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- Kruse, N., et al.
(author)
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Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study
- 2015
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 36:9, s. 2587-2596
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Journal article (peer-reviewed)abstract
- Decreased levels of alpha-synuclein (aSyn) in cerebrospinal fluid (CSF) in Parkinson's disease and related synucleinopathies have been reported, however, not consistently in all cross-sectional studies. To test the performance of one recently released human-specific enzyme-linked immunosorbent assay (ELISA) for the quantification of aSyn in CSF, we carried out a round robin trial with 18 participating laboratories trained in CSF ELISA analyses within the BIOMARKAPD project in the EU Joint Program -Neurodegenerative Disease Research. CSF samples (homogeneous aliquots from pools) and ELISA kits (one lot) were provided centrally and data reported back to one laboratory for data analysis. Our study showed that although factors such as preanalytical sample handling and lot-to-lot variability were minimized by our study design, we identified high variation in absolute values of CSF aSyn even when the same samples and same lots of assays were applied. We further demonstrate that although absolute concentrations differ between laboratories the quantitative results are comparable. With further standardization this assay may become an attractive tool for comparing aSyn measurements in diverse settings. Recommendations for further validation experiments and improvement of the interlaboratory results obtained are given. (C) 2015 Elsevier Inc. All rights reserved.
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- Rot, U, et al.
(author)
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Impression of clinical worsening fails to predict interferon-beta neutralizing antibody status
- 2008
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In: The Journal of international medical research. - : SAGE Publications. - 0300-0605 .- 1473-2300. ; 36:6, s. 1418-1425
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Journal article (peer-reviewed)abstract
- The development of neutralizing antibodies (NAbs) against interferon-β (IFNβ) reduces clinical efficacy and markers of bioactivity in patients with multiple sclerosis (MS), although it has also been shown that a poor response to IFNβ coincided with unexpectedly low NAb levels. To try and resolve this incoherency, this study investigated 2822 patients referred to a NAb testing facility. The reason for NAb testing was indicated for 2506 patients: routine testing (76%), worsening of disease (14%) and other reasons (10%). Overall, 31% of patients were NAb positive and 17% had titres high enough to obliterate IFNβ bioactivity. The frequency of NAbs was similar in patients in the routine testing group compared with the worsening group. Samples showing high titres failed to be associated with worsening of symptoms. The study failed to show low NAb levels in patients responding poorly to IFNβ. It is concluded that it is not possible to predict NAb status by clinical impression of treatment response. This is likely to be an effect of the partial efficacy of IFNβ. Thus routine testing for NAbs must be carried out in order to identify NAb status in patients with MS.
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- Sominanda, A, et al.
(author)
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Interferon beta preparations for the treatment of multiple sclerosis patients differ in neutralizing antibody seroprevalence and immunogenicity
- 2007
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 13:2, s. 208-214
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Journal article (peer-reviewed)abstract
- Development of neutralizing antibodies (NAbs) reduces the clinical efficacy of interferon beta (IFNβ) treatment in multiple sclerosis (MS) patients. The aim of this study was to evaluate NAb seroprevalence (frequency of patients with NAbs) and immunogenicity (titer levels) of IFNβ preparations in a clinical setting. We analysed 1115 consecutive MS patients, treated with one of the three available IFNβ preparations, for an average of 40 months (1 – 120 months), for the presence of NAbs with the MxA protein induction assay. Overall, 32% of patients were positive for NAbs with neutralizing titers above 10. The frequency of NAbs, ie, the seroprevalence, was 13% in Avonex-treated patients, 43% for Betaferon, 39% for Rebif22 and 30% for Rebif44. In addition, the potential to induce high titer levels, ie, the immunogenicity, was observed to differ between preparations. Avonex, showing the lowest seroprevalence, also showed low immunogenicity and typically induced low titers. Betaferon, showing the highest seroprevalence when inducing NAbs, induced lower titers compared to Rebif22 and Rebif44. Treatment duration over five years only marginally correlated with decreased seroprevalence and titer levels. In conclusion, NAbs to IFNβ are common in a clinical setting and the IFNβ preparations differ not only in NAb seroprevalence, but also in immunogenicity. Multiple Sclerosis 2007; 13: 208–214. http://msj.sagepub.com
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