# Changes in T Lymphocytes and Cytokines After Anti-TNF Treatment in Pediatric Inflammatory Bowel Disease: Association with Response to Pharmacologic Therapy

## TL;DR

The study examines how T lymphocytes and cytokines change after anti-TNF treatment in children with IBD, identifying potential biomarkers for treatment response.

## Contribution

The study identifies specific T lymphocyte populations and cytokine changes associated with short- and long-term response to anti-TNF therapy in pediatric IBD.

## Key findings

- Naïve Tregs are linked to primary response, while activated Tregs correlate with long-term response to anti-TNF drugs.
- INF-γ levels decrease in Crohn’s disease but not in ulcerative colitis after treatment.
- Memory CD8+ Tc2 cells increase in Crohn’s non-responders, and CD4+ Th17 cells in UC non-responders.

## Abstract

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.