TY - JOUR
T1 - Circulating and Magnetic Resonance Imaging Biomarkers of Intestinal Fibrosis in Small Bowel Crohn’s Disease
AU - Dillman, Jonathan R.
AU - Tkach, Jean A.
AU - Fletcher, Joel G.
AU - Bruining, David H.
AU - Lu, Aiming
AU - Kugathasan, Subra
AU - Alazraki, Adina L.
AU - Knight-Scott, Jack
AU - Stidham, Ryan W.
AU - Adler, Jeremy
AU - Minar, Phillip
AU - Trapnell, Bruce C.
AU - Bonkowski, Erin L.
AU - Jurrell, Holden
AU - Lopez-Nunez, Oscar
AU - Collins, Margaret H.
AU - Swanson, Scott D.
AU - Fei, Lin
AU - Qian, Lucia
AU - Towbin, Alexander J.
AU - Kocaoglu, Murat
AU - Anton, Christopher G.
AU - Imbus, Rebecca A.
AU - Dudley, Jonathan A.
AU - Denson, Lee A.
N1 - Publisher Copyright:
© The Author(s) 2025. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved.
PY - 2025/5/1
Y1 - 2025/5/1
N2 - Background: 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. Methods: 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. Results: 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). Conclusions: 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.
AB - Background: 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. Methods: 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. Results: 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). Conclusions: 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.
KW - Crohn’s disease
KW - biomarkers
KW - fibrosis
KW - granulocyte-macrophage colony-stimulating factor autoantibodies
KW - magnetic resonance imaging
KW - second harmonic imaging microscopy
UR - https://www.scopus.com/pages/publications/105005192784
U2 - 10.1093/ibd/izae319
DO - 10.1093/ibd/izae319
M3 - Article
C2 - 39853252
AN - SCOPUS:105005192784
SN - 1078-0998
VL - 31
SP - 1380
EP - 1391
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
IS - 5
ER -