Department of Immunopathology, Sanquin Research, Amsterdam, Netherlands
Department of Immunopathology, Sanquin Research, Amsterdam, Netherlands.
RMD Open. 2024 Aug 20;10(3):e004172. doi: 10.1136/rmdopen-2024-004172.
Rheumatoid arthritis (RA) is characterised by the presence of autoantibodies, among which those targeting the constant region of immunoglobulin G (IgG), called rheumatoid factors (RF). Despite this link, RFs can also be found in other disorders and the healthy population, which hampers its use as a diagnostic tool. We recently showed that a subset of RA-derived RFs target a distinct epitope on the IgG-Fc, a feature that is currently not used in the clinic.
We determined immunoglobulin M (IgM)-RF levels specific against an RA-associated epitope (using our engineered next-generation RF antigen 'T3-17') in a prospective cohort of 475 patients with seropositive (for IgM-RF or aCCP) arthralgia that were followed for 5 years or until the development of arthritis.
The presence of RFs targeting T3-17 was more strongly associated with progression to arthritis in comparison to traditional RF measurements. Within the group of patients positive for T3-17 RF the risk of arthritis development was increased as compared with wild-type RF, HR=3.2 (95% CI 2.4 to 4.3) vs HR=2.2 (95% CI 1.7 to 3.0). Predictive power of T3-17 RF was improved in combination with aCCP titres, HR=6.4 (4.7-8.7) vs HR=5.1 (3.9-6.8). This combination performed better than aCCP detection on its own.
The detection of disease-specific RF is feasible and seems to improve the diagnostic power of RF and should be considered to be implemented in the clinic.
类风湿关节炎（RA）的特征是存在自身抗体，其中针对免疫球蛋白 G（IgG）恒定区的抗体称为类风湿因子（RF）。尽管存在这种联系，但 RF 也存在于其他疾病和健康人群中，这阻碍了它作为诊断工具的应用。我们最近表明，RA 衍生的 RF 亚群针对 IgG-Fc 上的一个独特表位，而目前在临床上尚未使用这一特征。
我们在一个前瞻性队列中，对 475 名血清阳性（针对 IgM-RF 或 aCCP）的关节痛患者进行了针对与 RA 相关表位的免疫球蛋白 M（IgM）-RF 水平（使用我们工程化的下一代 RF 抗原“T3-17”）的测定，这些患者随访了 5 年或直至发生关节炎。
与传统 RF 测量相比，针对 T3-17 的 RF 的存在与进展为关节炎的相关性更强。在 T3-17 RF 阳性的患者组中，与野生型 RF 相比，关节炎发展的风险增加，HR=3.2（95%CI 2.4 至 4.3）vs HR=2.2（95%CI 1.7 至 3.0）。T3-17 RF 与 aCCP 滴度联合使用时，预测能力得到改善，HR=6.4（4.7 至 8.7）vs HR=5.1（3.9 至 6.8）。这种联合检测比单独使用 aCCP 检测的效果更好。
疾病特异性 RF 的检测是可行的，似乎可以提高 RF 的诊断能力，应该考虑在临床上实施。
