Anti-TNF-alpha loss of response is associated with a decreased percentage of FoxP3+ T cells and a variant NOD2 genotype in patients with Crohn’s disease

Anti-TNF-α therapies interact with the tolerogenic response in patients with Crohn’s disease, modulating inflammation. However, drug levels and the genetic background may affect this interaction.

Fifty-seven patients were included. Thirty-nine patients (68.4 %) were receiving non-intensified biologic therapy whereas 18 patients (31.6 %) were under an intensified biologic schedule due to loss of response. Eleven intensified patients (61.1 %) showed a variant NOD2 genotype vs 9 on non-intensified biologics (23 %, p < 0.01). Percentage of FoxP3+ T cells and serum free anti-TNF-α levels were significantly higher in patients with a wild-type vs variant NOD2 genotype, either under non-intensified or intensified schedule. Increasing amounts of infliximab significantly increased the expression of FoxP3+ T cells and anti-TNF-α levels in the supernatant from wild-type NOD2 patients cultured cells whereas the induction of FoxP3+ T cells and anti-TNF-α levels in the supernatant from variant NOD2 patients cultured cells were significantly lower. TNF-α and IL-10 showed a correlation with the FoxP3+ T cell population percentage and serum levels of anti-TNF-α, irrespective of NOD2 genotype. Eight variant NOD2 patients (66.6 %) vs 4 wild-type NOD2 patients (8.8 %) showed a perianal phenotype (p = 0.01). A significant reduction of the percentage of FoxP3+ T cells and serum levels of anti-TNF-α was observed in patients with the associated perianal disease.