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Intravenous Immunoglobulins in the Third
Millennium
Intravenous Immunoglobulins in
the Third Millennium
Edited by

Marinos C.Dalakas

National Institutes of Neurological Disorders and Stroke

National Institutes of Health
Bethesda, Maryland, USA

and

Peter J.Späth

ZLB Bioplasma AG
Bern, Switzerland

The Parthenon Publishing Group

International Publishers in Medicine, Science & Technology
A CRC PRESS COMPANY
BOCA RATON LONDON NEW YORK WASHINGTON,
D.C.
 Published in the USA by The Parthenon Publishing Group 345 Park Avenue South, 10th Floor
NewYork, NY 10010 USA
Published in the UK and Europe by The Parthenon Publishing Group 23–25 Blades Court Deodar
Road London SW15 2NU UK
Copyright © 2004 The Parthenon Publishing Group
Library of Congress Cataloging-in-Publication Data Data available on request
British Library Cataloguing in Publication Data Data available on request

ISBN 0-203-32594-X Master e-book ISBN

ISBN 1-84214-258-5 (Print Edition)

First published in 2004
This edition published in the Taylor & Francis e-Library, 2005.
“To purchase your own copy of this or any of Taylor & Francis or Routledge’s collection of
thousands of eBooks please go to http://www.ebookstore.tandf.co.uk/.
No part of this book may be reproduced in any form without permission from the publishers except
for the quotation of brief passages for the purposes of review

Composition by The Parthenon Publishing Group

 Content

List of speakers and chairpersons x

Foreword xxi

1
Two decades of experience with intravenous immunoglobulin

1. Manufacturing of intravenous immunoglobulin: challenges, achievements 3

and opportunities
A.Morell
2. Challenges and achievements in pathogen safety of intravenous 8
immunoglobulin
P.J.Späth and C.Kempf
3. Treatment modalities and clinical efficacy of immunoglobulin G 20
replacement therapies in primary immunodeficiency
A.D.B.Webster
4. Immunomodulation by intravenous immunoglobulin: idiopathic 28
thrombocytopenic purpura as a model
P.Imbach
5. Witnessing the introduction and use of intravenous immunoglobulin in 35
neurology
M.C.Dalakas
6. Pharmacoeconomics of intravenous immunoglobulin administration in 38
neurological disorders: the US experience
P.D.Donofrio
7. Pharmacoeconomics of intravenous immunoglobulin for polyneuropathies 43
P.McCrone

48
Intravenous immunoglobulin in immunodeficiencies and severe infections—
molecular aspects and clinical use

8. B-cell maturation to produce high-affinity antibodies of different isotypes 50

and its abnormalities
 A.Durandy
9. The molecular basis of primary immune deficiency diseases 55
H.D.Ochs, T.R.Torgerson, W.-I.Lee, Y.Z.Jin, E.Gambineri and Q.Zhu
10. Safety in intravenous immunoglobulin therapy 68
E.W.Gelfand
11. Immunoglobulin replacement by the subcutaneous route using preparations 74
licensed in the USA for administration by other routes
M.Berger, K.Duff, J.Poll and S.Roy
12. The use of intravenous immunoglobulin for allogeneic stem cell 78
transplantation: the US experience
R.H.Buckley
13. Intravenous immunoglobulin for bone marrow/stem cell transplantation: the 82
European experience
K.Theunissen, J.A.Maertens and M.A.Boogaerts
14. Secondary antibody deficiency following treatment of vasculitis: the use of 88
intravenous immunoglobulin
V.J Tormey and A.Burns
15. Intravenous immunoglobulin in the prevention and treatment of severe 91
infections
K.Werdan

