https://orcid.org/0000-0002-3010-5677
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ABSTRACT
Objectives: Natalizumab (NTZ), a treatment indicated for patients with highly active Relapsing – Remitting Multiple Sclerosis (RRMS), is known to induce increased relative frequency of lymphocytes. Progressive Multifocal Leukoencephalitis (PML) is a rare but serious adverse event related to NTZ. Moreover, reduced L-selectin (CD62L) expression in T-cells in cryopreserved samples of patients with RRMS under NTZ has been proposed as a biomarker of pre-PML state. We explore the association between L-selectin expression in T-cells and hematological parameters in freshly processed samples of patients with RRMS under NTZ.
Methods: We studied L-selectin expression in patients with: RRMS under NTZ (n=34), fingolimod (FTY, n=14), interferon-beta (IFNβ, n=22), glatiramer acetate (GA, N=17); in 9 patients with secondary progressive (SP) MS and in 6 healthy controls. Twenty-two patients under NTZ and 6 patients under FTY were followed for 18 months. One NTZ-treated patient developed PML during the study.
Results: Patients under NTZ exhibited increased relative frequency of lymphocytes (40.02±1.45) compared to patients under first–line treatment (30.57±1.68, p<0.001) and to patients with SPMS (29±1.56, p=0.02), and a lower mean L-selectin expression in (69.39±1.73) compared to patients under first–line treatment (79.1±1.17, p=0.003). A negative correlation between the relative frequency of CD4+CD62L+ T-cells and the absolute lymphocyte counts (Pearson’s r=0.367, p=0.033) was observed.
Discussion: We hereby provide mechanistic insight in a possible pathway implicated in NTZ-related PML risk. These results further underline the need for thorough validation of L-selectin expression in T-cells as a potential pre-PML biomarker.
GRAPHICAL ABSTRACT
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Notes on contributors
Marina Kleopatra Boziki
Marina Kleopatra Boziki, MD, PhD, MSc, is an Assistant Professor of Neurology in the 2nd Neurological Department of the Aristotle University of Thessaloniki, with experience in clinical and experimental Neuroimmunology. Her special field of interest is the influence of gut commensal microbiota in Multiple Sclerosis (MS) and its mouse model of Experimental Autoimmune Encephalomyelitis (EAE). She has a PhD on experimental neuroimmunology studying the “immunomodulative properties of H. pylori in a mouse model of MS”. She participated as sub- or co-investigator in 14 multicenter clinical trials for MS and neurodegenerative diseases and in 3 funded Research Studies. Her research has been published in 48 publications in scientific Journals (PubMed), with 1696 citations (Scopus) and H-index = 18 (Scopus). She is a co-author of one “highly cited publication in the field” (Neuroimmunology) cited as “Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Berer K, Mues M, Koutrolos M, Rasbi ZA, Boziki M, Johner C, Wekerle H and Krishnamoorthy G. Nature, 479, 538-541,2011, DOI: 10.1038/nature10554” (568 citations; Source: ISI Web of Science). Data retrieved on 16/12/2019.
Theodoros Karapanayotides
Theodoros Karapanayotides, MD, PhD, is an Associate Professor of Neurology in the 2nd Neurological Department of the Aristotle University of Thessaloniki, specialized in the management of acute cerebral stoke. He was trained in the Centre Hospitalier Universitaire Vaudois-CHUV, Head: Professor Julien Bogousslavsky). As a specialized Neurologist he was trained in the management of acute cerebral stroke and in NeuroEcho in the stroke unitof the CHUV, funded by CHUV and the Empeirikion Foundation as a doctoral fellow. His research has been published in 51 publications in scientific Journals (PubMed).
Georgios Papadopoulos
Georgios Papadopoulos, MD, is a Neurologist currently working at the Neurological Department of the 401 General Military Hospital of Athens.
Roza Lagoudaki
Roza Lagoudaki, PhD, MSc, is a Biologist-Researcher, Faculty of the Laboratory of Physiology, Medical School, Aristotle University of Thessaloniki. She has an MSc in Molecular Neuroscience and she specializes in Experimental Neurology, Molecular Neurobiology, Neuroimmunology, Cell cultures and Neurobiochemistry.
