Department of Rheumatology, Saint-Joseph University, Beirut, Lebanon.
Department of Rheumatology, Hotel-Dieu de France Hospital, Beirut, Lebanon.
Front Immunol. 2019 Mar 26;10:574. doi: 10.3389/fimmu.2019.00574. eCollection 2019.
Axial spondyloarthritis (axSpA) is often diagnosed late due to the non-specific nature of its main symptom [chronic back pain (CBP)] and to the paucity of diagnostic markers, particularly in regions with low HLA-B27 prevalence, such as the Middle-East. We tested the performance of IgG4 and IgA anti-CD74 antibodies as an early diagnostic marker for axSpA, compared with the performance of HLA-B27, in Lebanon. Sera of axSpA patients diagnosed by the rheumatologist and also fulfilling the imaging arm of the ASAS criteria (patients) and of blood donors (BD) (controls) were analyzed for HLA-B27, IgG4 and IgA anti-CD74, blinded to clinical characteristics. Receiver Operating Characteristic curves were constructed to identify an optimal cut-off point for anti-CD74 antibodies. Diagnostic properties were calculated (sensitivity, specificity, positive, and positive predictive values (PPV, NPV), Likelihood ratios) for each marker. Forty-nine axSpA patients and 102 BD were included in the final analysis. IgA anti-CD74 correlated poorly with axSpA (Area Under the Curve (AUC) 0.657), whereas IgG4 anti-CD74 had a good discriminative value (AUC 0.837). Respectively, for HLA-B27, IgG4 anti-CD74, and the combination of both, we found a sensitivity of 33-92-33%, specificity of 96-79-98%, PPV 80-68-89%, NPV 75-95-75%, and LR+ 8.2-4.4-16.5. IgG4 anti-CD 74 were positive in 88% of HLA-B27 negative axSpA patients, and correlated with BASDAI. In this first study in a population with low HLA-B27 prevalence, IgG4 anti-CD74 antibodies combined with HLA-B27 showed higher diagnostic value than HLA-B27 alone for early axSpA. IgG4 anti-CD74 should be considered for further evaluation as an early axSpA diagnostic marker in future dedicated research, particularly in patients with CBP.
中轴型脊柱关节炎（axSpA）常因主要症状（慢性腰痛，CBP）的非特异性和缺乏诊断标志物而导致诊断延迟，尤其是在 HLA-B27 流行率较低的中东地区。我们在黎巴嫩，以 HLA-B27 为对照，检测 IgG4 和 IgA 抗 CD74 抗体作为 axSpA 的早期诊断标志物的性能。由风湿病医生诊断为 axSpA 且符合 ASAS 影像学标准的患者（患者）和献血者（BD）（对照）的血清进行 HLA-B27、IgG4 和 IgA 抗 CD74 分析，分析时对临床特征设盲。构建受试者工作特征曲线以确定抗 CD74 抗体的最佳截断值。计算每个标志物的诊断特性（敏感性、特异性、阳性和阳性预测值（PPV、NPV）、似然比）。最终分析纳入 49 例 axSpA 患者和 102 例 BD。IgA 抗 CD74 与 axSpA 相关性较差（曲线下面积[AUC]0.657），而 IgG4 抗 CD74 具有良好的鉴别价值（AUC 0.837）。分别对于 HLA-B27、IgG4 抗 CD74 和两者的组合，我们发现敏感性为 33-92-33%，特异性为 96-79-98%，PPV 为 80-68-89%，NPV 为 75-95-75%，LR+ 为 8.2-4.4-16.5。88%的 HLA-B27 阴性 axSpA 患者 IgG4 抗 CD74 阳性，与 BASDAI 相关。在 HLA-B27 流行率较低的人群中进行的第一项研究中，与单独 HLA-B27 相比，IgG4 抗 CD74 抗体联合 HLA-B27 对早期 axSpA 具有更高的诊断价值。在未来的专门研究中，IgG4 抗 CD74 应被视为 axSpA 的早期诊断标志物，特别是对 CBP 患者。