99
Immunomodulatory and anti-inflammatory potential of intravenous
immunoglobulin

16. Mechanisms of action of intravenous immunoglobulin in autoimmune and 101

inflammatory diseases
M.D.Kazatchkine, J.Bayry, S.Lacroix-Desmazes and S.V.Kaveri
17. Role of intravenous immunoglobulin in reversing glucocorticoid 107
insensitivity or resistance
E.W.Gelfand
18. Modulating the balance of activating and inhibiting Fcγ receptors: 114
mechanism of intravenous immunoglobulin action
L.Pricop
19. Anti-inflammatory effects of intravenous immunoglobulin: Fcγ receptor 119
inhibition/blockade and non-Fcγ receptor-mediated mechanisms
J.W.Semple and A.H.Lazarus
20. Immune modulation by intravenous immunoglobulin: some remarks on the 124
role of Fc receptors
E.van Mirre and C.E.Hack
21. Intravenous immunoglobulin in reactive hemophagocytic syndrome: a 128
paradigm of Fcγ receptor and cytokine modulation
L.Mouthon
 22. Anti-inflammatory effects of intravenous immunoglobulin through 134
modulation of complement activities
H.U.Lutz and P.J.Späth
23. Changes in gene expression profile in the muscles of patients with 140
dermatomyositis and inclusion body myositis after therapy with intravenous
immunoglobulin: a microarray analysis correlating gene expression with
clinical outcome
R.Raju and M.C.Dalakas
24. In vitro studies of mechanisms of action of intravenous immunoglobulin in 145
Guillain—Barré syndrome and Miller—Fisher syndrome: a review
R.Gold, A.Weishaupt, M.Stangel, A.Chan and K.V.Toyka

152
Intravenous immunoglobulin for autoimmune diseases of the peripheral
nervous system

25. The immunological rationale for intravenous immunoglobulin in Guillain- 154

Barré syndrome and chronic inflammatory demyelinating
polyradiculoneuropathy
J.D.Pollard
26. Intravenous immunoglobulin for Guillain-Barré syndrome and chronic 163
inflammatory demyelinating polyradiculoneuropathy in adult patients
P.A.van Doorn
27. Clinical experience with intravenous immunoglobulin for treatment of 173
pediatric Guillain-Barré syndrome and chronic inflammatory demyelinating
polyradiculoneuropathy
A.J.Kornberg
28. Intravenous immunoglobulin for multifocal motor neuropathy 178
L.H.van den Berg
29. Intravenous immunoglobulins in paraproteinemic demyelinating 181
neuropathies
J.-M.Léger
30. Immunoglobulins in IgM antimyelin-associated glycoprotein and other 187
paraproteinemic neuropathies
G.Comi
31. Intravenous immunoglobulin for myasthenia gravis 192
P.Gajdos
32. Intravenous immunoglobulin in polymyositis and dermatomyositis 195
P.Chérin
33. Controlled studies with high-dose intravenous immunoglobulin in the 200
treatment of inclusion body myositis
M.C.Dalakas
 206
Intravenous immunoglobulin for autoimmune diseases of the central nervous
system

34. Immune mechanisms and treatment perspectives in multiple sclerosis 208

R.Hohlfeld
35. A review of controlled clinical trials of intravenous immunoglobulin in 215
multiple sclerosis
P.S.Sorensen
36. Intravenous immunoglobulin treatment for patients with primary or 221
secondary progressive multiple sclerosis
D.Pöhlau and U.Kallweit
37. What is the effective dose of intravenous immunoglobulin for treatment of 228
relapsing—remitting multiple sclerosis?
M.Lewanska, M.Siger-Zajdel and K.Selmaj
38. High-dose intravenous immunoglobulin in the treatment of patients with 241
stiff person syndrome: a controlled study
M.C.Dala
39. Intravenous immunoglobulin in acute disseminated encephalomyelitis 252
E.Marchioni, S.Ravaglia, A.Todeschini, A.Pichiecchio, C.Uggetti, G.Piccolo
and M.Ceroni

261
The use of intravenous immunoglobulin in dermatology

40. Intravenous immunoglobulin in dermatology 263

S.Jolles
41. The use of intravenous immunoglobulin therapy in the treatment of 267
autoimmune mucocutaneous blistering diseases
A.R.Ahmed
42. Treatment of atopic dermatitis, urticaria and psoriasis with intravenous 275
immunoglobulin
M.Rustin
43. Intravenous immunoglobulin in toxic epidermal necrolysis and Stevens— 281
Johnson syndrome
L.E.French
44. Intravenous immunoglobulin in the treatment of vasculitis 285
D.Jayne
 296
Emerging applications for intravenous immunoglobulin

