title: Serum immune-activation potency and response to anti-TNF-α therapy in Crohn's disease.
abstract: OBJECTIVE
  To study whether immune-activation stage in serum of adult Crohn's disease (CD) patients correlates with disease activity and with treatment response to anti-tumor necrosis factor-α (TNF-α) therapy.
  
  
  METHODS
  Serum samples were obtained from 15 adult CD patients introduced to anti-TNF-α therapy. The individual stage of immune activation was studied applying our new in vitro assay, in which target cells (donor derived peripheral blood mononuclear cells) were cultured with patient serum and the T-cell activation induced by the patient serum was studied using a panel of markers for effector [interferon γ (IFNγ), interleukin (IL)-5] and regulatory T-cells [forkhead transcription factor 3 (FOXP3) and glucocorticoid-induced tumour necrosis factor receptor (GITR)]. The endoscopic disease activity was assessed with the Crohn's disease endoscopic index of severity (CDEIS) before and 3 mo after therapy with an anti-TNF-α agent.
  
  
  RESULTS
  Low induction of FOXP3 and GITR in target cells cultured in the presence of patient serum was associated with high disease activity i.e. CDEIS assessed before therapy (r = -0.621, P = 0.013 and r = -0.625, P = 0.013, respectively). FOXP3 expression correlated inversely with pre-treatment erythrocyte sedimentation rate (r = -0.548, P = 0.034). Low serum induced FOXP3 (r = -0.600, P = 0.018) and GITR (r = -0.589, P = 0.021) expression and low IFNγ secretion from target cells (r = -0.538, P = 0.039) associated with treatment response detected as a decrease in CDEIS.
  
  
  CONCLUSIONS
  The immune-activation potency in the patient serum prior to anti-TNF-α therapy reflected intestinal inflammation and the therapeutic response.
authors.affiliation: Division of Gastroenterology, Hospital for Children and Adolescents and Helsinki University Central Hospital, University of Helsinki, Helsinki, FIN-00029, Finland. hanne.rintamaki@helsinki.fi
authors.forename: Hanne
authors.initials: H
authors.lastname: Rintamäki
authors.forename: Taina
authors.initials: T
authors.lastname: Sipponen
authors.forename: Harri-M
authors.initials: HM
authors.lastname: Salo
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
authors.forename: Kaija-Leena
authors.initials: KL
authors.lastname: Kolho
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D005243:Feces / Q000737:chemistry; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood / Q000235:genetics / Q000276:immunology; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000097:blood / Q000235:genetics / Q000276:immunology; D015848:Interleukin-5 / Q000097:blood / Q000235:genetics / Q000276:immunology; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000097:blood / Q000235:genetics / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; C508599:IL5 protein, human; D020381:Interleukin-17; D015848:Interleukin-5; D039841:Leukocyte L1 Antigen Complex; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma