title: Adalimumab treatment in Crohn's disease does not induce early changes in regulatory T cells.
abstract: OBJECTIVE
  Anti-TNF-α antibodies has been suggested to modulate regulatory T cell (Treg) percentages in rheumatoid arthritis, but results from studies of Crohn's disease (CD) are conflicting. We investigated dynamic changes of circulating Tregs in CD during treatment with the anti-TNF-α-antibody adalimumab (Humira®, Abbott Laboratories A/S, Emdrupvej 28C, DK-2100 Copenhagen).
  
  
  METHODS
  Blood samples from 26 CD patients were analysed using flow cytometry before and 1 and 26 weeks after initiation of adalimumab treatment to determine the percentage of Tregs among CD4+ T cells.
  
  
  RESULTS
  In spite of a significant decline in disease activity scores and biochemical markers of inflammation, during the first week of treatment, we did not observe early modulating effects of adalimumab on Treg percentages. However, we found a long-term increase in Treg percentages in responders who had low Treg percentages (<5%) at baseline (p = 0.04). Treg percentage was inversely associated with disease activity (CD activity index or CDAI) (Spearman's rank correlation, ρ = -0.47, p = 0.02). High Treg percentages among CD4+ T cells at baseline predicted clinical response to adalimumab.
  
  
  CONCLUSIONS
  Adalimumab treatment did not induce early modulatory effects on Treg percentage, even in responders. This finding suggests that adalimumab does not have a direct or selective effect on Tregs. However, Treg percentage was associated with disease activity and high Treg percentage predicted response to adalimumab.
authors.affiliation: Department of Medicine V (Hepatology and Gastroenterology), Gastro-Immuno Research Laboratory (GIRL), Aarhus University Hospital, Denmark. andedige@rm.dk
authors.forename: Anders
authors.initials: A
authors.lastname: Dige
authors.forename: Christian Lodberg
authors.initials: CL
authors.lastname: Hvas
authors.forename: Bent
authors.initials: B
authors.lastname: Deleuran
authors.forename: Jens
authors.initials: J
authors.lastname: Kelsen
authors.forename: Mia
authors.initials: M
authors.lastname: Bendix-Struve
authors.forename: Jens Frederik
authors.initials: JF
authors.lastname: Dahlerup
authors.forename: Jørgen
authors.initials: J
authors.lastname: Agnholt
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D002097:C-Reactive Protein; D000068879:Adalimumab