Comparison of Two Gamma Interferon Release Assays and Tuberculin Skin Testing for Tuberculosis Screening in a Cohort of Patients with Rheumatic Diseases Starting Anti-Tumor Necrosis Factor Therapy

Abstract

Gamma interferon release assays (IGRAs) are increasingly used for latent Mycobacterium tuberculosis infection (LTBI) screening in patients with rheumatic diseases starting anti-tumor necrosis factor (anti-TNF) therapies. We compared the performances of two IGRAs, an enzyme-linked immunospot release assay (T-SPOT.TB) and an enzyme-linked immunosorbent assay (QuantiFERON-TB Gold In Tube [QFT-GIT]), to that of tuberculin skin testing (TST) for LTBI screening of 157 consecutive rheumatic patients starting anti-TNF therapies. Among 155 patients with valid results, 58 (37%) were positive by TST, 39 (25%) by T-SPOT.TB assay, and 32 (21%) by QFT-GIT assay. IGRAs were associated more strongly with at least one risk factor for tuberculosis (TB) than TST. Risk factors for a positive assay included chest X-ray findings of old TB (TST), advanced age (both IGRAs), origin from a country with a high TB prevalence, and a positive TST (T-SPOT.TB assay). Steroid use was negatively associated with a positive QFT-GIT assay. The agreement rate between IGRAs was 81% (kappa rate ‫؍‬ 0.47), which was much higher than that observed between an IGRA and TST. If positivity by either TST or an IGRA was required for LTBI diagnosis, then the rate of LTBI would have been 46 to 47%, while if an IGRA was performed only for TST-positive patients, the respective rate would have been 11 to 17%. In conclusion, IGRAs appear to correlate better with TB risk than TST and should be included in TB screening of patients starting anti-TNF therapies. In view of the high risk of TB in these patients, a combination of one IGRA and TST is probably more appropriate for LTBI diagnosis.The accurate diagnosis of latent Mycobacterium tuberculosis infection (LTBI) is critical for patients with various autoimmune diseases who are starting anti-tumor necrosis factor (anti-TNF) therapies, since the majority of tuberculosis (TB) cases developing in this population are due to LTBI reactivation (1.5 to 4 times increased risk) (18)(19)(20). Traditional methods for LTBI diagnosis, such as the tuberculin skin test (TST), have well-known limitations regarding their sensitivity and specificity for LTBI diagnosis (18)(19)(20). Over the last decade, different gamma interferon (IFN-␥) release assays (IGRAs) have been approved for LTBI diagnosis (13). These assays detect IFN-␥ secreted by peripheral mononuclear cells after in vitro stimulation with specific M. tuberculosis antigens not present in the M. bovis bacillus Calmette-Guérin (BCG) vaccine, either by enzyme-linked immunosorbent assay (ELISA) (QuantiFERON-TB Gold [QFT-G] and QuantiFERON-TB Gold In Tube [QFT-GIT] assays; Cellestis Limited, Carnegie, Victoria, Australia) or by enzyme-linked immunospot assay (T-SPOT.TB assay; Oxford Immunotec, Oxford, United Kingdom). Newer techniques for the diagnosis of LTBI or active TB based on the secretion of IFN-␥ after specific stimulation with specific M. tuberculosis antigens, such as the heparinbinding hemagglutinin (HBHA), have also shown promising results (28).Although there have b...

Evaluating Indeterminate Interferon‐γ–Release Assay Results in Patients With Chronic Inflammatory Diseases Receiving Immunosuppressive Therapy

“…Overall, our results are in general agreement with previous studies that have examined rates of indeterminate tests and observed rates as low as 1.3-13.4% (20)(21)(22)(23). The indeterminate rates differ between studies and may reflect the nature of the study population (i.e., variable activity of underlying rheumatic disease), geographic origin, sample size, and standards of concomitant immunosuppressive therapy use.…”

High Incidence of Tuberculosis Infection in Rheumatic Diseases and Impact for Chemoprophylactic Prevention of Tuberculosis Activation during Biologics Therapy

“…It has been demonstrated that IGRAs are superior to TST in identifying LTBI in immunosuppressed and BCG-vaccinated populations (14)(15)(16)(17)20). In this study, we found that the T-SPOT.TBpositive rate was slightly higher than the TST-positive rate (46.5% versus 37.6%) in patients with rheumatic diseases before biologics treatment, which may indicate higher sensitivity in immunosuppressed patients.…”

Testy IGRA w Diagnostyce Zakażenia Prątkami Gruźlicy w Wybranych Sytuacjach Klinicznych

“…Istotną kwestią, która pozostaje do wyjaśnienia, jest pytanie, czy testy IGRA należy stosować zamiast, czy w połączeniu z próbą tuberkulinową. W róż-nych krajach proponuje się odmienne wytyczne [6,7,21,22].…”

“…W Hiszpanii, Wielkiej Brytanii, Kanadzie i we Włoszech preferuje się strategię diagnostyki LTBI dwuetapowo: wstępne badanie TST, po nim dopiero IGRA, w przypadkach gdy TST jest dodatnie. We Francji TST i IGRA stosuje się natomiast wymiennie [7,21,22]. Australijskie wytyczne nie oferują żadnego konkretnego zalecenia do stosowania testów IGRA, niektórzy proponują wykonanie testu IGRA po negatywnym wyniku próby tuberkulinowej, inni zastępują TST testami IGRA [6].…”