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Anti-Tumor Necrosis Factor Therapy Restores Peripheral Blood B-cell Subsets and CD40 Expression in Inflammatory Bowel Diseases.

AbstractBACKGROUND:
Anti-tumor necrosis factor (TNF) therapy has become a standard therapy for severe inflammatory bowel diseases (IBD), but its effect on B lymphocytes is largely unexplored. In this study we investigated peripheral blood B cells, B-cell subsets, and CD40 expression in patients with IBD before and during anti-TNF therapy with infliximab (IFX).
METHODS:
Blood was taken from healthy controls (n = 52) and patients with active IBD before (n = 46) and/or during anti-TNF therapy (n = 55). B-cell markers were detected by immunofluorescent staining and FACS analysis. Patients were classified as responders or nonresponders to anti-TNF therapy.
RESULTS:
We found a numerical deficiency of circulating CD19 B cells, a lower activation state (CD40 expression) and lower proportions of CD5 B cells and IgMIgDCD27 preswitched memory cells among B cells in active patients with IBD before IFX therapy compared with healthy controls. IFX treatment increased CD19 B-cell numbers as well as the proportions of named B-cell subsets in responders but not in nonresponders. IFX more effectively upregulated CD40 expression in responders than in nonresponders. Restoration of B cells correlated with the biological response to therapy (C-reactive protein). Trough serum levels of IFX correlated with the number of B cells during therapy.
CONCLUSIONS:
A lower number of circulating B cells, a low CD40 expression, and a decrease in the proportion of CD5 and in the preswitched memory subset characterize active IBD. Restoration of these abnormalities correlates with the clinical response to anti-TNF therapy. The mechanism for this effect on B cells should be further explored.
AuthorsZhe Li, Séverine Vermeire, Dominique Bullens, Marc Ferrante, Kristel Van Steen, Maja Noman, Xavier Bossuyt, Paul Rutgeerts, Jan L Ceuppens, Gert Van Assche
JournalInflammatory bowel diseases (Inflamm Bowel Dis) Vol. 21 Issue 12 Pg. 2787-96 (Dec 2015) ISSN: 1536-4844 [Electronic] United States
PMID26383913 (Publication Type: Journal Article)

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