Th1/Th17 cytokine signatures correlate with Crohn’s disease activity in a 54‑week cohort of patients treated with adalimumab

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with a relapsing-remitting course. Cytokine dysregulation plays a central role in its pathogenesis, and biological therapies-such as anti‑TNFα agents, vedolizumab, and anti‑IL‑23 monoclonal antibodies-have improved disease control. However, variability in therapeutic response underscores the need for biomarkers to support personalized treatment strategies. A longitudinal study was conducted in 26 patients with clinical‑remission/mild‑activity CD who were treated with adalimumab over 54 weeks. Serum samples were collected at baseline, week 14, and week 54. Eighteen cytokines were quantified using high‑sensitivity Luminex MAP technology. TNFα values were excluded due to drug interference. Clustering and PERMANOVA analyses were used to explore cytokine profiles and their association with disease activity. Four cytokine clusters were identified: Th1‑like, Th2‑like, Th17‑like, and a mixed inflammatory profile including IL‑1β, IL‑2, IL‑12, IL‑21, and IL‑23. Significant reductions in CDAI, C‑reactive protein (CRP), and fibrinogen were observed during treatment. IL‑2, IL‑10, and CCL20 levels increased significantly in patients with active CD (CDAI ≥ 150). Th1 and Th17 signatures were positively correlated with disease activity. Serum assessment of Th1 (IL‑1β, IL‑7) and Th17 (GM‑CSF) signatures generated ROC curves with an AUC of 0.795, compared with CRP (AUC = 0.686) and fibrinogen (AUC = 0.774). Serum cytokine profiling reveals immunological heterogeneity in CD patients treated with adalimumab and may serve as an exploratory biomarker of disease activity and therapeutic response; however, these findings are hypothesis generating and require validation in larger, independent cohorts before clinical applicability can be established.

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Journal
Biomedicine & Pharmacotherapy
Published
2026-05-29
DOI
https://doi.org/10.1016/j.biopha.2026.119508
Primary Topic
Inflammatory Bowel Disease
Type
article
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0.00

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article

Th1/Th17 cytokine signatures correlate with Crohn’s disease activity in a 54‑week cohort of patients treated with adalimumab

Fernando Gomollón, Iván Guerra, Laura Sempere, Patricia De Castro-Martinez et al.
Biomedicine & Pharmacotherapy
Inflammatory Bowel Disease
article

Th1/Th17 cytokine signatures correlate with Crohn’s disease activity in a 54‑week cohort of patients treated with adalimumab

Fernando Gomollón, Iván Guerra, Laura Sempere, Patricia De Castro-Martinez, Jorge Monserrat, Francisco Mesonero, C. García-Montero, Óscar Fraile-Martínez, M A Ortega Ortega, Melchor Álvarez‐Mon, Joaquín Hinojosa, I Vera, M D Martín-Arranz, Ignacio Marín-Jiménez, Javier P. Gisbert, Diego L. Boaru, José L. Cabriada, Luis G. Guijarro, Valle García-Sánchez, Manuel Barreiro-de Acosta, Cristina Alba, Ana M. Gómez-Lahoz, Luis Bujanda, María Chaparro, Marisa Iborra
article en

Abstract

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with a relapsing-remitting course. Cytokine dysregulation plays a central role in its pathogenesis, and biological therapies-such as anti‑TNFα agents, vedolizumab, and anti‑IL‑23 monoclonal antibodies-have improved disease control. However, variability in therapeutic response underscores the need for biomarkers to support personalized treatment strategies. A longitudinal study was conducted in 26 patients with clinical‑remission/mild‑activity CD who were treated with adalimumab over 54 weeks. Serum samples were collected at baseline, week 14, and week 54. Eighteen cytokines were quantified using high‑sensitivity Luminex MAP technology. TNFα values were excluded due to drug interference. Clustering and PERMANOVA analyses were used to explore cytokine profiles and their association with disease activity. Four cytokine clusters were identified: Th1‑like, Th2‑like, Th17‑like, and a mixed inflammatory profile including IL‑1β, IL‑2, IL‑12, IL‑21, and IL‑23. Significant reductions in CDAI, C‑reactive protein (CRP), and fibrinogen were observed during treatment. IL‑2, IL‑10, and CCL20 levels increased significantly in patients with active CD (CDAI ≥ 150). Th1 and Th17 signatures were positively correlated with disease activity. Serum assessment of Th1 (IL‑1β, IL‑7) and Th17 (GM‑CSF) signatures generated ROC curves with an AUC of 0.795, compared with CRP (AUC = 0.686) and fibrinogen (AUC = 0.774). Serum cytokine profiling reveals immunological heterogeneity in CD patients treated with adalimumab and may serve as an exploratory biomarker of disease activity and therapeutic response; however, these findings are hypothesis generating and require validation in larger, independent cohorts before clinical applicability can be established.

Biomedicine & PharmacotherapyVol. 200
University of the Basque Country (ES), Universidad de Alcalá (ES), Hospital Universitario La Paz (ES), Hospital General Universitario Gregorio Marañón (ES), Hospital Clínico San Carlos (ES), Hospital Universitari i Politècnic La Fe (ES), Hospital Universitario Puerta de Hierro Majadahonda (ES), Hospital de Galdakao (ES), Hospital Universitario Reina Sofía (ES), Instituto Ramón y Cajal de Investigación Sanitaria (ES), Hospital Universitario de La Princesa (ES), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES), Instituto de Investigación Sanitaria Aragón (ES), Hospital General Universitario de Alicante Doctor Balmis (ES), Instituto de Investigación Sanitaria de Santiago (ES), Hospital Virgen del Camino (ES), Hospital Universitario Ramón y Cajal (ES), Instituto de Investigación Sanitaria La Fe (ES), Universidad Autónoma de Madrid (ES)
Comunidad de Madrid, Instituto de Salud Carlos III, Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
Good health and well-being
Openalex Percentile: Top 6%
Inflammatory Bowel Disease
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