Abstract: In Vitro Observations of T Cell Responsiveness to Recall Antigens During Tumor Necrosis Factor-α-Blocking Therapy in Patients with Ankylosing Spondylitis

In Vitro Observations of T Cell Responsiveness to Recall Antigens During Tumor Necrosis Factor-α-Blocking Therapy in Patients with Ankylosing Spondylitis

HEINER APPEL, REBECCA SCHEER, HILDRUN HAIBEL, PEIHUA WU, INGE SPILLER, HENNING BRANDT, IN-HO SONG, MARTIN RUDWALEIT, ANDREAS THIEL, and JOCHEN SIEPER

ABSTRACT.

Objective. Anti-tumor necrosis factor-a (TNF-a) 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-g 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.

Conclusion. 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. (First Release Oct 1 2007; J Rheumatol 2007;34:2264-70 )

Key Indexing Terms:

ANKYLOSING SPONDYLITIS
T CELL RESPONSE
RECALL ANTIGENS
TUMOR NECROSIS FACTOR-a BLOCKING THERAPY

From the Department of Gastroenterology, Infectiology and Rheumatology, Charité Berlin, Campus Benjamin Franklin, and the Deutsche Rheumaforschungszentrum, Berlin, Germany.

H. Appel, MD; R. Scheer, Technician; H. Haibel, MD; P. Wu, Technician; I. Spiller, MD; H. Brandt, MD; I.H. Song, MD; M. Rudwaleit, MD; J. Sieper, MD, Department of Gastroenterology, Infectiology and Rheumatology, Charité Berlin, Campus Benjamin Franklin; A. Thiel, PhD, Deutsche Rheumaforschungszentrum.

Address reprint requests to Dr. H. Appel, Charité Berlin, Campus Benjamin Franklin, Department of Gastroenterology, Infectiology and Rheumatology, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail: heiner.appel@charite.de.

Accepted for publication July 18, 2007.