Contributions
Abstract: P545
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: An increasing number of disease-modifying therapies (DMTs) is available for treating multiple sclerosis (MS); however, some immunomodulatory agents are associated with potentially severe side effects. The cell-adhesion molecule CD62L, which facilitates leukocyte extravasation, has been proposed as predictive marker for treatment tolerability. Nevertheless, pre-analytical procedures might increase the variability of the assay and limit its clinical usability. If the immediate analysis of CD62L expression of peripheral blood mononuclear cells (PBMCs) can aid in treatment decision-making is yet unclear.
Objective: We aimed to investigate the effect of various DMTs in MS on CD62L expression of CD3+CD4+ PBMCs in freshly collected blood samples.
Methods: We collected peripheral blood samples of patients with clinically isolated syndrome (CIS) and definite MS (n = 48/186; 62.4 % female; age median 35.7, IQR 29.9-45.2 years; disease duration median 7.16 IQR 3.38-13.43 years; Expanded Disability Status Scale (EDSS) score median 1.5, IQR 0.0-2.5), and healthy controls (n = 51; 39.2 % female; age median 49.1, IQR 34.1-60.9 years). In 98 CIS/MS patients one or more samples were collected during follow-up (median 113, IQR 78-163 days). CD3, CD4 and CD62L were analysed by means of FACS flow cytometry within one hour after blood sampling.
Results: CD62L expression of CD3+CD4+ PBMCs was significantly decreased in patients receiving natalizumab (n = 26) and fingolimod (n = 20), and slightly increased in patients who were treated with dimethyl fumarate (n = 15) compared to patients who received interferon (n = 90), glatiramer acetate (n = 30) or no DMT (n = 53) and controls (p < 0.001). CD62L expression showed temporal stability in patients who did not change DMT usage, but increased after natlizumab withdrawal and decreased upon fingolimod introduction. CD62L expression did not correlate with demographic and clinical data (i.e., age, gender, age at disease onset, disease duration, therapy duration, EDSS at time of sampling and during follow-up, and annualised relapse rate).
Conclusion: CD62L expression of CD3+CD4+ PBMCs is altered in patients treated with different DMTs when measured in freshly isolated samples. The clinical implication of CD62L changes under various DMTs warrants further investigation.
Disclosure: This study represents a sub-study supported by the Austrian Federal Ministry of Science, Research and Economics (core-study named 'BIG-WIG MS' (Bildgebung, Immunpathogenese, Gesundungsfaktoren - Wien, Innsbruck, Graz - bei Multiple Sklerose'; 'Neuroimaging, immunopathogenesis and salutogenic factors in MS - a collaborative effort of the universities of Vienna, Innsbruck and Graz')) and the Austrian MS research society (Multiple Sklerose Forschungsgesellschaft).
MM Voortman received funding from the Austrian Federal Ministry of Science, Research and Economics and was trained within the frame of the PhD Program Molecular Medicine of the Medical University of Graz.
P Greiner: nothing to disclose.
D Moser: nothing to disclose.
MH Stradner: nothing to disclose.
W Graninger: nothing to disclose.
A Moser: nothing to disclose.
B Haditsch: nothing to disclose.
C Enzinger has received funding for travel and speaker honoraria from Biogen Idec, Bayer Schering Pharma, Merck Serono, Shire, Novartis Genzyme and Teva Pharmaceutical Industries Ltd./Sanofi-Aventis; research support from Merck Serono, Biogen Idec, and Teva Pharmaceutical Industries Ltd./Sanofi-Aventis; is serving on scientific advisory boards for Bayer Schering Pharma, Biogen Idec, Genzyme, Merck Serono, Novartis, and Teva Pharmaceutical Industries Ltd./Sanofi-Aventis; and has acted as academic editor for PLOSOne.
S Fuchs serves on scientific advisory boards and/or has received speaker honoraria from Biogen Idec, Novartis, Genzyme, Merck, Roche and Teva Pharmaceutical Industries.
F Fazekas serves on scientific advisory boards for Biogen Idec, Sanofi Genzyme, Merck, Novartis, and Teva ratiopharm; serves on the editorial boards of the European Stroke Journal, Multiple Sclerosis Journal, Neurology, the Polish Journal of Neurology and Neurosurgery, and the Swiss Archives of Neurology and Psychiatry; provides consulting services for Actelion, Medday, Parexel and Teva ratiopharm and has received speaker honoraria from Merck, Genzyme-Sanofi and Teva ratiopharm.
J Fessler: nothing to disclose.
M Khalil has received funding for travel and speaker honoraria from Bayer, Novartis, Merck, Biogen, Roche and Teva ratiopharm; serves on scientific advisory boards for Biogen and Roche and received a research grant from Teva ratiopharm.
