UCSF

Objectives

Infants exposed to combination therapy with anti-tumor necrosis factor (anti-TNF) agents and thiopurines may exhibit increased infections at 1 year of age compared to unexposed infants. We hypothesized that this increased risk of infection is due to abnormal development of the newborn immune system.

Methods

We immunophenotyped B-cell and T-cell subsets using multiparameter flow cytometry in 1-year-old infants whose mothers were exposed to therapeutic agents for IBD. We analyzed samples from infants exposed to infliximab (IFX) or adalimumab (ADA) monotherapy (IFX/ADA, n = 11), certolizumab pegol (CZP) monotherapy (CZP, n = 4), IFX or ADA plus thiopurine combination therapy (IFX/ADA + IM, n = 4), and CZP plus thiopurine combination therapy (CZP + IM, n = 2).

Results

Percentages of B cells, CD4⁺ T helper cells, T regulatory cells (T_regs), and CD8⁺ cytotoxic T cells, were similar among the groups. Infants exposed to combination therapy (IFX/ADA + IM) exhibited trends toward fewer CD27⁺ B cells, switched memory B cells, plasmablasts, interferon gamma (IFNγ)-producing CD4⁺ and CD8⁺ T cells, and CCR5⁺CD4⁺ T cells, but these did not reach statistical significance.

Conclusions

Multiparameter immunophenotyping of major B-cell and T-cell subsets suggests that the adaptive newborn immune system develops largely unaltered after exposure to combination therapy as compared to anti-TNF monotherapy.