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

✍ Scribed by 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

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 308 KB
• Volume: 14
• Category: Article
• ISSN: 1078-0998
• DOI: 10.1002/ibd.20374

✦ Synopsis

Background: Under experimental chronic inflammation, tumor necrosis factor (TNF)-␣ 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-␣ 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 Ͻ 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 Ͻ 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.