Fc fragments of immunoglobulin G are an inductor of regulatory rheumatoid factor and a promising therapeutic agent for rheumatic diseases

Sidorov, Alexandr; Beduleva, Liubov; Menshikov, Igor; Terentiev, Alexey; Stolyarova, Elena; Abisheva, Nadezhda

doi:10.1016/j.ijbiomac.2016.10.081

Cited by 12 publications

(20 citation statements)

References 8 publications

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“…We have previously shown that the binding of healthy human sera to tanned IgG‐loaded erythrocytes does not change in the presence of IgG 7,8 . On this basis, we concluded that IgG does not carry neoepitopes recognized by regulatory rheumatoid factor 7,8 .…”

Section: Resultsmentioning

confidence: 70%

“…In particular, the classical RF associated with rheumatoid arthritis is specific for cryptic epitopes that are absent from the native IgG molecule and appear as a result of changes in its conformation upon interaction with antigen or heat or chemical treatment 8 . RegRF epitopes are also neoepitopes 7,8 . They are absent from IgG and appear on its papain Fc fragments as a result of the reduction of hinge disulfide bonds 7,8 …”

Section: Introductionmentioning

confidence: 99%

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Comparison of the specificity of rheumatoid factor detected by latex fixation with that of regulatory rheumatoid factor

Beduleva

Sidorov

Semenova

et al. 2020

Clinical Laboratory Analysis

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Section: Resultsmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Comparison of the specificity of rheumatoid factor detected by latex fixation with that of regulatory rheumatoid factor

Beduleva

Sidorov

Semenova

et al. 2020

Clinical Laboratory Analysis

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“…Meanwhile, 10–30% of elderly individuals and 3–5% of the healthy population also express RF in their blood [ 62 ], this may cause false positive result, Hence, more sensitive and specific diagnostic marker for RA is always in need. Contradictorily, it has been reported that the regRF could resist disease progression in RA and in fact, promote remission in autoimmune diseases [ 63 ]. Although regRF is not present in its native IgG form, it is possible to induce its antigenic determinants in the hinge region of Fc fragments of homologous IgG, making it a potential target for RA therapy [ 63 ].…”

Section: Role Of Immune-related Secretory Molecules In Rheumatoid mentioning

confidence: 99%

“…Contradictorily, it has been reported that the regRF could resist disease progression in RA and in fact, promote remission in autoimmune diseases [ 63 ]. Although regRF is not present in its native IgG form, it is possible to induce its antigenic determinants in the hinge region of Fc fragments of homologous IgG, making it a potential target for RA therapy [ 63 ]. Further investigation is also required to evaluate its potential as a diagnostics marker.…”

Section: Role Of Immune-related Secretory Molecules In Rheumatoid mentioning

confidence: 99%

Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development

Yap

Tee

Wong

et al. 2018

Cells

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Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, inflammatory disorder that affects synovial joints, both small and large joints, in a symmetric pattern. This disorder usually does not directly cause death but significantly reduces the quality of life and life expectancy of patients if left untreated. There is no cure for RA but, patients are usually on long-term disease modifying anti-rheumatic drugs (DMARDs) to suppress the joint inflammation, to minimize joint damage, to preserve joint function, and to keep the disease in remission. RA is strongly associated with various immune cells and each of the cell type contributes differently to the disease pathogenesis. Several types of immunomodulatory molecules mainly cytokines secreted from immune cells mediate pathogenesis of RA, hence complicating the disease treatment and management. There are various treatments for RA depending on the severity of the disease and more importantly, the patient’s response towards the given drugs. Early diagnosis of RA and treatment with (DMARDs) are known to significantly improve the treatment outcome of patients. Sensitive biomarkers are crucial in early detection of disease as well as to monitor the disease activity and progress. This review aims to discuss the pathogenic role of various immune cells and immunological molecules in RA. This review also highlights the importance of understanding the immune cells in treating RA and in exploring novel biomarkers.

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“…We have previously published data on eight samples of human Fc fragments. All of them carried epitopes for regRF , but further experiments revealed that some samples of human Fc fragments do not expose epitopes recognized by regRF. The purpose of this study was to elucidate the physicochemical features of the human IgG Fc fragments that are associated with the presence of epitopes recognized by regRF.…”

Section: Introductionmentioning

confidence: 97%

Physicochemical characteristics of human IgG Fc fragments that expose regulatory rheumatoid factor neoepitopes and may show promise as antirheumatic agents

Sidorov

Beduleva

Menshikov

et al. 2020

Biotech and App Biochem

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Previously, we showed that immunoglobulin G (IgG) Fc fragments can expose neoepitopes specific to antibodies that were named regulatory rheumatoid factor (regRF). RegRF confers resistance to experimental autoimmune diseases. Immunization of rats with rat Fc fragments exposing neoepitopes recognized by regRF reduces the symptoms of collagen‐induced arthritis. Therefore, IgG Fc fragments that expose neoepitopes recognized by regRF are promising antirheumatic agents and regRF‐producing lymphocytes are potential therapeutic biotargets. The purpose of this study was to elucidate the physicochemical features of human IgG Fc fragments that are associated with the presence of immunosuppressive neoepitopes recognized by regRF. It was found that the acquisition of neoepitopes recognized by regRF is associated with a reduction of the hinge disulfide bonds and conformational changes in the Fc fragment domains. Alkylation of thiol groups in the hinge leads to loss of the epitopes. Therefore, the neoepitopes recognized by regRF may form directly in the hinge when interchain disulfide bonds are reduced or in the region of the CH2 domain as part of the conformational changes caused by the reduction of the interchain disulfide bonds in the hinge. Species‐specificity studies of neoepitopes recognized by regRF revealed that human and rat neoepitopes recognized by regRF are cross‐reactive.

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Fc fragments of immunoglobulin G are an inductor of regulatory rheumatoid factor and a promising therapeutic agent for rheumatic diseases

Cited by 12 publications

References 8 publications

Comparison of the specificity of rheumatoid factor detected by latex fixation with that of regulatory rheumatoid factor

Comparison of the specificity of rheumatoid factor detected by latex fixation with that of regulatory rheumatoid factor

Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development

Physicochemical characteristics of human IgG Fc fragments that expose regulatory rheumatoid factor neoepitopes and may show promise as antirheumatic agents

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