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Observational Study
. 2018 Apr 3;9(4):143.
doi: 10.1038/s41424-018-0018-3.

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

Michael G Kattah  1 , Jeffrey M Milush  2 , Trevor Burt  3 , Robert P McCabe Jr  4 , Michael I Whang  5 , Averil Ma  5 , Uma Mahadevan  5
Affiliations
Observational Study

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

Michael G Kattah et al. Clin Transl Gastroenterol. .

Erratum in

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.

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Conflict of interest statement

Guarantor of the article: Michael G. Kattah.

Specific author contributions: U.M. conceived of the study and recruited patients. J.M.M. designed and performed the human flow cytometry experiments. M.G.K. analyzed and interpreted the clinical and flow cytometry data, and performed all statistical analyses. RPM recruited patients and provided critical review of the manuscript. TB aided in experimental design, design of human flow cytometry panels, and provided critical review of the manuscript. M.G.K., M.I.W., and A.M. performed the mouse experiments. M.G.K. and U.M. wrote the manuscript.

Financial support: Crohn’s Colitis Foundation Senior Research Award, Investigator Initiated Study Grant: UCB.

Potential competing interests: Dr. U.M. is a consultant for Takeda, Janssen, and Abbvie and this study was funded by the Crohn’s Colitis Foundation and in part by an investigator initiated study grant from UCB. The remaining authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1. Infants exposed to anti-TNF monotherapy or combination therapy with an anti-TNF agent and a thiopurine immunomodulator exhibited similar immune profiles.
a Spearman's PCA of immunophenotyping and study subjects by drug exposure. Principal components F1, F2, and F3 are shown. Each individual is represented by one data point. The percentage of the variance explained by each principal component is shown on the axis. b–e Median, interquartile ranges, and ranges of frequencies of each cell subset, expressed as a percent of the parent population, are shown. The p-value and q-value displayed in b–e were calculated in the three-group analysis (CZP vs IFX/ADA vs IFX/ADA+ IM)
Fig. 2
Fig. 2. Infants exposed to combination therapy with an anti-TNF agent and an immunomodulator exhibited a trend toward reduced CD27+ B cells, switched memory B cells, plasmablasts, IFNγ-producing CD4+ and CD8+ T cells, and CD4+CCR5+ T cells which did not reach statistical significance.
(a) Ranked p-values for cell subsets in the three-group analysis comparing CZP vs IFX/ADA vs IFX/ADA+IM. (b-g) Median, interquartile ranges, and ranges of frequencies of each cell subset, expressed as a percent of the parent population, are shown. The p-value and q-value displayed in (b-g) were calculated in the three-group analysis. KW-Kruskal Wallis
See this image and copyright information in PMC

References

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