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

## TL;DR

This study shows that CD39+ plasmablasts and their ability to produce adenosine may predict successful infliximab treatment in children with inflammatory bowel disease.

## Contribution

Identifies CD39+ plasmablasts and adenosine production as novel predictors of infliximab response in pediatric IBD.

## Key findings

- IFX responders had higher CD39 expression on plasmablasts and increased adenosine production before treatment.
- Responders showed elevated IL10-producing and α4β7hi plasmablasts compared to nonresponders.
- CD39+ plasmablasts were reduced in inflamed tissues, especially in nonresponders.

## Abstract

IFX responders showed increased CD39 expression on plasmablasts and higher levels of CD39/CD73 co-expression on naïve and memory B cells, along with enhanced ATP degradation and adenosine production before treatment. Response was associated with increased IL10-producing plasmablasts and α4β7hi plasmablasts.

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 plasmablasts were decreased in IFX nonresponders (NRS), we detected 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 adenosine 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, especially 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.