Apical fibrobullous lung disease in spondyloarthritis patients with biologic DMARDs indication.

OBJECTIVE: The rate of pleuroparenchymal involvement in patients with SpA varies widely, from 0% to 85%. The most common form is apical fibrobullous disease (AFLD). The aim of this study was to determine the incidence of AFLD and associated factors in SpA patients under and/or planned to start biologic DMARDs (bDMARDs) therapy. METHODS: The records of 3021 SPA patients registered with HUR-BIO who had indication of bDMARDs between 2010 and 2021 were scanned. The study included 2489 patients with at least one chest radiograph (X-ray). Patient demographics, comorbidities, laboratory data, bDMARDs used, baseline DASs, and purified protein derivative and/or QuantiFERON test results before initiation of bDMARDs were recorded. RESULTS: Of the 2489 patients, 36 (1.4%) were found to have AFLD by X-ray and/or CT. The mean disease duration was 11.7 (7.1) years. Patients with AFLD were more likely to be male [28 (77.8%) vs 1321 (53.9%), P = 0.004], older [56.3 (10.5) years vs 44.8 (11.4) years, P < 0.001], heavy smokers [27 (79.4%) vs 1468 (60.9%), P = 0.028] and have had longer disease duration [17. 7 (9.7) years vs 11.6 (7) years, P = 0.001]. QuantiFERON positivity was higher in the AFLD group [9 (36%) vs 309 (16.1%), P = 0.013]. While treatment with adalimumab was less preferred in those with AFLD, treatment with etanercept was more frequently preferred. CONCLUSION: As the radiological findings of AFLD can be confused with those of tuberculosis, special attention should be paid to differentiating between tuberculosis and the disease in males and in patients who have had long disease duration.

Comparing the diagnostic performance of QuantiFERON-TB Gold Plus with QFT-GIT, T-SPOT.TB and TST: a systematic review and meta-analysis.

BACKGROUND: QuantiFERON-TB Gold Plus (QFT-Plus) is an important test that has emerged in recent years for detecting TB infection. We conducted a review to compare the sensitivity, specificity and positive rate of QFT-Plus with that of QuantiFERON-TB Gold In-Tube (QFT-GIT), T-cell spot of tuberculosis assay (T-SPOT.TB) and Tuberculin test (TST). METHODS: PubMed and Embase were searched, without language restrictions, from 1 January 2015 to 31 March 2022 using "Mycobacterium tuberculosis Infections" and "QuantiFERON-TB-Plus" as search phrases. We estimated the sensitivity from studies of patients with active tuberculosis, specificity from studies of populations with very low risk of TB exposure, and positive rate from studies of high-risk populations. The methodological quality of the eligible studies was assessed, and a random-effects model meta-analysis was used to determine the risk difference (RD). We assessed the pooled rate by using a random-effects model. This study was registered in PROSPERO (CRD 42021267432). RESULTS: Of 3996 studies, 83 were eligible for full-text screening and 41 were included in the meta-analysis. In patients with active TB, the sensitivity of QFT-Plus was compared to that of QFT-GIT and T-SPOT.TB, respectively, and no statistically differences were found. In populations with a very low risk of TB exposure, the specificity of QFT-Plus was compared with that of QFT-GTI and T-SPOT.TB, respectively, and no statistically differences were found. Two studies were eligible to compare the specificity of the QFT-Plus test with that of the TST test, and the pooled RD was 0.12 (95% CI 0.02 to 0.22). In high-risk populations, 18 studies were eligible to compare the positive rate of the QFT-Plus test with that of the QFT-GIT test, and the pooled RD was 0.02 (95% CI 0.01 to 0.03). The positive rate of QFT-Plus was compared with that of T-SPOT.TB and TST groups, and no statistically differences were found. CONCLUSIONS: The diagnostic performance of QFT-Plus was similar to that of QFT-GIT and T-SPOT.TB, but was slightly more specific than TST.

Comparison of interferon-gamma production between TB1 and TB2 tubes of QuantiFERON-TB Gold Plus: a meta-analysis.

