Abstract Details

Title In-vivo B-cell activity predicts response to treatment with glatiramer acetate and interferons in patients with relapsing-remitting multiple sclerosis (RRMS)

Topic Multiple Sclerosis

Presentation(s) P9 - Poster Session 9 (12:00 PM-1:00 PM)

Poster/Presentation
Number 9-012

Objective Value of the enzyme-linked immunospot (ELISPOT) assay as a predictive marker for freedom of relapse activity in RRMS patients on glatiramer acetate (GA) versus interferon-ß (INF) using the ex-vivo detection of brain-reactive B cells

Background Pilot studies showed the potential of ELISPOT to predict clinical treatment response of RRMS patients to GA by in-vivo immunological response (1).

Design/Methods Peripheral blood mononuclear cells (PBMCs) of different RRMS groups were analysed: 68 resp. 55 treatment responders (>= 12m without relapses) to GA resp. INF as well as 35 GA resp. 37 INF treatment failures have been identified before using data of German NeuroTransData MS registry excluding previous or current treatment interfering with B-cell function.
After overnight resting of blood samples were isolated using Biocoll density gradient centrifugation. For polyclonal stimulation of B cells, PBMCs were cultured in RPMI-1640 supplemented with IL-2 and R848 for 96 h. 1 x 10⁶ cells were plated on whole normal human brain tissue lysate-coated wells and incubated for 26 h. Afterwards, spots were developed using the Vector Blue AP-kit and counted with an ImmunoSpot Series 6 Analyzer. Cut-off value for positive response was 4.5 B-cell spots

Results

50/68 GA responders, but only 7/35 GA failures demonstrated a positive ELISPOT response. Only 15/55 INF responders, but 27/37 INF failures were positive.

Validity measures for the prediction of freedom of relapse during treatment with GA and IF-ß, respectively, showed sensitivities of 0.74/0.73, specificities of 0.80/0.73, positive predictive value 0.88/0.64, negative predictive value 0.39/0.80.

Conclusions Testing of the brain-reactive B-cell response by ELISPOT can help with the treatment decision between GA vs. IFN treatment. ELISPOT positive patients are more likely to respond to GA and to be non-responsive to IFN and vice versa. Additional prospective studies have to be performed to establish the test in clinical practice.

Authors/Disclosures
Stefan Braune (Gemeinschaftspraxis) PRESENTER	Stefan Braune has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NeuroTransData. Stefan Braune has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Stefan Braune has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for NeuroTransData.
	No disclosure on file
Tjalf Ziemssen, MD, F�鶹��ýӳ�� (University Clinic Dresden)	Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS . Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roche. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Dresden Internation University. The institution of Dr. Ziemssen has received research support from Novartis. The institution of Dr. Ziemssen has received research support from Merck. The institution of Dr. Ziemssen has received research support from Sanofi. The institution of Dr. Ziemssen has received research support from BMS. The institution of Dr. Ziemssen has received research support from Roche.
	No disclosure on file
Arnfin Bergmann	Dr. Bergmann has nothing to disclose.
	No disclosure on file

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