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

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Physicochemical characteristics of human IgG Fc fragments that expose regulatory rheumatoid factor neoepitopes and may show promise as antirheumatic agents.
Biotechnology and Applied Biochemistry ( IF 3.2 ) Pub Date : 2019-11-08 , DOI: 10.1002/bab.1849
Alexandr Sidorov _{1,

2} , Liubov Beduleva _{1,

2,

3} , Igor Menshikov _{1,

2,

3} , Alexey Terentiev _{1,

2} , Igor Cherepanov ₄

Affiliation

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.

中文翻译：

人IgG Fc片段的理化特性，可暴露类风湿因子新表位，并有望作为抗风湿药。

以前，我们显示免疫球蛋白G（IgG）Fc片段可以暴露特异于称为调节性类风湿因子（regRF）的抗体的新表位。RegRF赋予对实验性自身免疫性疾病的抵抗力。用暴露于regRF识别的新表位的大鼠Fc片段对大鼠进行免疫可减少胶原诱导的关节炎症状。因此，暴露regRF识别的新表位的IgG Fc片段是有希望的抗风湿药，而产生regRF的淋巴细胞是潜在的治疗性生物靶标。这项研究的目的是阐明与regRF识别的免疫抑制新表位的存在有关的人IgG Fc片段的物理化学特征。发现由regRF识别的新表位的获得与铰链二硫键的减少和Fc片段结构域的构象变化有关。铰链中硫醇基的烷基化导致表位的损失。因此，当链间二硫键还原或在CH区域时，regRF识别的新表位可能直接在铰链中形成₂结构域是由铰链中链间二硫键减少引起的构象变化的一部分。regRF识别的新表位的物种特异性研究表明，regRF识别的人和大鼠新表位是交叉反应的。

更新日期：2019-11-08

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