Fcγ receptor targeting in RA

Toshiyuki Takai,Akiko Tobinai,Masanori Inui,Akira Nakamura,Shota Endo

doi:10.1186/ar3572

Toshiyuki Takai, Akiko Tobinai + Show 3 more

Open Access

https://doi.org/10.1186/ar3572

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Abstract

The activation threshold of cells in the immune system is often tuned by cell surface molecules. Among these, Fc receptors expressed on various hematopoietic cells constitute critical elements for activating or down-modulating immune responses. IgGFc receptors (FcγRs) were originally identified as B cell surface molecules. For more than 40 years, FcγRs have continued to attract the interest of many basic researchers and clinicians due to their intriguing IgG binding ability, which provides a critical link between the humoral and cellular branches of the immune system. Several activating-type FcγRs, which associate with homodimeric Fc receptor common γ subunits, are crucial for the onset and exacerbation of inflammatory diseases. In contrast, a unique inhibitory FcγR, FcγRIIB, plays a critical role in keeping immune cells silent. Murine models for allergic responses and autoimmune diseases including RA illustrate the indispensable roles of activating-type FcγRs and the inhibitory FcγRIIB in the initiation and suppression of inflammation, respectively [1-5]. The ultimate goals of FcγR research are to accomplish our understanding of this molecular family and to delineate novel therapeutic strategies toward the conquest of allergic and autoimmune diseases, infectious diseases, immunodeficiency, transplantation-associated immune disorders, and malignant tumors. Although many lines of evidence indicate that a part of the intravenous Ig (IVIg)-mediated anti-inflammatory effects can be attributable to the blocking of activating-type FcγRs, recent studies have pointed out an indispensable role of FcγRIIB in therapeutic benefits of IVIg in several murine models of inflammatory diseases including RA [6]. In this session, we will give a brief summary of recent knowledge on antibody biomedicine including IVIgto you, in light of exploiting FcγRs as potential therapeutic targets for various inflammatory diseases, along with the comparison withnon-FcγR-mediated mechanisms of IVIg.

Highlights

Acute isolated neurological syndromes, such as optic neuropathy or transverse myelopathy, may cause diagnostic problems since they can be the first presentations in a number of demyelinating disorders including multiple sclerosis (MS) and collagen diseases
tumor necrosis factor (TNF) therapy and demyelinating event: A report indicates that adverse events such as the demyelinating lesion in the brain, optic neuritis, and neuropathy occurred after treatment with anti-TNF alpha therapy in collagen disease, and TNF antagonizing therapy showed worsening in a clinical trial with MS
Believing on the similarities of normal joints in humans and monkeys, we have employed a model of collagen-induced arthritis in Macaca fascicularis in an attempt to evaluate the histological alterations caused by such condition in the extracellular matrix of the articular cartilage

Summary

Introduction

Acute isolated neurological syndromes, such as optic neuropathy or transverse myelopathy, may cause diagnostic problems since they can be the first presentations in a number of demyelinating disorders including multiple sclerosis (MS) and collagen diseases. Acute Serum Amyloid A (A-SAA) is an acute phase protein strongly expressed in rheumatoid arthritis (RA) synovial tissue (ST) critically involved in regulating cell migration and angiogenesis These processes are dependent on downstream interactions between extracellular matrix and cytoskeletal components. Conclusions: These results indicate that Egr-1 contributes to IL-1mediated down-regulation of PPARg expression in OA chondrocytes and suggest that this pathway could be a potential target for pharmacologic intervention in the treatment of OA and possibly other arthritic diseases. Immune cell-derived microparticles (MPs) are present at increased amounts in synovial fluid of rheumatoid arthritis (RA) patients [1] and can activate disease-relevant signalling pathways in RA synovial fibroblasts (SF) [2,3].

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