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Comparison of an in vitro Tuberculosis Interferon-γ Assay with Delayed-type Hypersensitivity Testing for Detection of Latent Mycobacterium tuberculosis: A Pilot Study in Rheumatoid Arthritis

JEFFREY D. GREENBERG, SOUMYA M. REDDY, SHARI G. SCHLOSS, OLIVER S. KURUCZ, SUSAN J. BARTLETT, STEVEN B. ABRAMSON, and CLIFTON O. BINGHAM III

ABSTRACT.

Objective. Recommendations for screening for latent Mycobacterium tuberculosis (MTB) infection have been proposed but are not well studied in patients with rheumatoid arthritis (RA). We estimated the prevalence of anergy in RA and evaluated different methods to detect MTB exposure.

Methods. This was a prospective pilot study of 61 patients with RA and 42 healthy controls. Tuberculin skin test (TST) antigen, Candida, and tetanus toxoid were injected intradermally using the Mantoux method. Subjects negative for TST returned for a second-step test. Whole-blood interferon-γ (IFN-γ) release to mycobacterial antigens was evaluated with the first-generation QuantiFeron® test (QIFN).

Results. Cutaneous anergy in patients with RA was not significantly different than healthy controls (p = 0.154), and was not affected by disease modifying antirheumatic drugs (p = 0.270). In patients with RA, 16.4% had positive TST with 10 mm cutoff vs 11.9% of controls. Using a 5 mm cutoff, 21.3% of patients with RA were positive, and this increased to 29.5% with a second-step TST. QIFN detected MTB exposure in 18% of patients with RA and 19% of controls (p = 0.897). However, indeterminate QIFN tests were higher in RA patients (11.5%) compared to controls (2.4%), demonstrating a lower sensitivity to detect latent MTB.

Conclusion. Cutaneous anergy may be less common than previously reported in patients with RA. However, the single-step TST and 10 mm cutoff may fail to detect all cases of latent MTB exposure in RA patients. High rates of indeterminate results in QIFN testing suggest that QIFN should not be employed as an alternative, single-screening test in patients with RA. These pilot results require confirmation in larger studies to determine the optimal screening strategy in RA. (First Release Mar 1 2008; J Rheumatol 2008;35:770-5)

Key Indexing Terms:

TUBERCULOSIS
TUBERCULIN TEST
SKIN TESTS
DIAGNOSTIC TECHNIQUES
RHEUMATOID ARTHRITIS

From the Department of Rheumatology, NYU–Hospital for Joint Diseases, New York, New York; and Division of Rheumatology and Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

Supported in part through grants from Amgen, Inc. and Abbott Immunology, and by a grant from New York State ECRIP and the New York University School of Medicine GCRC NCRR-M01-RR00096. Dr. Greenberg was supported by an Arthritis Foundation/American College of Rheumatology Physician Scientist Development Award. Dr. Reddy was funded through a New York State ECRIP grant, grants from Centocor, and an Amgen Fellowship Award. Dr. Bingham was supported through the Goldstein Young Scholar Award of the New York Chapter Arthritis Foundation and through an Arthritis Foundation Arthritis Investigator Award.

J.D. Greenberg, MD, MPH; S.M. Reddy, MD; S.G. Schloss, MD; O.S. Kurucz, MD; S.B. Abramson, MD, Department of Rheumatology, NYU–Hospital for Joint Diseases; S.J. Bartlett, PhD, Division of Rheumatology; C.O. Bingham III, MD, Division of Rheumatology and Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins Medical Institutions.

Address reprint requests to Dr. C.O. Bingham III, 5200 Eastern Avenue, Mason F. Lord Building, Center Tower Room 404, Baltimore, MD 21224. E-mail: Clifton.bingham@jhmi.edu

Accepted for publication December 21, 2007.