Dillman Jonathan R, Tkach Jean A, Fletcher Joel G, Bruining David H, Lu Aiming, Kugathasan Subra, Alazraki Adina L, Knight-Scott Jack, Stidham Ryan W, Adler Jeremy, Minar Phillip, Trapnell Bruce C, Bonkowski Erin L, Jurrell Holden, Lopez-Nunez Oscar, Collins Margaret H, Swanson Scott D, Fei Lin, Qian Lucia, Towbin Alexander J, Kocaoglu Murat, Anton Christopher G, Imbus Rebecca A, Dudley Jonathan A, Denson Lee A
Department of Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Inflamm Bowel Dis. 2025 May 12;31(5):1380-1391. doi: 10.1093/ibd/izae319.
We previously identified circulating and MRI biomarkers associated with the surgical management of Crohn's disease (CD). Here we tested associations between these biomarkers and ileal resection inflammation and collagen content.
Fifty CD patients undergoing ileal resection were prospectively enrolled at 4 centers. Circulating CD64, extracellular matrix protein 1 (ECM1), GM-CSF autoantibodies (GM-CSF Ab), and fecal calprotectin were measured by ELISA. Ileal 3-dimensional magnetization transfer ratio (3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, diffusion-weighted intravoxel incoherent motion (IVIM), and the simplified magnetic resonance index of activity (sMaRIA) were measured by MRI. Ileal resection specimen acute inflammation was graded, and collagen content was measured quantitatively using second harmonic imaging microscopy. Associations between biomarkers and ileal collagen content were tested.
Median (interquartile range [IQR]) age was 19.5 (16-33) years. We observed an inverse relationship between ileal acute inflammation and collagen content (r = -0.39 [95% confidence interval {CI}: -0.61, -0.10], P = .008). Most patients (33 [66%]) received biologics, with no variation in collagen content with treatment exposures. In the univariate analysis, CD64, GM-CSF Ab, fecal calprotectin, and sMaRIA were positively associated with acute inflammation and negatively associated with collagen content (P < .1). The multivariable model for ileal collagen content (R2 = 0.31 [95% CI: 0.11, 0.52]) included log CD64 (β = -.27; P = .19), log ECM1 (β = .47; P = .06), log GM-CSF Ab (β = -.15; P = .01), IVIM f (β = .29, P = .10), and IVIM D* (β = 1.69, P = .13).
Clinically available and exploratory circulating and MRI biomarkers are associated with the degree of inflammation versus fibrosis in CD ileal resections. With further validation, these biomarkers may be used to guide medical and surgical decision-making for refractory CD.
我们之前已确定与克罗恩病（CD）手术治疗相关的循环和MRI生物标志物。在此，我们测试了这些生物标志物与回肠切除术后炎症及胶原蛋白含量之间的关联。
前瞻性纳入4个中心的50例接受回肠切除术的CD患者。通过ELISA检测循环中的CD64、细胞外基质蛋白1（ECM1）、GM-CSF自身抗体（GM-CSF Ab）和粪便钙卫蛋白。通过MRI测量回肠三维磁化传递率（3D MTR）、改良Look-Locker反转恢复（MOLLI）T1弛豫、扩散加权体素内不相干运动（IVIM）以及简化磁共振活动指数（sMaRIA）。对回肠切除标本的急性炎症进行分级，并使用二次谐波成像显微镜定量测量胶原蛋白含量。测试生物标志物与回肠胶原蛋白含量之间的关联。
中位（四分位间距[IQR]）年龄为19.5（16 - 33）岁。我们观察到回肠急性炎症与胶原蛋白含量呈负相关（r = -0.39[95%置信区间{CI}：-0.61，-0.10]，P = 0.008）。大多数患者（33例[66%]）接受了生物制剂治疗，胶原蛋白含量在不同治疗暴露情况下无差异。在单变量分析中，CD64、GM-CSF Ab、粪便钙卫蛋白和sMaRIA与急性炎症呈正相关，与胶原蛋白含量呈负相关（P < 0.1）。回肠胶原蛋白含量的多变量模型（R2 = 0.31[95% CI：0.11，0.52]）包括log CD64（β = -0.27；P = 0.19）、log ECM1（β = 0.47；P = 0.06）、log GM-CSF Ab（β = -0.15；P = 0.01）、IVIM f（β = 0.29，P = 0.10）和IVIM D*（β = 1.69，P = 0.13）。
临床可用及探索性的循环和MRI生物标志物与CD回肠切除术中炎症与纤维化程度相关。经过进一步验证，这些生物标志物可用于指导难治性CD的药物和手术决策。
