Splenic function and IgM-memory B cells in Crohn's disease patients treated with infliximab

Antonio Di Sabatino, M. Manuela Rosado, Paolo Cazzola, Paolo Biancheri, Francesco Paolo Tinozzi, Maria Rita Laera, Laura Cantoro, Alessandro Vanoli, Rita Carsetti, Gino Roberto Corazza

Research output: Contribution to journalArticle

Abstract

Background: Under experimental chronic inflammation, tumor necrosis factor (TNF)-α plays a role in damaging spleen marginal zone. This latter has a crucial function in mounting B cell-dependent immune responses against infections by encapsulated bacteria. In Crohn's disease (CD), a chronic inflammatory disorder where TNF-α is centrally involved, impaired splenic function may increase the susceptibility to bacterial infections. On this basis, we aimed to investigate the influence of anti-TNF therapy on splenic function in CD patients. Methods: Peripheral blood samples were obtained from 15 CD patients before and after treatment with infliximab administered at weeks 0, 2, and 6 at a dose of 5 mg/kg. Counting of erythrocytes with membrane abnormalities (pitted red cells) was used as an indicator of splenic function. Multicolor flow cytometry was performed to analyze circulating B cells. Results: A substantial clinical improvement in 10 of the 15 CD patients was associated with a significant reduction of pitted red cells (from median 6.0% to 3.6%; P <0.01) after 10 weeks of treatment. In responder patients the improvement of splenic function was accompanied by a parallel increase of circulating IgM-memory B cells (from median 6.9% to 13.3%; P <0.005). Splenic function was not ameliorated in nonresponder patients. Conclusions: Splenic function improved in CD patients who responded to infliximab and was accompanied by a concomitant restoration of the IgM-memory B cell pool responsible for the protection against encapsulated bacteria. Restoration of splenic function after infliximab treatment is intriguing and requires further investigation.

Original languageEnglish
Pages (from-to)591-596
Number of pages6
JournalInflammatory Bowel Diseases
Volume14
Issue number5
DOIs
Publication statusPublished - May 2008

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Keywords

  • Hyposplenism
  • Infection
  • Pitted red cell
  • Therapy
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Gastroenterology

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