Huntington's disease (HD) is a progressive neurodegenerative disease caused by an unstable CAG trinucleotide repeat expansion. The need for biomarkers of onset and progression in HD is imperative, since currently reliable outcome measures are lacking. We used two-dimensional electrophoresis and mass spectrometry to analyze the proteome profiles in cerebrospinal fluid (CSF) of 6 pairs of HD patients and controls. Prothrombin, apolipoprotein A-IV (Apo A-IV) and haptoglobin were elevated in CSF of the HD patients in comparison with the controls. We used western blot as a semi-quantified measurement for prothrombin and Apo A-IV, as well as enzyme linked immunosorbent assay (ELISA) for measurement of haptoglobin, in 9 HD patients and 9 controls. The albumin quotient (Qalb), a marker of blood-brain barrier (BBB) function, was not different between the HD patients and the controls. The ratios of CSF prothrombin/albumin (prothrombin/Alb) and Apo A-IV/albumin (Apo A-IV/Alb), and haptoglobin level were significantly elevated in HD. The ratio of CSF prothrombin/Alb significantly correlated with the disease severity assessed by Unified Huntington's Disease Rating Scale (UHDRS). The results implicate that increased CSF prothrombin, Apo A-IV, and haptoglobin may be involved in pathogenesis of HD and may serve as potential biomarkers for HD.
Guillain-Barré Syndrome (GBS) is a rare autoimmune inflammatory polyneuropathy with a high risk of respiratory failure and unclear pathogenesis. Currently, there are no valid biomarkers for diagnosis of GBS. We used 2-DE and MS to analyze the protein profiles of five pairs of cerebrospinal fluid (CSF) samples of the GBS patients and the patient controls. Three proteins (orosomucoid, haptoglobin and apolipoprotein A-IV) were up-regulated, and two proteins (prostaglandin D2 synthase and transthyretin) were down-regulated in the CSF of the GBS patients. The CSF haptoglobin level, quantified by enzyme-linked immunosorbent assay, was significantly higher in the GBS patients (12.44 ± 2.70 μg/mL) compared to the chronic inflammatory demyelinating polyradiculoneuropathy (2.82 ± 0.83 μg/mL), viral meningitis (3.57 ± 0.97 μg/mL) and control patients (1.44 ± 0.35 μg/mL, p<0.05). This study indicated that protein profile analysis using a combination of 2-DE and MS provides an effective strategy for elucidating the pathogenesis and identifying potential CSF biomarkers for GBS. The raised intrathecal synthesis of haptoglobin specifically only in GBS patients, but not in patients with other neurological diseases examined, provides evidence of central nervous system involvement in GBS, and may be used as a potential diagnostic marker for GBS.
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