Laboratory of Molecular and Cell Immunology, Department of Immunology and Cell Biology, Udmurt State University, Izhevsk, Russian Federation.
Laboratory of Biocompatible Materials, Udmurt Federal Research Center UB RAS, Izhevsk, Russian Federation.
J Clin Lab Anal. 2022 Feb;36(2):e24187. doi: 10.1002/jcla.24187. Epub 2021 Dec 24.
Previously, we identified a regulatory rheumatoid factor (regRF), the production of which provides rats with resistance to collagen-induced arthritis (CIA). Immunization with conformers of IgG Fc fragments carrying epitopes specific to regRF reduces symptoms of CIA. The aim of this study was to determine whether there is a link between regRF levels and rheumatoid arthritis (RA) activity in humans in order to assess the potential of regRF as a therapeutic biotarget in RA. The variability of rheumatoid factor (RF) specificities present in the blood of RA patients was also studied.
The regRF were studied in RA patients with active disease and in remission. Variability in the specificities of RF associated with RA was studied by concurrent inhibition of RF latex fixation by variants of modified IgG.
Patients in remission had regRF levels higher than in healthy subjects. The regRF in remission was characterized by tight binding to its antigen, as in healthy subjects. The regRF levels in patients with active RA varied dramatically, and regRF binding to its antigen was weak. The exacerbation of Still's disease coincided with low regRF levels and affinity, while an improvement in patient condition was associated with an increase in regRF levels and affinity. The RF specific to RA, which was detected by the RF latex-fixation method, was a nonhomogeneous population of antibodies that included RF to lyophilized IgG, to IgG immobilized on polystyrene, and to rabbit IgG.
Stimulating regRF production might enable improved RA therapy.
此前,我们鉴定了一种调控性类风湿因子(regRF),其产生可使大鼠对胶原诱导性关节炎(CIA)产生抗性。用携带针对 regRF 的表位的 IgG Fc 片段的构象体免疫可减轻 CIA 的症状。本研究旨在确定人类 regRF 水平与类风湿关节炎(RA)活动之间是否存在关联,以评估 regRF 作为 RA 治疗性生物靶标的潜力。还研究了 RA 患者血液中存在的 RF 特异性的变异性。
研究了活动期和缓解期 RA 患者的 regRF。通过用修饰的 IgG 变体同时抑制 RF 乳胶固定,研究与 RA 相关的 RF 特异性的变异性。
缓解期患者的 regRF 水平高于健康受试者。缓解期的 regRF 与其抗原的结合紧密,与健康受试者相同。活动期 RA 患者的 regRF 水平差异很大,且其与抗原的结合较弱。斯蒂尔病的恶化与低水平和低亲和力的 regRF 相关,而患者病情的改善与高水平和高亲和力的 regRF 相关。通过 RF 乳胶固定法检测到的 RA 特异性 RF 是一种非均相的抗体群体,包括对冻干 IgG、固定在聚苯乙烯上的 IgG 以及兔 IgG 的 RF。
刺激 regRF 产生可能会改善 RA 治疗。