45. Immunomodulation by intravenous immunoglobulin of alloantibodies to 298

human leukocyte antigen: clinical aspects in solid organ transplantation
D.Glotz, C.Antoine, P.Julia, B.Pegaz-Fiornet, A.Duboust, S.Boudjeltia,
R.Fraoui, M.Combes and J.Bariety
46. Role of intravenous immunoglobulin in the management of heart failure 305
H.Krum
47. Intravenous immunoglobulin: potential role in the management of severe 315
acute respiratory syndrome
H.H.Chng, K.P.Leong, B.Leung, B.Ang, Y.S.Leo, S.Loo, S.K.Goh, T.W.K.
Lew, L.Y Hsu,
E.Arul and D.Tai
48. Enhancement of the immune response to Mycobacterium tuberculosis by 321
high-dose intravenous immunoglobulin in mice
S.Jolles, E.Roy, V.Stavropoulos, S.Coade, E.Grigorieva, R.Tascon and
D.Lowrie

325
Potential applications for intravenous immunoglobulin

49. Intravenous immunoglobulin for treatment of recurrent miscarriage 327

L.A.E.Noens
50. Epilepsy and the immune system: is there a link? .332
L.G.Lagae
51. Intravenous immunoglobulin as an immunomodulatory agent in systemic 340
lupus erythematosus and lupus nephritis
Y.Sherer and Y.Shoenfeld
52. Intravenous immunoglobulin for fibrosis, atherosclerosis and malignant 344
conditions
I.Krause and Y.Shoenfeld

350
Summaries of poster sessions

53. Intravenous immunoglobulin for immune deficiencies and passive 352

immunization
I.Quinti, M.Cagliuso and F.Atuti
54. The use of intravenous immunoglobulin in hematology and transplantation 356
D Provan
 D.Provan
55. The use of intravenous immunoglobulin in neurology 361
W.K.Engel
56. The use of intravenous immunoglobulin for dermatological disorders 367
M.Sticherling
57. The use of intravenous immunoglobulin in collagen vascular and heart 372
diseases
A.H.Lazarus
58. Intravenous immunoglobulin: mechanisms of action 375
P.E.Williams
59. Pathogen safety and tolerability of intravenous immunoglobulin 379
F.Rossi
60. Pharmacoeconomics and evidence-based medicine 386
G.Antonini and A.Di Pasquale

