Nelson Heather A, Martins Thomas B, Saadalla Abdulrahman, Nandakumar Vijayalakshmi
ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA.
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
Clin Chem Lab Med. 2024 Nov 7;63(4):790-796. doi: 10.1515/cclm-2024-1112. Print 2025 Mar 26.
Early rheumatoid arthritis (RA) detection is crucial for improving patient prognosis. Anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factors (RF) support RA diagnosis but are undetectable in ∼20 % of cases. Recently, antibodies against mutated citrullinated vimentin (anti-MCV) and detection of 14-3-3 eta have emerged with implications for preclinical RA diagnosis and monitoring treatment. The objective of this study was to assess the clinical performance of anti-MCV antibodies and 14-3-3 eta in RA and to compare it to current RA criteria anti-CCP and RF markers, individually and in combination.
A retrospective chart review of 326 subjects submitted for RA serology testing identified 134 RA positive and 192 RA negative disease control individuals. Fifty healthy controls specimens were also included. Performance of anti-MCV and 14-3-3 eta, alone and combined with CCP3.1 and RF, was assessed.
Anti-MCV had a sensitivity of 71 % and a specificity of 92 %. 14-3-3 eta had a sensitivity of 43 % and a specificity of 90 %. In comparison, CCP3.1 and RF displayed a sensitivity of 79 % and 84 % and a specificity of 92 % and 61 %, respectively. ROC curve analysis demonstrated CCP3.1 and anti-MCV had superior diagnostic performance compared to RF and 14-3-3 eta. In our cohort, anti-MCV and 14-3-3 eta failed to identify seronegative RA patients. Different combinations of double antibody positivity increased specificity at the cost of lost sensitivity.
Individually, 14-3-3 eta, anti-MCV and CCP3.1 assays had ≥90 % specificity in diagnosed RA patients, with better sensitivities for anti-MCV and CCP3.1 than 14-3-3 eta. Overall diagnostic performance of anti-MCV was similar to CCP3.1 and RF, all of which outperformed 14-3-3 eta in our cohort.
早期类风湿性关节炎(RA)检测对于改善患者预后至关重要。抗环瓜氨酸肽抗体(抗CCP)和类风湿因子(RF)有助于RA诊断,但在约20%的病例中无法检测到。最近,抗突变波形蛋白瓜氨酸化抗体(抗MCV)和14-3-3η的检测已出现,对临床前RA诊断和治疗监测具有重要意义。本研究的目的是评估抗MCV抗体和14-3-3η在RA中的临床性能,并将其与当前RA标准中的抗CCP和RF标志物单独及联合使用时进行比较。
对326例接受RA血清学检测的受试者进行回顾性病历审查,确定了134例RA阳性和192例RA阴性疾病对照个体。还纳入了50份健康对照样本。评估了抗MCV和14-3-3η单独使用以及与CCP3.1和RF联合使用时的性能。
抗MCV的敏感性为71%,特异性为92%。14-3-3η的敏感性为43%,特异性为90%。相比之下,CCP3.1和RF的敏感性分别为79%和84%,特异性分别为92%和61%。ROC曲线分析表明,与RF和14-3-3η相比,CCP3.1和抗MCV具有更好的诊断性能。在我们的队列中,抗MCV和14-3-3η未能识别血清阴性RA患者。双抗体阳性的不同组合以降低敏感性为代价提高了特异性。
单独来看,14-3-3η、抗MCV和CCP3.1检测在诊断的RA患者中特异性≥90%,抗MCV和CCP3.1的敏感性高于14-3-3η。抗MCV的总体诊断性能与CCP3.1和RF相似,在我们的队列中,它们均优于14-3-3η。