OBJECTIVES: CD8 T-cells play an important role in interferon-gamma (IFN-γ) production as a host defense against tuberculosis (TB) infection. Therefore, QuantiFERON-TB Gold Plus (QFT-Plus) was developed by adding a TB2 tube beside the TB1 tube. This study aimed to compare and analyze the difference in IFN-γ production between the two tubes in general and specific populations. CONTENT: PubMed, Web of Science, and EBSCO were searched for studies reporting IFN-γ production levels in the TB1 and TB2 tubes. Statistical analysis was performed using RevMan 5.3. SUMMARY: A total of 17 studies met the inclusion criteria. The IFN-γ production in the TB2 tube was statistically higher than that in the TB1 tube (mean difference (MD)=0.02, 95 % confidence interval (95 % CI): 0.01-0.03). Further subgroup analysis in specific populations revealed that the MD of IFN-γ production between the TB2 and TB1 tubes was significantly higher in active TB subjects than in latent TB infection (LTBI) subjects (MD=1.13, 95 % CI: 0.49-1.77, and MD=0.30, 95 % CI: 0.00-0.60, respectively). A similar finding was found in immune-mediated inflammatory disease subjects, but not statistically significant. Interestingly, IFN-γ production capacity was lower in active TB subjects than in LTBI subjects in each of the TB1 and TB2 tubes. OUTLOOK: This study is the first to systematically compare IFN-γ production between the TB1 and TB2 tubes. The IFN-γ production was higher in the TB2 tube than in the TB1 tube, representing the host's CD8 T-cell response magnitude to TB infection.

Do the drug doses of conventional synthetic DMARDs used for the treatment of biologic/targeted-synthetic DMARDs naive rheumatoid arthritis patients affect QuantiFERON-TB Gold Plus test results?

We aimed to obtain the effects of immunosuppressive doses on the QuantiFERON-TB Gold Plus (QFT-Plus) test results in Rheumatoid Arthritis (RA) patients. Besides this, the impact of the TB2 tube in QFT-Plus test was also investigated. This study included RA patients registered to HURBIO and were screened via QFT-Plus test for latent tuberculosis between January 2018 and March 2021, before the initiation of treatment of biologic/targeted-synthetic disease modifying anti-rheumatismal drugs (b/ts-DMARDs). Patients using methotrexate ≥ 10 mg or leflunomide (any dose) or steroids (≥ 7.5 mg prednisolone) at the time of QFT-Plus test were classified as the "high dose" group and the rest of the patients constituted the "low dose" group. The study included 534 RA patients; 353 [66.1%] in the high-dose group and 181 [33.9%] in the low-dose group. While QFT-Plus test was positive in 10.5% (37/353) patients in the high-dose group, it was positive in 20.4% (37/181) patients in the low-dose group (p < 0.001). The percentage of QFT-Plus indeterminate results were similar (around 2%) in both groups. The contribution of the TB2 tube to QFT-Plus test positivity was 6.89%. During a median (inter-quartile range) follow-up period of 23 (7-38) months under treatment of b/ts-DMARDs, latent TB reactivation was not observed. Primer active tuberculosis disease developed in two patients. Positive test results of Interferon-Gamma Release Assays (IGRAs) could decrease as immunosuppressive treatment doses increase in patients with RA and addition of the TB2 tube could increase test sensitivity.

Comparison of the Standard E TB-Feron ELISA and QuantiFERON-TB Gold PLUS assays: the advantageous use of whole recombinant protein antigens for latent tuberculosis diagnosis.

The laboratory diagnosis of latent tuberculosis is often performed using interferon-gamma release assays. Here, we compared two enzyme-linked immunosorbent assay-based interferon-gamma release assays, namely, the newly developed Standard E TB-Feron enzyme-linked immunosorbent assay (STFE) and the QuantiFERON-TB Gold PLUS assay (QFT-GP), using samples from 155 participants. The STFE is based on using whole EAST6 and CFP10 recombinant antigens for latent tuberculosis diagnosis. The participants were classified into four groups and screened using both assays per the manufacturers' instructions. Thereafter, two statistical analyses were conducted to compare the obtained results. First, the STFE results were compared with the QTF-GP results (used as the gold standard) to calculate the total concordance, sensitivity, and specificity of STFE. Second, positivity and negativity concordances were calculated to differentiate healthy participants from participants with tuberculosis. The STFE showed 97% and 94% sensitivity and specificity, respectively. Furthermore, its positivity and negativity concordances were 91% and 98%, respectively. These results indicate the coordinated clinical performance of STFE in detecting latent tuberculosis and its improved performance in targeting tuberculosis-infected participants. Based on the comparison of the latent tuberculosis diagnostic abilities of STFE and QFT-GP, we establish the suitability and superior performance of STFE as a diagnostic tool.