Index 391
 List of speakers and chairpersons

A.R.Ahmed
Center for Blistering Diseases
New England Baptist Hospital
70 Parker Hill Avenue, Suite 208
Boston, MA 02120
USA
G.Antonini
Neurologic Clinic
2nd Faculty of Medicine
University of Rome ‘La Sapienza’
S.Andrea Hospital
Via di Grottarossa 1035
00189 Rome
Italy
V.Askanas
USC Neuromuscular Center
Good Samaritan Hospital
637 S.Lucas Ave
Los Angeles 90017
USA
M.Berger
Immunology Division
Department of Pedatrics
Rainbow Babies and Children’s Hospital
11100 Euclid Avenue
Cleveland, OH 44106
USA
R.H.Buckley
Box 2898 or 363 Jones Building
Duke University Medical Center
Durham, NC 27710
USA
P.Chérin
Médecine Interne
CHU Pitié-Salpétrière
47 Boulevard de l’Hôpital
75013 Paris
France
H.H.Chng
Department of Rheumatology, Allergy and Immunology
Tan Tock Seng Hospital
11 Jalan Tan Tock Seng
Singapore 308433
G.Comi
Department of Neurology
Ospedale San Raffaele
Via Olgettina 60
20132 Milano
Italy
M.C.Dalakas
Neuromuscular Diseases Section
NINDS, National Institutes of Health
Building 10, Room 4N248
10 Center Drive MSC, 1382
Bethesda, MD 20892
USA
J.Davies
ZLB Bioplasma AG
Wankdorfstrasse 10
3000 Bern
Switzerland
P.D.Donofrio
Department of Neurology
Wake Forest University School of Medicine
Medical Center Boulevard
Winston-Salem, NC 27157
USA
A.Durandy
Inserm U429
Hôpital Necker-Enfants Malades
149 Rue de Sèvres
75015 Paris
France
W.K.Engel
USC Neuromuscular Center
Good Samaritan Hospital
637 S.Lucas Avenue, 3rd Floor
Los Angeles 90017
USA
A.Etzioni
Meyer Children’s Hospital
Rambam Medical Center
31096 Haifa
Israel
L.E.French
Department of Dermatology
Geneva University Medical School
24 Rue Micheli-du-Crest
1211 Geneva 14
Switzerland
P.Gajdos
Hôpital Raymond Poincare
104 Boulevard Raymond Poincare
92380 Garches
France
E.W.Gelfand
Division of Cell Biology
Department of Pediatrics
National Jewish Medical and Research Center
1400 Jackson Street
Denver, CO 80206
USA
D.Glotz
Department of Nephrology
Hopital Européen Georges Pompidou
20 Rue Leblanc
75015 Paris
France
R.Gold
Neurologische Universitätsklinik
Josef-Schneider-str. 11
D-97080 Würzburg
Germany
C.E.Hack
Department of Clinical Chemistry
VU Medical Center
Amsterdam
The Netherlands
R.Hohlfeld
Institute for Clinical Neuroimmunology
Klinikum Großhadern
Marcgioninistr. 15
D-81366 Munich
Germany
Th.Hunziker
Dermatologische Universitäts-klinik
Inselspital
3010 Bern
Switzerland
P.Imbach
Head of Pediatric Hematology/Oncology
University Children’s Hospital UKBB
Ronnergass 8—P.O. Box
4005 Basel
Switzerland
D.Jayne
Vasculitis and Lupus Clinic
Addenbrooke’s Hospital
Cambridge CB2 2QQ
UK
S.Jolles
National Institute for Medical Research
Division of Mycobacterial Research
Mill Hill
London NW7 1AA
UK
S.V.Kaveri
INSERM U430
Institut des Cordeliers
15 Rue de l’Ecole de Médecine
75006 Paris
France
M.D.Kazatchkine
INSERM U430
Institut Biomedical des Cordeliers and
University Pierre et Marie Curie
15 Rue de l’Ecole de Medicine
75270 Paris
France
A.J.Kornberg
Department of Neurology
Royal Children’s Hospital
Flemington Road
Parkville
Victoria 3052
Australia
C.L.Koski
University of Maryland
School of Medicine
UMMS, Neurology
N4W46, 22 S Greene St.
Baltimore, MD 21201
USA
H.Krum
NHMRC Center of Clinical Research Excellence in Therapeutics
Departments of Epidemiology & Preventative Medicine
Monash University Central and Eastern Clinical School
Alfred Hospital
Melbourne, Victoria 3004
Australia
L.G.Lagae
Department of Pediatric Neurology
University Hospitals KU Leuven
Herestraat 49
B30000 Leuven
Belgium
A.H.Lazarus
Canadian Blood Services
St Michael’s Hospital, 30 Bond St
Toronto, Ontario
Canada M5B 1W8
J.-M.Léger
Fédération de Neurologie Mazarin
Hôpital de la Salpêtrière
47 Boulevard de l’Hôpital
