title: 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.affiliation: *Clinical Immunology Unit, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; †Division of Gastroenterology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; ‡Laboratory of Pediatric Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; §Department of Bioinformatics-Statistical Genetics, Université of Liège, Liège, Belgium; and ‖Experimental Laboratory Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.forename: Dominique
authors.initials: D
authors.lastname: Bullens
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrante
authors.forename: Kristel
authors.initials: K
authors.lastname: Van Steen
authors.forename: Maja
authors.initials: M
authors.lastname: Noman
authors.forename: Xavier
authors.initials: X
authors.lastname: Bossuyt
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.forename: Jan L
authors.initials: JL
authors.lastname: Ceuppens
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
mesh_terms: D000328:Adult; D018941:Antigens, CD19 / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects; D002097:C-Reactive Protein / Q000187:drug effects; D019013:CD40 Antigens / Q000097:blood / Q000187:drug effects*; D018956:CD5 Antigens / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005765:Gastrointestinal Agents / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood* / Q000188:drug therapy; D000069285:Infliximab / Q000097:blood / Q000494:pharmacology*; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D015854:Up-Regulation
chemical_list: D018941:Antigens, CD19; D019013:CD40 Antigens; D018956:CD5 Antigens; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000069285:Infliximab