Rheumatoid Arthritis: Methods and Protocols

244 Pages·2018·7.48 MB·English

by  Shuang Liu

Methods in
Molecular Biology 1868
Shuang Liu Editor
Rheumatoid
Arthritis
Methods and Protocols
M M B
ethods in olecular iology
Series Editor
John M. Walker
School of Life and Medical Sciences
University of Hertfordshire
Hatfield, Hertfordshire, AL10 9AB, UK
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Rheumatoid Arthritis
Methods and Protocols
Edited by
Shuang Liu
Department of Pharmacology, Ehime University Graduate School of Medicine,
Toon, Ehime, Japan
Editor
Shuang Liu
Department of Pharmacology
Ehime University Graduate School of Medicine
Toon, Ehime, Japan
ISSN 1064-3745 ISSN 1940-6029 (electronic)
Methods in Molecular Biology
ISBN 978-1-4939-8801-3 ISBN 978-1-4939-8802-0 (eBook)
https://doi.org/10.1007/978-1-4939-8802-0
Library of Congress Control Number: 2018954053
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Preface
Rheumatoid arthritis (RA) is the most common autoimmune inflammatory arthritis in
adults, affecting almost 1% of the world’s population. At present, fewer than 30% of patients
show robust responses to treatments. These treatments are associated with a number of
adverse side effects, including disease relapse and bone deformation of individual joints.
Thus, additional RA- and target-specific preclinical studies are required and further
optimization of the treatments is necessary prior to the clinical setting.
Rheumatoid Arthritis: Methods and Protocols summarizes the standard laboratory
protocols and methodology commonly used in basic and translational studies in the field of
RA treatment, including the establishment of basic RA models, evaluation of disease activity
and immunological status, and systemic drug delivery. Some timely topics and new research
tools are discussed—such as viral-mediated gene therapy and humanized xenograft RA
models—that enable the readers to broaden their research horizons. Established laboratory
techniques for the development of therapeutic regents such as antibiotics and nucleic acid
formulations are also discussed.
Rheumatoid Arthritis: Methods and Protocols represents a basic manual for clinical
researchers, including physicians, nurses, and pharmacists who are just getting started in the
field of intervention study. Protocols are described in a step-by-step manner, and notes
describing ways to optimize these methods are included so that investigators with little
experience can effectively utilize these protocols.
We would like to thank all of the contributors, who are leading researchers in the RA
field and expert users of the presented methods, for providing their protocols for this
volume. We greatly appreciate the invitation and continued support from Dr. John Walker,
Editor-in-Chief of the Methods in Molecular Biology series.
Toon, Ehime, Japan Shuang Liu
v
Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Part I anImal models
1 Collagen-Induced Arthritis Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Maya Miyoshi and Shuang Liu
2 Human Xenograft Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Shuang Liu
3 Long-Term Constant Subcutaneous Drug Administration . . . . . . . . . . . . . . . . . 17
Shuang Liu and Maya Miyoshi
4 Clinical Scoring of Disease Activity in Animal Models . . . . . . . . . . . . . . . . . . . . 23
Maya Miyoshi and Shuang Liu
5 Histological Analysis of Arthritic Joints . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Takeshi Kiyoi
6 Preparation of Joint Extracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Shuang Liu and Erika Takemasa
Part II theraPeutIc aPProach
7 Production of Immunizing Antigen Proteoliposome Using Cell-Free Protein
Synthesis System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Wei Zhou and Hiroyuki Takeda
8 Reconstruction of Protein/Liposome Complex . . . . . . . . . . . . . . . . . . . . . . . . . 69
Yasuyuki Suzuki
9 Production of Neutralizing Antibody . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Erika Takemasa, Shuang Liu, and Hitoshi Hasegawa
10 Autoantibody Profiling Using Human Autoantigen Protein
Array and AlphaScreen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Hiroyuki Takeda
11 Generation of Specific Aptamers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Shuang Liu, Yasuyuki Suzuki, and Makoto Inui
12 Production of Lentiviral Particles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Shuang Liu
13 RNA Interference Ex Vivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Shuang Liu
vii
viii Contents
14 Lentiviral-Mediated Systemic RNA Interference In Vivo . . . . . . . . . . . . . . . . . . 137
Shuang Liu
15 Mesenchymal Stem Cell Engineering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
Shuang Liu
Part III evaluatIon of ImmunologIcal status
16 Screening of Ca2+ Influx in Lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Erika Takemasa and Shuang Liu
