In vitro observations of T cell responsiveness to recall antigens during tumor necrosis factor-alpha-blocking therapy in patients with ankylosing spondylitis.
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.
Appel
Heiner
H
Department of Gastroenterology, Infectiology and Rheumatology, Charité Berlin, Campus Benjamin Franklin, Hindenbergdamm 30, Berlin, Germany. heiner.appel@charite.de
Scheer
Rebecca
R
Haibel
Hildrun
H
Wu
Peihua
P
Spiller
Inge
I
Brandt
Henning
H
Song
In-Ho
IH
Rudwaleit
Martin
M
Thiel
Andreas
A
Sieper
Jochen
J
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*
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