Prevalence of Latent Tuberculosis Infection among Patients Undergoing Regular Hemodialysis in Disenfranchised Communities: A Multicenter Study during COVID-19 Pandemic.

Background and Objectives: Due to their weakened immune response, hemodialysis (HD) patients with latent tuberculosis infection (LTBI) are at higher risk for active tuberculosis (TB) disease and are more subject to patient-to-patient transmission within dialysis units. Consequently, current guidelines advocate screening these patients for LTBI. To our knowledge, the epidemiology of LTBI in HD patients has never been examined before in Lebanon. In this context, this study aimed to determine LTBI prevalence among patients undergoing regular HD in Northern Lebanon and to identify potential factors associated with this infection. Notably, the study was conducted during the COVID-19 pandemic, which is likely to have catastrophic effects on TB and increase the risk of mortality and hospitalization in HD patients. Materials and Methods: A multicenter cross-sectional study was carried out in three hospital dialysis units in Tripoli, North Lebanon. Blood samples and sociodemographic and clinical data were collected from 93 HD patients. To screen for LTBI, all patient samples underwent the fourth-generation QuantiFERON-TB Gold Plus assay (QFT-Plus). Multivariable logistic regression analysis was used to identify the predictors of LTBI status in HD patients. Results: Overall, 51 men and 42 women were enrolled. The mean age of the study population was 58.3 ± 12.4 years. Nine HD patients had indeterminate QFT-Plus results and were therefore excluded from subsequent statistical analysis. Among the remaining 84 participants with valid results, QFT-Plus was positive in 16 patients, showing a positivity prevalence of 19% (95% interval for p: 11.3%, 29.1%). Multivariable logistic regression analysis showed that LTBI was significantly associated with age [OR = 1.06; 95% CI = 1.01 to 1.13; p = 0.03] and a low-income level [OR = 9.29; 95% CI = 1.62 to 178; p = 0.04]. Conclusion: LTBI was found to be prevalent in one in five HD patients examined in our study. Therefore, effective TB control measures need to be implemented in this vulnerable population, with special attention to elderly patients with low socioeconomic status.

Comparing the Diagnostic Performance of QuantiFERON-TB Gold Plus to Other Tests of Latent Tuberculosis Infection: A Systematic Review and Meta-analysis.

BACKGROUND: We conducted a review to compare the sensitivity, specificity, reproducibility, and predictive ability of QuantiFERON-TB Gold Plus (QFT-Plus) with that of QuantiFERON-TB Gold In-Tube (QFT-GIT; QIAGEN, Hilden, Germany) and other latent tuberculosis infection (LTBI) tests. METHODS: We searched MEDLINE, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from January 2013 through May 2020. We included studies comparing QFT-Plus with at least one other LTBI test. We estimated sensitivity from studies of patients with active tuberculosis, and specificity from studies of healthy individuals with low risk of LTBI. Three independent reviewers evaluated eligibility, extracted data, and assessed risk of bias. RESULTS: Compared with QFT-GIT, the sensitivity of QFT-Plus in patients with active TB was 1.3% higher (95% confidence interval [CI], -0.3% to 2.9%); in 2 studies of patients with very low probability of LTBI, the specificity was 0.9% lower (95% CI, -2.4% to 0.6%). These differences were not statistically significant. The agreement between QFT-Plus and QFT-GIT was high, with a pooled Cohen's kappa statistic of 0.83 (95% CI, 0.79 to 0.88). The reproducibility of QFT-GIT and QFT-Plus was similarly poor. All participants in the studies to estimate sensitivity were aged ≥15 years, and only 6 were people living with human immunodeficiency virus. We found no studies to assess predictive ability. CONCLUSIONS: QFT-Plus has diagnostic performance that is very similar to that of QFT-GIT. Further studies are needed to assess the sensitivity of QFT-Plus in immunocompromised patients and younger children before concluding if this new version offers advantages.

