Anti-TNF and thiopurine therapy in pregnant IBD patients does not significantly alter a panel of B-cell and T-cell subsets in 1-year-old infants

Clin Transl Gastroenterol. 2018 Apr 3;9(4):143. doi: 10.1038/s41424-018-0018-3.

Abstract

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 (Tregs), 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.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / therapeutic use
  • Adult
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • B-Lymphocyte Subsets / metabolism*
  • Certolizumab Pegol / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunologic Factors / therapeutic use*
  • Immunophenotyping
  • Infant
  • Infections / immunology
  • Inflammatory Bowel Diseases / drug therapy*
  • Infliximab / therapeutic use
  • Male
  • Mercaptopurine / therapeutic use
  • Mice, Inbred C57BL
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Prenatal Exposure Delayed Effects*
  • Prospective Studies
  • Risk Factors
  • T-Lymphocyte Subsets / metabolism*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Anti-Inflammatory Agents
  • Immunologic Factors
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Mercaptopurine
  • Adalimumab
  • Certolizumab Pegol