Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
Department of Laboratory Medicine, OLV Ziekenhuis, Aalst, Belgium.
RMD Open. 2022 Mar;8(1). doi: 10.1136/rmdopen-2021-002099.
Rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) are important biomarkers for diagnosis of rheumatoid arthritis (RA). However, there is poor harmonisation of RF and ACPA assays. The aim of this study was to refine RF and ACPA interpretation across commercial assays.
Six total RF isotype-non-specific assays, 3 RF IgM isotype-specific assays and 9 ACPA immunoglobulin G assays of 13 different companies were evaluated using 398 diagnostic samples from patients with RA and 1073 disease controls.
Using cut-offs proposed by the manufacturer, there was a large variability in diagnostic sensitivity and specificity between assays. Thresholds of antibody levels were determined based on predefined specificities and used to define test result intervals. Test result interval-specific likelihood ratios (LRs) were concordant across the different RF and ACPA assays. For all assays, the LR for RA increased with increasing antibody level. Higher LRs were found for ACPA than for RF. ACPA levels associated with LRs >80 were found in a substantial fraction (>22%) of patients with RA.
Defining thresholds for antibody levels and assigning test result interval-specific LRs allows alignment of clinical interpretation for all RF and ACPA assays.
类风湿因子（RF）和抗瓜氨酸化蛋白/肽抗体（ACPA）是类风湿关节炎（RA）诊断的重要生物标志物。然而，RF 和 ACPA 检测之间的协调性较差。本研究的目的是改进商业检测中 RF 和 ACPA 的解释。
使用来自 398 例 RA 患者和 1073 例疾病对照者的 398 份诊断样本，评估了来自 13 家不同公司的 6 种总 RF 同种型非特异性检测、3 种 RF IgM 同种型特异性检测和 9 种 ACPA 免疫球蛋白 G 检测。
使用制造商建议的截止值，检测之间的诊断灵敏度和特异性存在很大差异。基于预定的特异性确定了抗体水平的阈值，并用于定义测试结果间隔。不同 RF 和 ACPA 检测的测试结果间隔特异性似然比（LR）是一致的。对于所有检测，RA 的 LR 随着抗体水平的增加而增加。ACPA 的 LR 高于 RF。在相当一部分（>22%）RA 患者中发现了与 LR>80 相关的 ACPA 水平。
定义抗体水平的阈值并分配测试结果间隔特异性 LR，可以使所有 RF 和 ACPA 检测的临床解释保持一致。
