Usefulness of Enzyme-Linked Immunospot Assay (Elispot) Compared to Tuberculin Skin Testing for Latent Tuberculosis Screening in Rheumatic Patients Scheduled for Anti-Tumor Necrosis Factor Treatment

DIMITRIOS VASSILOPOULOS, NIKOLAOS STAMOULIS, EMILIA HADZIYANNIS, and ATHANASIOS J. ARCHIMANDRITIS

ABSTRACT.

Objective. Treatment with tumor necrosis factor (TNF) antagonists in patients with rheumatic diseases has been associated with increased rates of tuberculosis due to reactivation of latent Mycobacterium tuberculosis (MTb) infection (LTBI). Diagnosis of LTBI is based mainly on the tuberculin skin test (TST), which has certain limitations.

Methods. We compared the TST with an enzyme-linked immunospot interferon-g (IFN-g) release assay (Elispot; T SPOT^® TB) for the diagnosis of LTBI in 70 patients with various rheumatic diseases starting treatment with anti-TNF agents. All patients underwent a standard initial evaluation for LTBI including clinical examination, chest radiograph, and standard TST. Freshly isolated peripheral blood mononuclear cells were stimulated ex vivo with MTb-specific antigens (ESAT-6 and CFP10), and IFN-g-producing cells were counted (Elispot assay).

Results. Twenty-seven patients (38.6%) were TST+ and 16 were Elispot+ (22.8%). The overall level of agreement between the 2 tests was 72.8%, being much higher in patients who were TST- (39/43, 90.6%) than in those who were TST+ (12/27, 44.4%). Discordant results were observed in 19 patients (27.1%). Among TST- patients (n = 43), 4 were Elispot+ (9.3%); we also identified 15 Elispot- patients among 27 TST+ patients (55.6%). Multivariate analysis showed that a history of bacillus Calmette-Guérin (BCG) vaccination was associated with TST+/Elispot- discordant results (p = 0.01), whereas steroid use was linked to TST-/Elispot+ discordant results (p = 0.04).

Conclusion. Elispot assay is a useful test for diagnosis of LTBI in rheumatic patients scheduled for anti-TNF therapy and identification of patients with false-positive TST results due to previous BCG vaccination. (J Rheumatol First Release Mar 15 2008)

Key Indexing Terms:

TUMOR NECROSIS FACTOR INHIBITORS
RHEUMATOID ARTHRITIS
TUBERCULOSIS
SPONDYLOARTHROPATHIES
TUBERCULIN TEST
DIAGNOSIS

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From the 2nd Department of Medicine, Hippokration General Hospital, Athens University School of Medicine, Athens, Greece.

D. Vassilopoulos, MD, Assistant Professor of Medicine, Rheumatology; N. Stamoulis, MD; E. Hadziyannis, MD, Instructor in Clinical Microbiology; A.J. Archimandritis, MD, Professor of Medicine, Chairman, 2nd Department of Medicine, Hippokration General Hospital, Athens University School of Medicine.

Address reprint requests to Dr. D. Vassilopoulos, 2nd Department of Medicine, Hippokration General Hospital, Athens University School of Medicine, 114 Vass. Sophias Ave., 115 27 Athens, Greece. E-mail: dvassilop@med.uoa.gr

Accepted for publication December 6, 2007.