Table Of ContentResults and Problems in Cell Differentiation
51
Series Editors
Dietmar Richter, Henri Tiedge
Roland Martin • Andreas Lutterotti (eds.)
Molecular Basis
of Multiple Sclerosis
The Immune System
Editors
Roland Martin Andreas Lutterotti
Universitätsklinikum Hamburg-Eppendorf Clinical Department of Neurology
Institut für Neuroimmunologie und Innsbruck Medical University
Klinische Multiple-Sklerose-Forschung Anichstrasse 35
Falkenried 94 A-6020 Innsbruck
20251 Hamburg Austria
Germany [email protected]
Series Editors
Dietmar Richter Henri Tiedge
Center for Molecular Neurobiology The Robert F. Furchgott Center for Neural
University Medical Center Hamburg- and Behavioral Science
Eppendorf (UKE) Department of Physiology and
University of Hamburg Pharmacology
Martinistrasse 52 Department of Neurology
20246 Hamburg SUNY Health Science Center at Brooklyn
Germany Brooklyn, New York 11203
[email protected] USA
[email protected]
ISBN 978-3-642-14152-2 e-ISBN 978-3-642-14153-9
DOI 10.1007/978-3-642-14153-9
Springer Heidelberg Dordrecht London New York
Results and Problems in Cell Differentiation ISSN 0080-1844
Library of Congress Control Number: 2010930623
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Preface
Despite major efforts by the scientific community over the years, our understanding
of the pathogenesis or the mechanisms of injury of multiple sclerosis is still limited.
Consequently, the current strategies for treatment and management of patients,
which are sometimes based on unproven hypotheses, are limited in their efficacy.
The mechanisms of tissue protection and repair are probably even less understood.
Further, the knowledge of disease pathogenesis is often derived from animal mod-
els, and it is often not clear whether animal data apply to the human condition; e.g.
therapy for multiple sclerosis has failed many times. One reason for these limita-
tions is the enormous complexity of the disease and every facet of its pathogenesis,
the mechanisms of tissue injury, the diagnostic procedures and finally the efficacy
of treatments and their side effects. For individual researchers and clinicians it is
more and more difficult to oversee all aspects of the disease and to regularly review
the advances in different fields of research.
In this volume of the Springer book series “Results and Problems in Cell
Differentiation” we have tried to pay tribute to this high complexity by choosing
several topics from basic and clinical immunology, genetics, diagnostics and ther-
apy, which are discussed by outstanding experts in the field. It was the aim of all
authors to review the latest advances in their speciality, but foremost to highlight
the big challenges for the future.
We are aware that this series cannot include all the relevant aspects, but we hope
to have reached our aim of bridging different fields such as neurobiology, immuno-
logy, genetics and therapy. We would like to thank all authors for their
contributions.
Hamburg Roland Martin
June 2010 Andreas Lutterotti
v
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Contents
The Genetics of Multiple Sclerosis ......................................................... 1
Jan Hillert
Potential Triggers of MS ......................................................................... 21
Jane E. Libbey and Robert S. Fujinami
Immunological Basis for the Development of Tissue
Inflammation and Organ-Specific Autoimmunity
in Animal Models of Multiple Sclerosis ................................................. 43
Thomas Korn, Meike Mitsdoerffer, and Vijay K. Kuchroo
T-Cells in Multiple Sclerosis ................................................................... 75
Christopher Severson and David A. Hafler
B Cells and Antibodies in MS ................................................................. 99
Markus Reindl, Bettina Kuenz, and Thomas Berger
Cooperation of B Cells and T Cells in the Pathogenesis
of Multiple Sclerosis................................................................................. 115
Martin S. Weber and Bernhard Hemmer
Role of NK Cells and Invariant NKT Cells
in Multiple Sclerosis................................................................................. 127
Kaori Sakuishi, Sachiko Miyake, and Takashi Yamamura
Antigen Processing and Presentation in Multiple Sclerosis ................ 149
Christina Stoeckle and Eva Tolosa
Immune-Mediated CNS Damage ........................................................... 173
Katrin Kierdorf, Yiner Wang, and Harald Neumann
Neuro-Immune Crosstalk in CNS Diseases ........................................... 197
Martin Kerschensteiner, Edgar Meinl, and Reinhard Hohlfeld
vii
viii Contents
Prospects for Antigen-Specific Tolerance Based
Therapies for the Treatment of Multiple Sclerosis ............................... 217
Danielle M. Turley and Stephen D. Miller
Immuno-Therapeutic Potential of Haematopoietic
and Mesenchymal Stem Cell Transplantation in MS ........................... 237
Paolo A. Muraro and Antonio Uccelli
Multiple Sclerosis Therapies:
Molecular Mechanisms and Future ....................................................... 259
Paulo Fontoura and Hideki Garren
Examination of the Role of MRI in Multiple Sclerosis:
A Problem Orientated Approach ........................................................... 287
Henry F. McFarland
Index .......................................................................................................... 303
The Genetics of Multiple Sclerosis
Jan Hillert
Abstract After many years of slow progress in the genetic analysis of complex
diseases, including multiple sclerosis (MS), the past few years have eventually seen
the first steps of turning a frustrating quest into a success story with the identifica-
tion of a rapidly increasing number of confirmed disease promoting or protect-
ing genetic variants. The principal reason for the change in situation is numbers:
number of individuals assessed in the studies and number of genetic variations
available for genotyping. In short, we now know that it takes thousands of patients
to identify new genes but also to pinpoint the complex interplay of several genetic
factors within the strongest genetic locus in MS, the HLA gene complex. However,
the mission is not completed until the gene identification has been translated into
useful understanding of disease mechanisms, and this is likely to necessitate further
methodological progress as well as hard work in functional studies.
Obviously, the reason for gene identification is never going to be genetic coun-
seling or prenatal diagnosis as not even full knowledge of the genetic background
on MS will allow even 30% accuracy in disease prediction, i.e., the concordance
rate in female monozygotic twins. Therefore, it is only in the way that risk genes
reveal details of disease triggering events, or that severity genes influence mecha-
nisms driving the tissue damage, that genetic information is likely to be useful.
Abbreviations
CNS Central nervous system
EAE Experimental autoimmune encephalomyelitis
GWAS Genome wide association study
HLA Human leukocyte antigen
LD Linkage disequilibrium
J. Hillert
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
e-mail: [email protected]
Results Probl Cell Differ, DOI 10.1007/400_2009_13 1
© Springer-Verlag Berlin Heidelberg 2009