Pamela Melo
Pamela Melo is a Biologist. She graduated from the Department of Biology, Aristotle University of Thessaloniki with a Diploma Thesis on Clinical Neuroimmunology.
Christos Bakirtzis
Christos Bakirtzis MD, MSc, PhD is a Neurologist, currently working as an Academic Scholar in the 2nd Neurological Department of the Aristotle University of Thessaloniki. He graduated from Medical School of Democritus University of Thrace, Greece. He has an MSc in Social Psychiatry (Democritus University of Thrace, Greece) and he conducted his PhD Thesis entitled “A study of reaction time and attention in prolonged cognitive tasks in multiple sclerosis” in Aristotle University of Thessaloniki.
Ioannis Nikolaidis
Ioannis Nikolaidis, MD, PhD is a Neurologist, currently working as an Academic Scholar in the 2nd Neurological Department of the Aristotle University of Thessaloniki. He graduated from Medical School of Aristotle University of Thessaloniki. He conducted his PhD Thesis entitled “Epidemiological – clinical – pathophysiological study of peripheral neuropathy at patients infected with human immuno deficiency virus” in Aristotle University of Thessaloniki.
Evdoxia Gounari
Evdoxia Gounari, MD, PhD is a Microbiologist working in the Laboratory of Immunology of the AHEPA University General Hospital of Thessaloniki. She has an expertise in T Cell Biology, Flow Cytometry, Immunology, Hematologic Neoplasms, Immunofluorescence Techniques and immunofixation. Her research has been published in 20 publications in scientific Journals (PubMed).
Vasiliki Tsavdaridou
Vasiliki Tsavdaridou, MD, PhD is a Microbiologist, Head of the the Laboratory of Immunology of the AHEPA University General Hospital of Thessaloniki. Her research has been published in 9 publications in scientific Journals (PubMed).
Lemonia Skoura
Lemonia Skoura, MD, PhD is an Associate Professor of Microbiology in the Aristotle University of Thessaloniki and the Director of the Laboratory of Microbiology of the AHEPA University General Hospital of Thessaloniki. She received field specialization by the PHLS Respiratory and Systemic Infection Laboratory, Central Public Health Laboratory, London, the Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, the Reference Laboratory of the Center for Infectious Disease of the Health Protection Agency, Colindale, London and the Department of Immunology – Histocompatibility of the General Hospital “Evanggelismos” in Athens. Her research has been published in 53 publications in scientific Journals (PubMed).
Theodora Afrantou
Theodora Afrantou, MD, PhD is a Neurologist working in the 2nd Neurological Department of the Aristotle University of Thessaloniki. She has an expertise in epilepsy and she is the Consultant Neurologist for the Laboratory of Electro-Encephalography (EEG) of the 2nd Neurological Department of the Aristotle University of Thessaloniki. She conducted her PhD Thesis entitled “Study of diagnostic, hormonological and neuro-psychological parameters by category selective patients” in the Aristotle University of Thessaloniki. Her research has been published in 8 publications in scientific Journals (PubMed).
Theano Tatsi
Theano Tatsi is the Nurse of the Multiple Sclerosis Unit of the 2nd Neurological Department of the Aristotle University of Thessaloniki. She has a BSc of the Nursing Department, Technological Educational Institute of Athens.
Eleni Grigoriadou
Eleni Grigoriadou is the Manager of Multiple Sclerosis Unit of the 2nd Neurological Department of the Aristotle University of Thessaloniki. She has a BSc in Physiotherapy form the Physiotherapy Department, Technological Educational Institute of Thessaloniki. She specializes in Neurological Μedical Ιncidents – Multiple Sclerosis.
Eleni Polyzoidou
Eleni Polyzoidou, MD, PhD, is a Pathologist currently working in the Multiple Sclerosis Unit of the 2nd Neurological Department of the Aristotle University of Thessaloniki. She has a PhD in Experimental Neuroscience and she specialized in Experimental Neurology, Neuropathology, Neuroimmunology and Cell cultures. Her research has been published in 12 publications in scientific Journals (PubMed).
