of the patients, these antibodies should be regarded as an expression of the broad autoimmune syndrome involving the phospholipid-binding plasma proteins

Central and peripheral dopamine transporter reduction in Parkinson's disease

OBJECTIVE: Previous reports showed the reduction of dopamine transporter immunoreactivity in peripheral blood lymphocytes in Parkinson's disease. In this work, we sought to investigate the possible correlation between central and peripheral dopamine transporter immunoreactivity values in a group of 11 drug-naive patients with Parkinson's disease. METHODS: Densitometric measurements of dopamine transporter immunoreactivity in peripheral blood lymphocytes was accomplished as described recently, using a monoclonal antidopamine transporter antibody. Dopamine transporter binding in the caudate and putamen nuclei was measured by means of (123)I-fluopane single-photon emission computed tomography in the same patients. RESULTS: The results failed to show any significant correlation between dopamine transporter immunoreactivity in peripheral blood lymphocytes and the caudate or putamen dopamine transporter binding. Moreover, dopamine transporter immunoreactivity in peripheral blood lymphocytes was reduced also in the single patient with normal striatal dopamine transporter binding. DISCUSSION: These results indicate the lack of correlation between central and peripheral dopamine transporter reduction in Parkinson's disease, using the methodologies applied herein. They therefore suggest that the two phenomena are unlikely to share a common pathogenetic mechanism