S. Holm Nielsen, PhD, Biomedicine and Biotechnology, Technical University of Denmark, Lyngby, and ImmunoScience, Nordic Bioscience, Biomarkers and Research, Herlev, Denmark;
A. Stahly, MD, E.H. Regner, MD, PhD, K.A. Kuhn, MD, PhD, Department of Medicine, Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
J Rheumatol. 2022 Dec;49(12):1335-1340. doi: 10.3899/jrheum.220142. Epub 2022 Jun 15.
Chronic inflammatory arthritis is a hallmark of axial spondyloarthritis (axSpA), where coexistence of Crohn disease (CD) is prominent. We investigated the association between biomarkers of collagen degradation in healthy controls (HCs) and in patients with axSpA, CD, and CD and axSpA overlap (CD-axSpA), with the aim to investigate the ability of the biomarkers to identify patients with CD-axSpA.
Patients with axSpA who fulfilled Assessment of Spondyloarthritis international Society criteria (n = 13), had biopsy-proven CD (n = 14), had CD-axSpA (n = 10), and HCs (n = 11) undergoing standard-of-care colonoscopies were included in the study. The collagen biomarkers measuring type III, IV, VI and X collagen (C3M, C4M, C6M, and C10C, respectively) were measured in plasma samples from all subject groups. Statistical analysis was performed using an ANCOVA adjusted for age, an area under the receiver-operating characteristic (AUROC) curve analysis, and Spearman correlation.
C4M was significantly higher in patients with CD-axSpA overlap compared to axSpA, CD, and HCs (all < 0.001). In an AUROC analysis, C4M showed a complete separation between the patients with CD-axSpA overlap compared to HC, axSpA and CD with an area under the curve (AUC) = 1.00 ( < 0.001). No differences were found between the patient groups for C3M, C6M, and C10C. No correlations were found between the collagen biomarkers and C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Simple Clinical Colitis Activity Index, or Harvey-Bradshaw Index scores.
Degradation of type IV collagen quantified by C4M showed a complete separation of patients with CD-axSpA overlap, compared to axSpA, CD, and HCs, and indicates excessive collagen degradation and epithelial turnover. This biomarker could potentially be used to identify patients affected by both manifestations and to guide treatment decisions.
慢性炎症性关节炎是中轴型脊柱关节炎（axSpA）的标志，其中克罗恩病（CD）共存较为突出。我们研究了健康对照组（HCs）和 axSpA、CD 和 CD 与 axSpA 重叠（CD-axSpA）患者中胶原蛋白降解生物标志物的相关性，旨在研究这些生物标志物识别 CD-axSpA 患者的能力。
本研究纳入了符合脊柱关节炎国际协会评估标准的 axSpA 患者（n=13）、经活检证实的 CD 患者（n=14）、CD-axSpA 患者（n=10）和接受标准护理结肠镜检查的 HCs（n=11）。所有受试者组的血浆样本中均检测了 III、IV、VI 和 X 型胶原蛋白的生物标志物（分别为 C3M、C4M、C6M 和 C10C）。使用调整年龄的协方差分析（ANCOVA）、受试者工作特征（ROC）曲线下面积（AUROC）分析和 Spearman 相关分析进行统计分析。
CD-axSpA 重叠患者的 C4M 明显高于 axSpA、CD 和 HCs 组（均<0.001）。在 ROC 分析中，C4M 完全区分了 CD-axSpA 重叠患者与 HC、axSpA 和 CD 患者，曲线下面积（AUC）=1.00（<0.001）。C3M、C6M 和 C10C 在患者组之间无差异。胶原蛋白生物标志物与 C 反应蛋白、巴斯强直性脊柱炎疾病活动指数、简单临床结肠炎活动指数或 Harvey-Bradshaw 指数评分之间无相关性。
通过 C4M 定量测定的 IV 型胶原蛋白降解，CD-axSpA 重叠患者与 axSpA、CD 和 HCs 患者完全分离，表明胶原蛋白过度降解和上皮细胞更新。该生物标志物可能有助于识别同时存在两种表现的患者，并指导治疗决策。
