Changes in T Lymphocytes and Cytokines After Anti-TNF Treatment in Pediatric Inflammatory Bowel Disease: Association with Response to Pharmacologic Therapy
Failure of anti-TNF therapy is a real concern in children with inflammatory bowel disease (IBD) owing to the limited therapeutic arsenal. Anti-TNF drugs modulate the immune response, a key driver of chronic inflammation in IBD. Accordingly, we analyzed changes in the frequency of T-lymphocyte and cytokine levels after 6 weeks of treatment to identify potential biomarkers of response to anti-TNF drugs. We recruited 77 patients under 18 years of age diagnosed with IBD and treated with an anti-TNF drug. Using flow cytometry and multiplex ELISA, we analyzed 31 T-lymphocyte populations and four cytokines. We identified changes in 10 populations of T lymphocytes after 6 weeks of treatment. Naïve Tregs were associated with a primary response to anti-TNF drugs, while activated Tregs were associated with long-term response. Serum INF-γ levels were decreased after anti-TNF treatment in children with Crohn's disease (CD), but not in those with ulcerative colitis (UC). The memory CD8+ Type 2 Cytotoxic T (Tc2) subset increased in non-responders with CD and the CD4+ memory Th17 cells increased in non-responders with UC. These findings could help us to understand the cellular regulation of anti-TNF therapy, to identify children at a higher risk of treatment failure, and, potentially, to develop more personalized therapeutic strategies.
Authors
- Paula Zapata-Cobo (ORCID: https://orcid.org/0000-0003-1907-1709)
- Montserrat Montraveta
- Gemma Pujol‐Muncunill (ORCID: https://orcid.org/0000-0002-9660-5826)
- Ruth García‐Romero
- Sara Salvador‐Martín (ORCID: https://orcid.org/0000-0003-3720-2581)
- Begoña Pérez‐Moneo (ORCID: https://orcid.org/0000-0002-7335-848X)
- Rafael Correa‐Rocha (ORCID: https://orcid.org/0000-0003-3456-9986)
- Marjorie Pion (ORCID: https://orcid.org/0000-0002-6406-747X)
- Sergio Gil-Manso (ORCID: https://orcid.org/0000-0003-2480-3628)
- Lorena Magallares
- Luis A. López‐Fernández
- María Sanjurjo‐Sáez (ORCID: https://orcid.org/0000-0002-8523-3721)
- Marta Velasco Rodríguez‐Belvís (ORCID: https://orcid.org/0000-0003-2844-313X)
- César Sánchez (ORCID: https://orcid.org/0000-0002-1823-0467)
- Óscar Segarra (ORCID: https://orcid.org/0000-0003-2162-1474)
- Diana García‐Tirado
- L M Palomino Pérez (ORCID: https://orcid.org/0000-0002-2441-9311)
- María J. Fobelo (ORCID: https://orcid.org/0000-0002-0546-3966)
- Ana Moreno‐Álvarez
Institutions
- Hospital Sant Joan de Déu Barcelona (ES)
- Hospital Universitario La Paz (ES)
- Hospital General Universitario Gregorio Marañón (ES)
- Hospital Infantil Universitario Niño Jesús (ES)
- Hospital Universitario Miguel Servet (ES)
- Vall d'Hebron Hospital Universitari (ES)
- Complexo Hospitalario Universitario A Coruña (ES)
- Hospital Universitario de Valme (ES)
- Hospital Universitari Germans Trias i Pujol (ES)
- Hospital Universitario Infanta Leonor (ES)
- Deleted Institution
- Universidad de Sevilla (ES)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-04-02
- DOI
- https://doi.org/10.3390/ijms26073323
- Primary Topic
- Inflammatory Bowel Disease
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Comunidad de Madrid
- European Commission
- Consejería de Sanidad, Comunidad de Madrid
- Instituto de Salud Carlos III
- European Regional Development Fund