17 Single-Cell Ca2+ Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
Shuang Liu
18 Electrophysiological Methods to Measure Ca2+ Current . . . . . . . . . . . . . . . . . . . 169
Shuang Liu and Miyuki Kuno
19 The Functional Assessment of T cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Saho Maruyama
20 Release of Antibodies and Cytokines from B Cells . . . . . . . . . . . . . . . . . . . . . . . 201
Shuang Liu
21 Evaluation of Autoreactive Responses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
Shuang Liu
22 Bone Resorption Activity in Mature Osteoclasts . . . . . . . . . . . . . . . . . . . . . . . . . 215
Takeshi Kiyoi
23 Animal Models of Vasculitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
M. Mogi and Shuang Liu
Part Iv clInIcal aPProach
24 Design an Intervention Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
Hitoshi Hasegawa
25 Assessment of Disease Activity, Structural Damage,
and Function in Rheumatoid Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
Hitoshi Hasegawa
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
Contributors
hItoshI hasegawa • Department of Hematology, Clinical Immunology and Infectious
Diseases, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
makoto InuI • Department of Pharmacology, Yamaguchi University Graduate School of
Medicine, Ube, Yamaguchi, Japan
takeshI kIyoI • Division of Analytical Bio-Medicine, Advanced Research Support Center,
Ehime University, Toon, Ehime, Japan
mIyukI kuno • Department of Molecular and Cellular Physiology, Osaka City University
Graduate School of Medicine, Osaka, Japan
shuang lIu • Department of Pharmacology, Ehime University Graduate School of
Medicine, Toon, Ehime, Japan
saho maruyama • Department of Immunology, Ehime University Graduate School of
Medicine, Toon, Ehime, Japan
maya mIyoshI • Department of Pharmacology, Ehime University Graduate School of
Medicine, Toon, Ehime, Japan
m. mogI • Department of Pharmacology, Ehime University Graduate School of Medicine,
Toon, Ehime, Japan
yasuyukI suzukI • Department of Pharmacology, Ehime University Graduate School of
Medicine, Toon, Ehime, Japan; Department of Anesthesiology, Saiseikai Matsuyama
Hospital, Matsuyama, Ehime, Japan
hIroyukI takeda • Proteo-Science Center, Ehime University, Matsuyama, Japan
erIka takemasa • Department of Pharmacology, Ehime University Graduate School of
Medicine, Toon, Ehime, Japan
weI zhou • Proteo-Science Center, Ehime University, Matsuyama, Japan
ix
Part I
Animal Models
Chapter 1
Collagen-Induced Arthritis Models
Maya Miyoshi and Shuang Liu
Abstract
Due to limitations of using patient-derived samples for systemic kinetic studies in rheumatoid arthritis
(RA) research, animal models are helpful for further understanding the pathophysiology of RA and seeking
potential therapeutic targets or strategies. The collagen-induced arthritis (CIA) model is one of the stan-
dard RA models used in preclinical research. The CIA model shares several pathological features with RA,
such as breach of tolerance and generation of autoantibodies targeting collagen, synovial inflammatory cell
infiltration, synovial hyperplasia, cartilage destruction, and bone erosion. In this chapter, a protocol for
successful induction of CIA in mice is described. In this protocol, CIA is induced by active immunization
by inoculation with type II heterologous collagen in Freund’s adjuvant in susceptible DBA/1 mice.
Key words Collagen-induced arthritis, Freund’s adjuvant, Type II collagen, Emulsion, Immunization
1 Introduction
Rheumatoid arthritis (RA) is a chronic inflammatory disease that
initially affects the joints, manifesting as pain, stiffness, and synovi-
tis, leading to cartilage and bone erosion by invading fibrovascular
tissue [1]. The central pathogenesis of RA is characterized by acti-
vation of macrophages by autoreactive T cells, resulting in the
release of a series of pro-inflammatory cytokines. However, how
the systemic chronic inflammatory state triggers the onset of artic-
ular disorder is still poorly understood [2]. To further define the
pathogenesis of RA, it is helpful to study human-derived cells and
explanted tissues from patients who have undergone arthroscopic
surgery or prosthetic replacement arthroplasty. However, this has
significant limitations for systemic kinetic studies. Therefore, ani-
mal models are not only essential to facilitate understanding of the
pathophysiology of RA and seek potential therapeutic targets or
strategies but also are the starting point for in vivo application of
new therapeutic agents.
Based on the methods of induction, systemically induced mod-
els include those elicited by active immunization, such as
Shuang Liu (ed.), Rheumatoid Arthritis: Methods and Protocols, Methods in Molecular Biology, vol. 1868,
https://doi.org/10.1007/978-1-4939-8802-0_1, © Springer Science+Business Media, LLC, part of Springer Nature 2018
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