scholarly journals Mouse Models of Rheumatoid Arthritis for Studies on Immunopathogenesis and Preclinical Testing of Fc Receptor-Targeting Biologics

Pharmacology ◽  
2020 ◽  
Vol 105 (11-12) ◽  
pp. 618-629
Author(s):  
Bonnie J.B. Lewis ◽  
Donald R. Branch
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Autoimmune Diseases ◽  
Mouse Models ◽  
Preclinical Testing ◽  
Systemic Complications ◽  
Chronic Autoimmune Disease

<b><i>Background:</i></b> Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation, swelling, and pain in the joints and involves systemic complications. Mouse models of RA have been extensively used to model the pathogenesis of RA and to develop effective therapies. Although many components of the immune system have been studied in these models, the role of crystallizable fragment (Fc) gamma receptors (FcγRs) in RA has been sorely neglected. The aim of this review was to introduce the different mouse models of RA and to describe the different drug development strategies that have been tested in these models to target FcγR function, with the focus being on drugs that have been made from the Fc of immunoglobulin G (IgG). <b><i>Summary:</i></b> Evidence suggests that FcγRs play a major role in immune complex-induced inflammation in autoimmune diseases, such as RA. However, there is limited knowledge on the importance of FcγRs in the human disease even though there has been extensive work in mouse models of RA. Numerous mouse models of RA are available, with each model depicting certain aspects of the disease. Induced models of RA have nonspecific immune activation with cartilage-directed autoimmunity, whereas spontaneous models of RA develop without immunization, which results in a more chronic form of arthritis. These models have been used to test FcγR-targeting monoclonal antibodies, intravenous immunoglobulin (IVIg), subcutaneously administered IVIg, and recombinant Fcs for their ability to interact with and modify FcγR function. Recombinant Fcs avidly bind FcγRs and exhibit enhanced therapeutic efficacy in mouse models of RA. <b><i>Key Message:</i></b> The therapeutic utility of targeting FcγRs with recombinant Fcs is great and should be explored in human clinical trials for autoimmune diseases, such as RA.

scholarly journals B-Cell Pathology in Juvenile Idiopathic Arthritis

Arthritis ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
V. Wiegering ◽  
H. J. Girschick ◽  
H. Morbach
Keyword(s):  
Rheumatoid Arthritis ◽  
Juvenile Idiopathic Arthritis ◽  
Targeted Therapy ◽  
B Cells ◽  
Autoimmune Diseases ◽  
B Cell ◽  
Mouse Models ◽  
Chronic Arthritis ◽  
Common Cause

Juvenile Idiopathic Arthritis (JIA) is the most common cause of chronic arthritis in childhood and adolescents and encompasses a heterogeneous group of different diseases. Due to the promising results of B-cell depleting therapies in rheumatoid arthritis the role of B-cells in autoimmune diseases has to be discussed in a new context. Additionally, experiments in mouse models have shed new light on the antibody-independent role of B-cells in the development of autoimmune diseases. In this review we will discuss the importance of B-cells in the pathogenesis of JIA appraising the question for an immunological basis of B-cell targeted therapy in JIA.

scholarly journals Mast Cell and Autoimmune Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Yunzhi Xu ◽  
Guangjie Chen
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Mast Cell ◽  
Immune System ◽  
Mast Cells ◽  
Autoimmune Diseases ◽  
Innate Immune System ◽  
Innate Immune ◽  
Current Stage

Mast cells are important in innate immune system. They have been appreciated as potent contributors to allergic reaction. However, increasing evidence implicates the important role of mast cells in autoimmune disease like rheumatoid arthritis and multiple sclerosis. Here we review the current stage of knowledge about mast cells in autoimmune diseases.

scholarly journals The Role of Monoclonal Antibodies in Smoldering and Newly Diagnosed Transplant-Eligible Multiple Myeloma

2020 ◽  
Vol 13 (12) ◽  
pp. 451
Author(s):  
Elena Zamagni ◽  
Paola Tacchetti ◽  
Paola Deias ◽  
Francesca Patriarca
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Survival Outcomes ◽  
Newly Diagnosed ◽  
Cellular Targets ◽  
Recent Introduction

The recent introduction of monoclonal antibodies (MoAbs), with several cellular targets, such as CD-38 (daratumumab and isatuximab) and SLAM F7 (elotuzumab), differently combined with other classes of agents, has significantly extended the outcomes of patients with multiple myeloma (MM) in different phases of the disease. Initially used in advanced/refractory patients, different MoAbs combination have been introduced in the treatment of newly diagnosed transplant eligible patients (NDTEMM), showing a significant improvement in the depth of the response and in survival outcomes, without a significant price in terms of toxicity. In smoldering MM, MoAbs have been applied, either alone or in combination with other drugs, with the goal of delaying the progression to active MM and restoring the immune system. In this review, we will focus on the main results achieved so far and on the main on-going trials using MoAbs in SMM and NDTEMM.

scholarly journals Stem Cell Therapy and Regenerative Medicine in Autoimmune Diseases

2021 ◽  
Author(s):  
Bhuvaneshwari Sampath ◽  
Priyadarshan Kathirvelu ◽  
Kavitha Sankaranarayanan
Keyword(s):  
Stem Cell ◽  
Immune System ◽  
Regenerative Medicine ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Autoimmune Condition ◽  
Recent Trends