75651 Paris
France
H.U.Lutz
Institute of Biochemistry
Swiss Federal Institute of Technology
ETH Hoenggerberg
HPMD 14.1
8093 Zurich
Switzerland
B.Manger
Medizinische Klinik
Universität Erlangen
Krankenhausstrasse 12
91054 Erlangen
Germany
E.Marchioni
Department of Neuroradiology
Neurologic Institute IRCCS ‘C.Mondino’
University of Pavia
Italy
P.McCrone
Senior Lecturer in Health Economics
PO24 Health Services Research Department
Institute of Psychiatry
King’s College London
De Crespigny Park
London SE5 8AF
UK
M.Meurer
Department of Dermatology
Dresden University of Technology
Fetscherstrasse 74
01307 Dresden
Germany
S.Misbah
John Radcliffe Hospital
Oxford OX3 9DU
UK
A.Morell
ZLB Bioplasma AG
Wankdorfstrasse 10
3000 Bern
Switzerland
L.Mouthon
Internal Medicine Department
Hôpital Cochin
27 Rue du Faubourg Saint Jacques
75014 Paris
France
L.A.E.Noens
Department of Internal Medicine
Ghent University Hospital
Ghent
Belgium
S.Nonoyama
National Defense Medical College
3.2 Namiki, Tokovazawa
Saitama
Saitama 359–8513
Japan
U.Nydegger
Cardiovascular Surgery
Inselspital
3010 Bern
Switzerland
H.D.Ochs
Professor of Department of Pediatrics
University of Washington School of Medicine
1959 NE Pacific St. Box 356320
Seattle, WA 98195
USA
D.Pöhlau
Department of Neurology
Multiple Sclerosis Center
Kamillus-Klinik Asbach
Hospitalstr. 6
53567 Asbach
Germany
J.D.Pollard
Institute of Clinical Neuroscience
Blackburn Building
The University of Sydney
NSW 2006
Australia
L.Pricop
Department of Medicine and Immunology
Weill Medical College of Cornell University
Hospital for Special Surgery
535 East 70th Street
NewYork, NY 10021
USA
D.Provan
Department of Haematology
Royal London Hospital
Whitechapel
London E1 1BB
UK
I.Quinti
Department of Allergy and Clinical Immunology
University of Rome ‘La Sapienza’
00185 Rome
Italy
F.Rossi
ex-AFSSAPS
1 Bis Avenue Franco-Russe
75007 Paris
France
M.Rustin
Dermatology Department
The Royal Free Hospital
Pond Street
London NW3 2QG
UK
G.Schäffner
Paul Ehrlich Institute
Section Monoclonal and Polyclonal
Paul Ehrlich-Str. 51–59
63225 Langen
Germany
K.Selmaj
Department of Urology
Medical University of Lodz
22 Kopcinskiego Street
90–153 Lodz
Poland
J.W.Semple
Department of Laboratory Medicine and Pathobiology
St Michael’s Hospital
30 Bond Street
Toronto, Ontario
Canada M5B 1W8
Y.Sherer
Department of Medicine B
Sheba Medical Center
Tel-Hashomer 52621
Israel
Y.Shoenfeld
Department of Medicine B
Sheba Medical Center
Tel-Hashomer 52621
Israel
J.Siegel
The Ohio State University Medical Center
410 W. 10th Ave 368 Doan Rd
Columbus, Ohio 43210
USA
P.S.Sorensen
MS Research Unit
The Neuroscience Centre
Department of Neurology
Copenhagen University Hospital
Rigshospitalet
Copenhagen
Denmark
P.J.Späth
ZLB Bioplasma AG
Wankdorfstrasse 10
3000 Bern
Switzerland
M.Sticherling
Department of Dermatology
University of Leipzig
Stephanstr. 11
04103 Leipzig
Germany
E.R.Stiehm
UCLA School of Medicine
Department of Pediatrics and Immunology
10833 Le Conte Ave
Los Angeles, CA 90095
USA
K.Suzuki
National Institute of Infectious Diseases
Toyama, Shinjuku-ku
Tokyo 162–8640
Japan
M.Swenson
University of Louisville
Lodi South Floyd St., Suite 500
Louisville, KY 40892
USA
K.Theunissen
Department of Hematology
UZ Gasthuisberg
Herestraat 49
3000 Leuven
Belgium
V.J.Tormey
Department of Clinical Immunology
Royal Free Hospital
Pond Street
London NW3 2Q
UK
P.Turner
ZLB Bioplasma AG
Wankdorfstrasse 10
3000 Bern 22
Switzerland
L.H.van den Berg
Department of Neurology, G03.22
University Medical Centre
P.O. Box 8550
3508 GA Utrecht
The Netherlands
P.van den Bergh
University Medical Center
Utrecht
P.O. Box 85500
3508 GA Utrecht
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