Huang Xianqian, Chen Yong, Peng Yong, Gan Minzhi, Geng Baoqing, Zhu Mengya, Ying Ying
Department of Rheumatology, Ningbo Hwa Mei (No. 2) Hospital, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, Zhejiang 315010, China.
Asian Biomed (Res Rev News). 2022 Apr 29;16(2):89-98. doi: 10.2478/abm-2022-0011. eCollection 2022 Apr.
Ankylosing spondylitis (AS) is a chronic inflammatory arthritic disease, and sacroiliitis, enthesitis, and propensity for sacroiliac and spinal fusion are characteristic pathological features. Interleukin-34 (IL-34) plays a role in the induction and differentiation of osteoclasts. Other inflammatory factors are not directly involved in the induction and differentiation, but play an indirect role by modulating the level of receptor activator of nuclear factor-κB (RANKL) and other molecules during the process of inflammatory bone destruction in AS. However, to our knowledge, the relationship between enthesitis and bone erosion, and IL-34 and RANKL in AS has not yet been elucidated.
To determine the correlation between serum IL-34, RANKL, and disease severity including enthesitis and bone erosion in patients with AS and develop multivariable predictive model.
We conducted a cross-sectional study of 40 patients with AS, compared with 40 patients with osteoarthritis, and 40 healthy volunteers. Their serum levels of IL-34 and RANKL were measured using enzyme-linked immunosorbent assays (ELISAs). Enthesitis and bone erosion were assessed with real-time ultrasonography. Spearman rank correlation coefficients were determined to analyze the relationship between the variables. Multiple logistic regression was used to determine associations and receiver operating characteristic (ROC) curve analyses were conducted to determine the diagnostic performance of cytokine levels.
In patients with AS, serum levels of IL-34 (878.9 ± 116.4 pg/mL) and RANKL (155.6 ± 13.8 pg/mL) were significantly ( < 0.01) higher than those in patients with osteoarthritis (626.6 ± 79.0 and 138.1 ± 15.3 pg/mL, respectively) or a healthy group (612.9 ± 61.1 and 104.9 ± 15.4 pg/mL, respectively). Serum levels of IL-34 were not significantly correlated with the levels of RANKL. In patients with AS, serum levels of IL-34 and RANKL adjusted for age and weight were significantly correlated with enthesitis (0.798, < 0.01; 0.347, < 0.05, respectively) and bone erosion (0.822, < 0.01; 0.368, < 0.05, respectively). The area under the ROC curve (AUC) for the serum levels of IL-34 was 0.995 between patients with AS and healthy individuals. When serum level of IL-34 was >697.1 pg/mL, the sensitivity (SE) was >99% and specificity (SP) was 95.0%. The AUC for IL-34 was 0.982 between patients with AS and patients with osteoarthritis. When serum IL-34 was >688.4 pg/mL, the SE was >99% and SP 85.0%. IL-34 correlation with the number of bone erosions of enthesis was = 0.795, < 0.01. The AUC for serum RANKL was 0.993 between patients with AS and healthy individuals. When serum RANKL was >126.2 pg/mL, the SE was 97.5% and SP 97.5%. The AUC for serum RANKL was 0.798 between patients with AS and patients with osteoarthritis. When serum RANKL was >149.3 pg/mL, the SE was 70% and SP was 80.0%.
In patients with AS, serum levels of IL-34 and RANKL may be useful indicators of enthesitis, especially for bone erosions. IL-34 is associated with AS-associated enthesis damage and is a potential biomarker for predicting subsequent progression in patients with AS.
强直性脊柱炎（AS）是一种慢性炎症性关节炎疾病，骶髂关节炎、附着点炎以及骶髂关节和脊柱融合倾向是其特征性病理表现。白细胞介素-34（IL-34）在破骨细胞的诱导和分化中起作用。其他炎症因子虽不直接参与诱导和分化，但在AS炎症性骨破坏过程中通过调节核因子κB受体激活剂（RANKL）等分子的水平发挥间接作用。然而，据我们所知，AS中附着点炎与骨侵蚀以及IL-34与RANKL之间的关系尚未阐明。
确定AS患者血清IL-34、RANKL与包括附着点炎和骨侵蚀在内的疾病严重程度之间的相关性，并建立多变量预测模型。
我们对40例AS患者、40例骨关节炎患者和40名健康志愿者进行了横断面研究。采用酶联免疫吸附测定（ELISA）法检测他们血清中IL-34和RANKL的水平。通过实时超声评估附着点炎和骨侵蚀情况。采用Spearman等级相关系数分析变量之间的关系。使用多因素逻辑回归确定关联，并进行受试者工作特征（ROC）曲线分析以确定细胞因子水平的诊断性能。
AS患者血清IL-34水平（878.9±116.4 pg/mL）和RANKL水平（155.6±13.8 pg/mL）显著高于骨关节炎患者（分别为626.6±79.0和138.1±15.3 pg/mL）或健康组（分别为612.9±61.1和104.9±15.4 pg/mL）（P<0.01）。血清IL-34水平与RANKL水平无显著相关性。在AS患者中，校正年龄和体重后的血清IL-34和RANKL水平与附着点炎显著相关（分别为0.798，P<0.01；0.347，P<0.05），与骨侵蚀也显著相关（分别为0.822，P<0.01；0.368，P<0.05）。AS患者与健康个体之间血清IL-34水平的ROC曲线下面积（AUC）为0.995。当血清IL-34水平>697.1 pg/mL时，敏感性（SE）>99%，特异性（SP）为95.0%。AS患者与骨关节炎患者之间IL-34的AUC为0.982。当血清IL-34>688.4 pg/mL时，SE>99%，SP为85.0%。IL-34与附着点骨侵蚀数量的相关性为r=0.795，P<0.01。AS患者与健康个体之间血清RANKL的AUC为0.993。当血清RANKL>126.2 pg/mL时，SE为97.5%，SP为97.5%。AS患者与骨关节炎患者之间血清RANKL的AUC为0.798。当血清RANKL>149.3 pg/mL时，SE为70%，SP为80.0%。
在AS患者中，血清IL-34和RANKL水平可能是附着点炎的有用指标，尤其是对于骨侵蚀。IL-34与AS相关的附着点损伤有关，是预测AS患者后续病情进展的潜在生物标志物。