Abstract: P545
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: An increasing number of disease-modifying therapies (DMTs) is available for treating multiple sclerosis (MS); however, some immunomodulatory agents are associated with potentially severe side effects. The cell-adhesion molecule CD62L, which facilitates leukocyte extravasation, has been proposed as predictive marker for treatment tolerability. Nevertheless, pre-analytical procedures might increase the variability of the assay and limit its clinical usability. If the immediate analysis of CD62L expression of peripheral blood mononuclear cells (PBMCs) can aid in treatment decision-making is yet unclear.
Objective: We aimed to investigate the effect of various DMTs in MS on CD62L expression of CD3+CD4+ PBMCs in freshly collected blood samples.
Methods: We collected peripheral blood samples of patients with clinically isolated syndrome (CIS) and definite MS (n = 48/186; 62.4 % female; age median 35.7, IQR 29.9-45.2 years; disease duration median 7.16 IQR 3.38-13.43 years; Expanded Disability Status Scale (EDSS) score median 1.5, IQR 0.0-2.5), and healthy controls (n = 51; 39.2 % female; age median 49.1, IQR 34.1-60.9 years). In 98 CIS/MS patients one or more samples were collected during follow-up (median 113, IQR 78-163 days). CD3, CD4 and CD62L were analysed by means of FACS flow cytometry within one hour after blood sampling.
Results: CD62L expression of CD3+CD4+ PBMCs was significantly decreased in patients receiving natalizumab (n = 26) and fingolimod (n = 20), and slightly increased in patients who were treated with dimethyl fumarate (n = 15) compared to patients who received interferon (n = 90), glatiramer acetate (n = 30) or no DMT (n = 53) and controls (p < 0.001). CD62L expression showed temporal stability in patients who did not change DMT usage, but increased after natlizumab withdrawal and decreased upon fingolimod introduction. CD62L expression did not correlate with demographic and clinical data (i.e., age, gender, age at disease onset, disease duration, therapy duration, EDSS at time of sampling and during follow-up, and annualised relapse rate).
Conclusion: CD62L expression of CD3+CD4+ PBMCs is altered in patients treated with different DMTs when measured in freshly isolated samples. The clinical implication of CD62L changes under various DMTs warrants further investigation.
Disclosure: This study represents a sub-study supported by the Austrian Federal Ministry of Science, Research and Economics (core-study named 'BIG-WIG MS' (Bildgebung, Immunpathogenese, Gesundungsfaktoren - Wien, Innsbruck, Graz - bei Multiple Sklerose'; 'Neuroimaging, immunopathogenesis and salutogenic factors in MS - a collaborative effort of the universities of Vienna, Innsbruck and Graz')) and the Austrian MS research society (Multiple Sklerose Forschungsgesellschaft).
MM Voortman received funding from the Austrian Federal Ministry of Science, Research and Economics and was trained within the frame of the PhD Program Molecular Medicine of the Medical University of Graz.
P Greiner: nothing to disclose.
D Moser: nothing to disclose.
MH Stradner: nothing to disclose.
W Graninger: nothing to disclose.
A Moser: nothing to disclose.
B Haditsch: nothing to disclose.
C Enzinger has received funding for travel and speaker honoraria from Biogen Idec, Bayer Schering Pharma, Merck Serono, Shire, Novartis Genzyme and Teva Pharmaceutical Industries Ltd./Sanofi-Aventis; research support from Merck Serono, Biogen Idec, and Teva Pharmaceutical Industries Ltd./Sanofi-Aventis; is serving on scientific advisory boards for Bayer Schering Pharma, Biogen Idec, Genzyme, Merck Serono, Novartis, and Teva Pharmaceutical Industries Ltd./Sanofi-Aventis; and has acted as academic editor for PLOSOne.
S Fuchs serves on scientific advisory boards and/or has received speaker honoraria from Biogen Idec, Novartis, Genzyme, Merck, Roche and Teva Pharmaceutical Industries.
F Fazekas serves on scientific advisory boards for Biogen Idec, Sanofi Genzyme, Merck, Novartis, and Teva ratiopharm; serves on the editorial boards of the European Stroke Journal, Multiple Sclerosis Journal, Neurology, the Polish Journal of Neurology and Neurosurgery, and the Swiss Archives of Neurology and Psychiatry; provides consulting services for Actelion, Medday, Parexel and Teva ratiopharm and has received speaker honoraria from Merck, Genzyme-Sanofi and Teva ratiopharm.
J Fessler: nothing to disclose.
M Khalil has received funding for travel and speaker honoraria from Bayer, Novartis, Merck, Biogen, Roche and Teva ratiopharm; serves on scientific advisory boards for Biogen and Roche and received a research grant from Teva ratiopharm.