Abstract Details

Title Kappa Free Light Chains Intrathecal Synthesis Biomarkers are Efficient Tools for the Diagnosis of Multiple Sclerosis: a Large Multicenter Cohort Study

Topic Multiple Sclerosis

Presentation(s) S19 - MS Biomarkers and Symptom Management (1:24 PM-1:36 PM)

Poster/Presentation
Number 003

Background KFLC seem to be an efficient tool in diagnosing immunoglobulin intrathecal synthesis and MS. We lack extensive cohort studies, particularly to establish a consensus cut-off of KFLCi and KFLC IF in both conditions.

Objective Determination of kappa free light chains (KFLC) index (KFLCi) and intrathecal fraction (KFLC IF) cut-off values for multiple sclerosis (MS)-related immunoglobulin intrathecal synthesis diagnosis and rule-out non-MS inflammatory disorders.

Design/Methods We conducted a retrospective multicenter study involving 13 French MS centers. Patients were included if they had a CNS disorder, excluding infections and tumors, and eligible data for cerebrospinal fluid (CSF) and serum KFLC, albumin, and a known oligoclonal band (OCB) status. According to their diagnosis, patients were separated into four groups, and MS was diagnosed according to the 2017 criteria.

Results 1,621 patients were analyzed (675 MS, 90 clinically isolated syndrome (CIS), 297 other inflammatory CNS disorders (OIND), and 559 non-inflammatory controls). The optimal cut-off value for MS-related immunoglobulin intrathecal synthesis was 8.63 for KFLCi and 67.3% for KFLC IF: AUC= 0.890 [0.873;0.905] and 0.891 [0.874;0.906] respectively, and performed better than OCB: AUC= 0.861 [0.842;0.878]; p<0.001 with a highest sensitivity for the same specificity. The optimal cut-off values for ruling-out OIND were 23.37 for KFLCi and 86.0% for KFLC IF. In this condition, both KFLC biomarkers had lower sensitivity (p<0.0001) but better specificity (p<0.0001) than OCB. Both KFLCi and IF had similar performances in diagnosing MS-related immunoglobulin intrathecal synthesis or ruling-out OIND (p=0.13 and p=0.99, respectively). In MS patients, multivariate analysis found that woman gender (p<0.01), young age (p<0.05) and evidence of disease activity (p<0.01) were the only factors associated with higher KFLCi values.

Conclusions KFLC biomarkers are efficient tools to confirm MS-related immunoglobulin intrathecal synthesis and, being a quantitative variable, can also rule out OIND. Moreover, KFLC biomarkers values are reproducible between centers.

Authors/Disclosures
Christine Lebrun Frenay, MD, FAAN (CRCSEP Neurologie) PRESENTER	Dr. Lebrun Frenay has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Revue Neurologique.
	No disclosure on file
Xavier Ayrignac	Xavier Ayrignac has nothing to disclose.
Kevin Bigaut	Kevin Bigaut has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Kevin Bigaut has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Helene Zephir (Hospital Roger Salengro)	Helene Zephir has received personal compensation in the range of $0-$499 for serving as a Consultant for BIogen Idec. Helene Zephir has received personal compensation in the range of $0-$499 for serving as a Consultant for novartis. Helene Zephir has received personal compensation in the range of $0-$499 for serving as a Consultant for BMS. Helene Zephir has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion.
	No disclosure on file
	No disclosure on file
Jonathan Ciron, MD (CHU Toulouse)	Jonathan Ciron, MD has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Jonathan Ciron, MD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Jonathan Ciron, MD has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Jonathan Ciron, MD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS - Celgene. Jonathan Ciron, MD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion.
	No disclosure on file
Damien Biotti	Damien Biotti has nothing to disclose.
Jean-Phillippe Camdessanche	Jean-Phillippe Camdessanche has nothing to disclose.
	No disclosure on file
	No disclosure on file
Olivier Casez, MD (CHU De Grenoble)	Dr. Casez has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Thibault Moreau	Thibault Moreau has nothing to disclose.
	No disclosure on file
Thomasset Audrey	Miss Audrey has nothing to disclose.
	No disclosure on file
	No disclosure on file
Aude Maurousset	Aude Maurousset has received personal compensation in the range of $0-$499 for serving as a Consultant for novartis. Aude Maurousset has received personal compensation in the range of $0-$499 for serving as a Consultant for merck. Aude Maurousset has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for roche.
	No disclosure on file
Mikael Cohen (Hopital Pasteur)	Mikael Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Roche, Merck, Ad scientiam, Novartis, Alexion, BMS.
	No disclosure on file
Saskia Bresch, MD (Chu Pasteur)	Dr. Bresch has nothing to disclose.
David Laplaud	No disclosure on file
	No disclosure on file
Jean Pelletier, MD, PhD (Dpt of Neurology, CHU Timone)	Dr. Pelletier has nothing to disclose.
	No disclosure on file
Pierre Labauge, MD	Dr. Labauge has nothing to disclose.
	No disclosure on file
	No disclosure on file
Jerome De Seze	Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma. Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma. Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma. Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma. Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma. Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma. Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma. Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma.
	No disclosure on file
	No disclosure on file
Eric Thouvenot, MD, PhD (CHU De Nimes - Hopital Caremeau)	Dr. Thouvenot has received personal compensation in the range of $0-$499 for serving as a Consultant for Biogen. Dr. Thouvenot has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biologix FZCo.. Dr. Thouvenot has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Thouvenot has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Thouvenot has received personal compensation in the range of $500-$4,999 for serving as a Consultant for HEALTHME. Dr. Thouvenot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Thouvenot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Thouvenot has received research support from Biogen. The institution of Dr. Thouvenot has received research support from Novartis. The institution of Dr. Thouvenot has received research support from Roche.
	No disclosure on file