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Latent Tuberculosis Infection in RA: Current Diagnostic Techniques and Treatment

Latent Tuberculosis Infection in RA: Current Diagnostic Techniques and Treatment

ABSTRACT: The risk of latent tuberculosis infection (LTBI) is greater in patients with rheumatoid arthritis (RA). Regular screening for LTBI is recommended. The Interferon-Gamma Release Assays (IGRAs) overcome some of the disadvantages of the tuberculin skin test. Managing LTBI reduces the risk of progression to active tuberculosis (TB), especially in high-risk groups such as those with RA. Thus, early detection and treatment are the mainstays for decreasing the morbidity and mortality resulting from TB in patients with RA. Isoniazid treatment for patients with LTBI was first recommended for general use in 1965. Rifampin-based regimens might be safer, more effective, and shorter. Patients should be educated about the adverse effects associated with treatment. A 2-step testing approach has been suggested. (J Musculoskel Med. 2011;28:300-309)

The risk of latent tuberculosis infection (LTBI) is far greater in patients with rheumatoid arthritis (RA) than in the general population, and regular screening of these patients for LTBI is recommended. Traditionally, the diagnosis has been based on tuberculin skin test (TST) results as well as on information gathered from the medical history, chest radiography, and physical examination. In recent years, however, newer diagnostic techniques have been developed that may have advantages over the TST.

This 2-part article offers 20 “clinical pearls” to answer key questions about LTBI in patients with RA. In the first part (“Latent tuberculosis infection in RA: The disease and the diagnosis,” The Journal of Musculoskeletal Medicine, July 2011, page 249), we described the traditional diagnostic tests and interpretation of their results. This second part discusses the newer diagnostic techniques, provides a review of the current literature, and describes the current guidelines for treatment and monitoring.

10. What are the newer techniques for the diagnosis of LTBI?

The Interferon-Gamma Release Assays (IGRAs), a newer technique, are based on the principle that sensitized T cells release interferon γ (IFN-γ) when exposed to Mycobacterium tuberculosis antigens.1 The IGRAs include the QuantiFERON-TB Gold (QFT-G) test and the T-SPOT TB (ELISPOT) test. The TST and IGRAs evaluate cell-mediated immunity.

Several studies have addressed the usefulness of IGRAs in patients with RA.2-9 IFN-γ assays that use M tuberculosis–specific region of difference 1 antigens, such as early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10), have advantages over the TST.1,10-12

The QFT-G test was approved in 2001. The T-SPOT TB test, approved more recently, was incorporated into the CDC guidelines for use of IGRAs updated in June 2010. The guidelines recommend the use of IGRAs preferentially in patients who are BCG-vaccinated and those who are unlikely to return for a TST reading.13

IGRAs overcome some of the disadvantages of the TST, as follows:

•  In patients with RA, the results do not change because of their immune status.

•  A patient requires only 1 visit to the health care facility, and the results are available in a day.

•  There is computerized reading of the tests, decreasing the chances of human errors.

•  They have higher specificity—the result is positive only with M tuberculosis,1,10 unlike with the TST.

Limitations include cost and not being widely available. Also, there is a relatively high number of indeterminate results (up to 12%).

11. What is the difference between the QFT-G test and the T-SPOT TB test?

The QFT-G test measures IFN-γ secretion by sensitized T cells after in vitro stimulation with M tuberculosis–specific antigens (ESAT-6, CFP-10, TB7-7) and uses whole blood for measurement. The T-SPOT TB test measures the number of sensitized T cells that secrete IFN-γ and uses peripheral blood mononuclear cells (PBMCs).

12. What are the T-SPOT TB test methods?

Isolated lymphocytes are sensitized to M tuberculosis antigens, and the activated T cells produce IFN-γ. The T-SPOT TB test uses a simplified ELISPOT method to enumerate sensitized T cells by capturing IFN-γ in the vicinity of those cells from which it was secreted.

Washed and counted PBMCs are seeded into 4 microtiter wells where they are exposed to phytohemagglutinin, a mitotic stimulator that indicates cell functionality (positive control); a nil control; and 2 separate panels of M tuberculosis–specific antigens. Secreted cytokine is captured by IFN-γ–specific antibodies in the base of the well and detected with a second antibody that is linked to a color detection agent. Evaluating the number of spots obtained provides a measure of the abundance of M tuberculosis–sensitive effector T cells in the peripheral blood (0 to 4 spots, negative; 5 to 7 spots, equivocal; more than 8 spots, positive).14


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