Azienda Ospedaliero Universitaria Maggiore della Carità of Novara

Author Of 1 Presentation

Biomarkers and Bioinformatics Oral Presentation

PS03.02 - Biomarkers of neurodegeneration, in particular Tau protein, may predict early disability in Multiple Sclerosis patients.

Speakers
Presentation Number
PS03.02
Presentation Topic
Biomarkers and Bioinformatics
Lecture Time
10:45 - 10:57

Abstract

Background

Neurodegeneration in Multiple Sclerosis (MS) occurs from early disease stages. Cerebrospinal fluid (CSF) Tau protein and beta-amyloid
protein (Abeta) are currently markers used in other neurodegenerative diseases. Several molecules, including Tau and Abeta, have been
investigated as suitable biomarkers of axonal damage in MS, but none is routinely used in clinical practice, also due to conflicting results.

Objectives

To evaluate if CSF Tau and Abeta protein, evaluated at the diagnosis, could predict early MS disability obtained at last clinical follow-up and to evaluate a possible correlation between CSF Tau and Abeta protein with radiological prognostic markers also collected at the diagnosis (baseline).

Methods

CSF Abeta and Tau levels were determined with commercial enzyme-linked immunosorbent assay in newly diagnosed MS patients. We collected demographic, clinical, and radiological data at baseline and at last clinical follow-up. We evaluated early disability using the MS severity score (MSSS) and the MSSS age-related score (ARMSS) at last follow-up as disability outcome, and global T2 white matter lesion load (LL) with a cut-off of 9 lesions and the presence or absence of spinal cord lesions as radiological baseline prognostic markers

Results

We enrolled 109 patients, 82 with a relapsing-remitting MS and with a mean follow-up of 4 years (SD±5y). Mean CSF values of Tau and Abeta were respectively 128,5±69 pg/ml and 557,7±258,6 pg/ml. Patients with higher CSF Tau levels at diagnosis developed higher disability evaluated with MSSS (R:0,3361, p=0,0003) and ARMSS (R:0,3088, p=0,001). At the moment, no correlations were found for Abeta and early disability markers. We also found a trend of higher Tau level and lower Abeta levels with higher T2 white matter LL and spinal cord involvement, still statistically not significant.

Conclusions

Our results showed a predictive role of neurodegenerative CSF markers, in particular Tau protein, in identifying early disability and worse prognosis in MS patients, indipendently from age. To our knowledge no other studies report a correlation of CSF Tau with both MSSS and ARMSS. Longer follow-up, larger population and extended analysis of radiological data are needed, to confirm a predictive and prognostic role of our biomarkers both at baseline and follow up.

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Author Of 1 Presentation

Biomarkers and Bioinformatics Poster Presentation

P0094 - Inter-laboratory evaluation of cerebrospinal fluid and serum kappa free light chain measurements (ID 966)

Abstract

Background

The kappa index, calculated by dividing the cerebrospinal (CSF)/serum kappa free light chain (KFLC) ratio by the CSF/serum albumin ratio, is gaining increasing interest as an indirect marker of intrathecal activation of the humoral immune response. The demonstration of intrathecal synthesis is of particular relevance in the diagnostic work-up of suspected Multiple Sclerosis. However, the lack of consistent data on inter-laboratory agreement in CSF and serum KFLC measurements is one of the factors that hamper the use of kappa index in routine practice.

Objectives

Aim of this study was to assess agreement in CSF and serum KFLC measurements and kappa index values across different laboratories.

Methods

Fifteen paired CSF and serum samples were analyzed in all participating laboratories (nr=8). Four centers used Binding Site instruments and assays, 3 centers used Siemens instruments and assays, and one center used a Siemens instrument and a Binding Site assay.

Absolute individual agreement between laboratories was calculated using a two-way mixed effects intraclass correlation coefficient (ICC). Cohen's kappa coefficient was used to measure inter-laboratory agreement on positive (5.8) kappa index values.

Results

Within Binding Site laboratories, ICC for KFLC measurements was 0.96 (95%CI: 0.9-0.98) for CSF, 0.93 (95%CI: 0.63-0.98) for serum and 0.97 (95%CI: 0.94-0.99) for kappa index values. Within Siemens laboratories, ICC for KFLC measurements was 0.99 (95%CI: 0.97-100) for CSF, 0.93 (95%CI: 0.48-0.98) for serum and 0.95 (95%CI: 0.89-0.98) for kappa index values. ICC calculated for all laboratories was 0.93 (95%CI: 0.87-0.97) for CSF KFLC, 0.81 (95%CI: 0.53-0.93) for serum KFLC and 0.65 (95%CI: 0.43-0.84) for kappa index. Cohen's kappa coefficient for a positive kappa index was 0.89 across Binding Site laboratories, 0.70 across Siemens laboratories, and 0.77 across all laboratories.

Conclusions

There was an excellent agreement in CSF KFLC measurements and in kappa index values within laboratories using the same instrument and assay (Binding Site or Siemens), while serum KFLC measurements were less concordant. Agreement across all laboratories was decreased when including the laboratory using a Siemens instrument coupled with a Binding Site assay in the analyses. Concordance for a positive kappa index was substantial across all laboratories and within Siemens laboratories, and very good within Binding Site laboratories.

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