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

Abstract

BACKGROUND:

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.

• Authors: Zhe Li, Séverine Vermeire, Dominique Bullens, Marc Ferrante, Kristel Van Steen, Maja Noman, Xavier Bossuyt, Paul Rutgeerts, Jan L Ceuppens, Gert Van Assche
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 21 Issue 12 Pg. 2787-96 (Dec 2015) ISSN: 1536-4844 [Electronic] England
• PMID: 26383913 (Publication Type: Journal Article)

Chemical References

• Antigens, CD19
• CD40 Antigens
• CD5 Antigens
• Gastrointestinal Agents
• Tumor Necrosis Factor-alpha
• C-Reactive Protein
• Infliximab

Topics

• Adult
• Antigens, CD19 (blood)
• B-Lymphocyte Subsets (cytology, drug effects)
• B-Lymphocytes (drug effects)
• C-Reactive Protein (drug effects)
• CD40 Antigens (blood, drug effects)
• CD5 Antigens (blood)
• Case-Control Studies
• Female
• Gastrointestinal Agents (blood, pharmacology)
• Humans
• Inflammatory Bowel Diseases (blood, drug therapy)
• Infliximab (blood, pharmacology)
• Male
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)
• Up-Regulation