Adenosine-generating CD39+ plasmablasts predispose to successful infliximab therapy in pediatric IBD

Schnell A, Schwarz B, Schmidt H, Allabauer I, Schuh W, Regensburger A, Rauh M, Wölfle J, Hörning A (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Life Science Alliance Life Science Alliance

Book Volume: 8

Article Number: e202403055

Journal Issue: 6

DOI: 10.26508/lsa.202403055

Abstract

B cells display several immunoregulatory mechanisms including the production of interleukin-10. Ectonucleotidases like CD39 and CD73 influence immune homeostasis by metabolizing eATP and generating immunosuppressive adenosine. The major objective was to examine the expression of those immunoregulatory molecules on B-cell subsets, and, more specifically, to determine their association with an infliximab (IFX) treatment in a pediatric inflammatory bowel disease (IBD) cohort. 42 IBD patients were assessed for IFX response after 12 mo of therapy and compared against 14 healthy controls (HC). Although IL10-producing plas-mablasts were decreased in IFX nonresponders (NRS), we de-tected an up-regulation of CD39 on plasmablasts and increased fractions of CD39/CD73-co-expressing naïve and memory B cells in responding patients (RS). In addition, B cells of responders proved to have superior ATP degradation capacities and aden-osine production before therapy initiation compared with NRS and HC. Moreover, IFX nonresponders had a marked deficiency of α4β7hi plasmablasts, whereas both cohorts had fewer CCR9-expressing plasmablasts. Consequently, CD39⁺ plasmablasts were decreased in biopsies of inflamed mucosal tissues, espe-cially in IFX nonresponders. Our results highlight the regulatory potential of CD39/CD73-expressing B cells in pediatric IBD and suggest CD39⁺ plasmablasts as a potential determinant of a successful immunosuppressive therapy with IFX.

Authors with CRIS profile

Alexander Schnell Department of Paediatrics and Adolescent Medicine Hannah Schmidt Department of Paediatrics and Adolescent Medicine Wolfgang Schuh Department of Molecular Immunology Adrian Regensburger Department of Paediatrics and Adolescent Medicine Manfred Rauh Department of Paediatrics and Adolescent Medicine Joachim Wölfle Lehrstuhl für Kinder- und Jugendmedizin André Hörning Department of Paediatrics and Adolescent Medicine

How to cite

APA:

Schnell, A., Schwarz, B., Schmidt, H., Allabauer, I., Schuh, W., Regensburger, A.,... Hörning, A. (2025). Adenosine-generating CD39+ plasmablasts predispose to successful infliximab therapy in pediatric IBD. Life Science Alliance, 8(6). https://doi.org/10.26508/lsa.202403055

MLA:

Schnell, Alexander, et al. "Adenosine-generating CD39+ plasmablasts predispose to successful infliximab therapy in pediatric IBD." Life Science Alliance 8.6 (2025).

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