Nikolaos Mandoras
Nikolaos Mandoras is an undergraduate student of Business Administration in University of Macedonia with specialization in Marketing and Operations Management. Due to his studies and work experience he has developed expertise in the fields of Marketing, Consumers’ Behavior and Project Management. He is currently working as Administrative in the Multiple Sclerosis Unit of the 2nd Neurological Department of the Aristotle University of Thessaloniki.
Virginia Giantzi
Virginia Giantzi, MD, PhD is a Neurologist working in the 2nd Neurological Department of the Aristotle University of Thessaloniki. She has an expertise in Neurophysiology and she is the Consultant Neurologist for the Laboratory of Evoked Potentials of the 2nd Neurological Department of the Aristotle University of Thessaloniki. She conducted her PhD Thesis entitled “The kinetics of interferon-β-neutralizing antibodies in patients with multiple sclerosis during relapses” in the Aristotle University of Thessaloniki. Her research has been published in 5 publications in scientific Journals (PubMed).
Anna Kalogera - Fountzila
Anna Kalogera - Fountzila, MD, PhD is an Associate Professor of Radiology in the Aristotle University of Thessaloniki and Head of the Department of Radiology of the AHEPA University General Hospital of Thessaloniki. Her research has been published in 65 publications in scientific Journals (PubMed).
Panagiotis Ioannidis
Panagiotis Ioannidis, MD, PhD is an Associate Professor of Neurology in the 2nd Neurological Department of the Aristotle University of Thessaloniki, specialized in the management of dementia and other neurodegenerative diseases. He was specialized in the National Hospital for Neurology and Neurosurgery, UCLHospitals by participating in the Dementia Research Group as a specialist clinical fellow. His research has been published in 59 publications in scientific Journals (PubMed).
Dimitrios Parissis
Dimitrios Parissis MD, PhD is an Assistant Professor of Neurology in the 2nd Neurological Department of the Aristotle University of Thessaloniki, specialized in the management of neuromuscular diseases. He is the Consultant Neurologist for the Laboratory of Electromyography of the 2nd Neurological Department of the Aristotle University of Thessaloniki. He was specialized in Clinical Neurophysiology in the University College London Hospitals. His research has been published in 19 publications in scientific Journals (PubMed).
Sygkliti-Henrietta Pelidou
Sygkliti-Henrietta Pelidou, MD, PhD is an Ass. Professor of Neurology in the University of Ioannina, currently working as a Visiting Professor in the Laboratory of Experimental Neurology and Neuroimmunology of the 2nd Neurological Department of the Aristotle University of Thessaloniki. Her research has been published in 47 publications in scientific Journals (PubMed).
Sofia Zoidou
Sofia Zoidou, MSc is a graduate of the Faculty of Education of the Aristotle University of Thessaloniki. She has a Master’s in Neurosciences and Education form the Department of Education and Social Policy, University of Macedonia. Her thesis was on Experimental Neuroscience, entitled "Immunohistochemical Study of Inflammation, Demyelination and Axial Loss in Experimental Spinal Cord with Experimental Autoimmune Encephalomyelitis under Intense Physical Exercise".
Nikolaos Grigoriadis
Nikolaos Grigoriadis, MD, PhD is a Professor of Neurology, Aristotle University of Thessaloniki, Head of B’ Department of Neurology, AHEPA University Hospital, Head of the Multiple-Sclerosis Centre and Head of the Laboratory of Experimental Neurology and Neuroimmunology. He has been specialized in Experimental Neuroscience as a Visitor scientist in the Department of Neurology and Laboratory of Neuroimmunology, Hadassah Hebrew University, Jerusalem, Israel (Supervisors: Prof O. Abramsky, Prof D. Karussis) and in Neuropathology and Neuroimmunology, in the Brain Research Institute, Medical University of Vienna, Austria (Prof. H./ Lassmann). His research has been published in 179 publications in scientific Journals (PubMed).