The role of immune system in our body is to defense against the foreign bodies. However, if the immune system fails to recognize self and non-self-cells in our body leads to autoimmune diseases. Widespread autoimmune diseases are rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, and more yet to be added to the list. This chapter discusses about how stem cell-based therapies and advancement of regenerative medicine endow with novel treatment for autoimmune diseases. Furthermore, in detail, specific types of stem cells and their therapeutic approach for each autoimmune condition along with their efficiency to obtain desired results are discussed. Ultimately, this chapter describes the recent trends in treating autoimmune diseases effectively using advanced stem cell research.

scholarly journals Breast Cancer Immunotherapy: An Update

2018 ◽  
Vol 12 ◽  
pp. 117822341877480 ◽  
Author(s):  
Issam Makhoul ◽  
Mohammad Atiq ◽  
Ahmed Alwbari ◽  
Thomas Kieber-Emmons
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Cancer Vaccines ◽  
Checkpoint Inhibitors ◽  
Cancer Surveillance ◽  
Cancer Disease ◽  
Immune Attack

The immune system plays a major role in cancer surveillance. Harnessing its power to treat many cancers is now a reality that has led to cures in hopeless situations where no other solutions were available from traditional anticancer drugs. These spectacular achievements rekindled the oncology community’s interest in extending the benefits to all cancers including breast cancer. The first section of this article reviews the biological foundations of the immune response to different subtypes of breast cancer and the ways cancer may overcome the immune attack leading to cancer disease. The second section is dedicated to the actual immune treatments including breast cancer vaccines, checkpoint inhibitors, monoclonal antibodies, and the “unconventional” immune role of chemotherapy.

The immune system and the immunocompromised patient

2017 ◽  
Author(s):  
Sheila Adam ◽  
Sue Osborne ◽  
John Welch
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune System ◽  
Drug Allergy ◽  
Stem Cell Transplant ◽  
Immunocompromised Patient ◽  
Critically Ill Patient ◽  
Cell Transplant ◽  
Hypersensitivity Reactions ◽  
Nursing Management

This chapter discusses the physiology of the immune system and its related disorders in the critically ill patient. The causes, complications, and management of the immunocompromised patient is discussed at length, detailing the specific nursing management. It also discusses the management of autoimmune disease such as Wegener's granulomatosis and rheumatoid arthritis, and hypersensitivity reactions such as drug allergy and anaphylactic reaction. Cancer is explained in detail, including its complications, specific therapies such as stem cell transplant, and the role of the cancer patient within critical care.

scholarly journals NK cells and CD38: Implication for (Immuno)Therapy in Plasma Cell Dyscrasias

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 768 ◽  
Author(s):  
Renato Zambello ◽  
Gregorio Barilà ◽  
Sabrina Manni ◽  
Francesco Piazza ◽  
Gianpietro Semenzato
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Nk Cells ◽  
Plasma Cell ◽  
Potential Role ◽  
Myeloma Cell ◽  
Initial Reduction ◽  
Plasma Cell Dyscrasias

Immunotherapy represents a promising new avenue for the treatment of multiple myeloma (MM) patients, particularly with the availability of Monoclonal Antibodies (mAbs) as anti-CD38 Daratumumab and Isatuximab and anti-SLAM-F7 Elotuzumab. Although a clear NK activation has been demonstrated for Elotuzumab, the effect of anti-CD38 mAbs on NK system is controversial. As a matter of fact, an initial reduction of NK cells number characterizes Daratumumab therapy, limiting the potential role of this subset on myeloma immunotherapy. In this paper we discuss the role of NK cells along with anti-CD38 therapy and their implication in plasma cell dyscrasias, showing that mechanisms triggered by anti-CD38 mAbs ultimately lead to the activation of the immune system against myeloma cell growth.

scholarly journals A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Mie Oki ◽  
Norihiko Watanabe ◽  
Takayoshi Owada ◽  
Yoshihiro Oya ◽  
Kei Ikeda ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
T Lymphocyte ◽  
Lupus Erythematosus ◽  
Susceptibility Gene ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Immunological Homeostasis ◽  
Deficient Mice

Inhibitory coreceptors are thought to play important roles in maintaining immunological homeostasis, and a defect in the negative signals from inhibitory coreceptors may lead to the development of autoimmune diseases. We have recently identified B and T lymphocyte attenuator (BTLA), a new inhibitory coreceptor expressed on immune cells, and we suggest that BTLA may be involved in the development of autoimmune diseases using BTLA-deficient mice. However, the role of BTLA in the pathogenesis of autoimmune diseases in humans remains unknown. We, therefore, examined the possible association between BTLA and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS) by conducting a case-control genetic association study. We found that 590C single-nucleotide polymorphism (SNP) of BTLA gene was significantly associated with susceptibility to RA, but not to SLE or SS. Furthermore, RA patients bearing this 590C SNP developed the disease significantly earlier than the patients without this allele. We also found that BTLA with 590C allele lacked the inhibitory activity on concanavalin A- and anti-CD3 Ab-induced IL-2 production in Jurkat T cells. These results suggest that BTLA is an RA-susceptibility gene and is involved in the protection from autoimmunity in humans.

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