title: In vitro observations of T cell responsiveness to recall antigens during tumor necrosis factor-alpha-blocking therapy in patients with ankylosing spondylitis.
abstract: OBJECTIVE
  Anti-tumor necrosis factor-alpha (TNF-alpha) therapy can induce reactivation of tuberculosis and an increase of other infections in patients with ankylosing spondylitis (AS). This raises the question if an alteration of T cell function can be detected by in vitro analysis to identify patients who might be more at risk of acquiring such infectious diseases.
  
  
  METHODS
  We examined peripheral blood from AS patients without history of tuberculosis before and after 10-14 and 24-36 weeks of therapy with adalimumab (n = 8) or infliximab (n = 10). Fresh peripheral blood mononuclear cells were stimulated with cytomegalovirus antigens and with the Mycobacterium tuberculosis antigen purified protein derivative and early secretory antigen target 6. Interferon-gamma production of CD4+ T cells was assessed after in vitro antigen-specific stimulation by intracellular cytokine staining and flow cytometry.
  
  
  RESULTS
  There was no significant change, either decrease or increase, of the T cell response to recall antigens during therapy compared to controls without treatment, if the mean values of all patients treated with adalimumab or infliximab were compared at the given timepoints. However, analysis on the individual patient level of such T cell responses revealed 1 adalimumab-treated patient and 2 infliximab-treated patients with a clear decrease of T cell response during therapy. Longterm analysis indicated that such a decrease of T cell responsiveness is generally transient and reconstituted at the latest after 52 weeks.
  
  
  CONCLUSIONS
  Some patients treated with adalimumab or infliximab showed a decrease of T cell responsiveness, which seems to be transient. These patients in particular might be at risk for intracellular infections.
authors.affiliation: Department of Gastroenterology, Infectiology and Rheumatology, Charité Berlin, Campus Benjamin Franklin, Hindenbergdamm 30, Berlin, Germany. heiner.appel@charite.de
authors.forename: Heiner
authors.initials: H
authors.lastname: Appel
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scheer
authors.forename: Hildrun
authors.initials: H
authors.lastname: Haibel
authors.forename: Peihua
authors.initials: P
authors.lastname: Wu
authors.forename: Inge
authors.initials: I
authors.lastname: Spiller
authors.forename: Henning
authors.initials: H
authors.lastname: Brandt
authors.forename: In-Ho
authors.initials: IH
authors.lastname: Song
authors.forename: Martin
authors.initials: M
authors.lastname: Rudwaleit
authors.forename: Andreas
authors.initials: A
authors.lastname: Thiel
authors.forename: Jochen
authors.initials: J
authors.lastname: Sieper
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000942:Antigens, Bacterial; D000956:Antigens, Viral; D016022:Case-Control Studies; D003587:Cytomegalovirus / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D000069285:Infliximab; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D013167:Spondylitis, Ankylosing / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000942:Antigens, Bacterial; D000956:Antigens, Viral; D004768:Enterotoxins; D014409:Tumor Necrosis Factor-alpha; C031818:enterotoxin B, staphylococcal; D000069285:Infliximab; D000068879:Adalimumab