Longitudinal Mycobacterium tuberculosis-Specific Interferon Gamma Responses in Ethiopian HIV-Negative Women during Pregnancy and Postpartum.

Pregnancy may influence cellular immune responses to Mycobacterium tuberculosis. We investigated M. tuberculosis-specific interferon-γ responses in women followed longitudinally during pregnancy and postpartum. Interferon-γ levels (stimulated by M. tuberculosis antigens [TB1 and TB2] and mitogen included in the QuantiFERON-TB Gold Plus assay) were measured in blood from pregnant HIV-negative women identified from a prospective cohort at Ethiopian antenatal care clinics. Longitudinal comparisons included women without active tuberculosis (TB) with M. tuberculosis-triggered interferon-γ responses of ≥ 0.20 IU/ml, sampled on two and/or three occasions (1st/2nd trimester, 3rd trimester, and 9 months postpartum). Among 2,093 women in the source cohort, 363 met inclusion criteria for longitudinal comparisons of M. tuberculosis-stimulated interferon-γ responses. Median M. tuberculosis-triggered interferon-γ concentrations were higher at 3rd than those at the 1st/2nd trimester (in 38 women with samples available from these time points; TB1: 2.8 versus 1.6 IU/ml, P = 0.005; TB2: 3.3 versus 2.8 IU/ml, P = 0.03) and postpartum (in 49 women with samples available from these time points; TB1: 3.1 versus 2.2 IU/ml, P = 0.01; TB2: 3.1 versus 2.3 IU/ml, P = 0.03). In contrast, mitogen-stimulated interferon-γ levels were lower at 3rd than those at 1st/2nd trimester (in 32 women with samples available from these time points: 21.0 versus 34.9 IU/ml, P = 0.02). Results were similar in 22 women sampled on all 3 occasions. In HIV-negative women, M. tuberculosis-stimulated interferon-γ responses were higher during the 3rd trimester than those at earlier stages of pregnancy and postpartum, despite decreased mitogen-triggered responses. These findings suggest increased M. tuberculosis-specific cellular responses due to dynamic changes of latent TB infection during pregnancy.

Plasma interferon-γ-inducible protein 10 (IP-10) levels correlate with disease severity and paradoxical reactions in extrapulmonary tuberculosis.

BACKGROUND: With 1.5 million deaths worldwide in 2018, tuberculosis (TB) remains a major global public health problem. While pulmonary TB (PTB) is the most common manifestation, the proportion of extrapulmonary TB (EPTB) is increasing in low-burden countries. EPTB is a heterogeneous disease entity posing diagnostic and management challenges due to the lack of reliable biomarkers. In this study, we prospectively evaluated clinical data and treatment response which were correlated with different biomarkers. METHODS: The study was conducted at the University Hospital of Cologne. 20 patients with EPTB were enrolled. We analyzed plasma interferon-γ-inducible protein 10 (IP-10) levels in plasma by ELISA for up to 12 months of treatment. In addition, the QuantiFERON®-TB Gold Plus (QFT® Plus) test was performed during the course of treatment. Clinical data were assessed prospectively and correlated with QFT® Plus and IP-10 levels. RESULTS: Plasma IP-10 levels were found to be significantly increased (p < 0.001) in patients with extensive disease compared to patients with limited disease (cervical lymph node TB) or healthy controls. In patients with clinically confirmed paradoxical reaction (PR), a further increase of IP-10 was noted. IFN-γ measured by the QFT® Plus test did not decrease significantly during the course of treatment. Of note, in four EPTB patients (20%) without radiographic pulmonary involvement, sputum culture was positive for Mycobacterium tuberculosis. CONCLUSION: Our data demonstrate that IP-10 may be a valuable biomarker for estimation of disease severity in EPTB and monitoring of the disease course in extensive forms. However, IP-10 may be less suitable for diagnosis and monitoring of EPTB patients with limited disease. The QFT® Plus test does not appear to be a suitable marker for therapy monitoring. Sputum should be examined in EPTB patients even in case of normal diagnostic imaging of the chest.

Prevalence of positive IGRAs and innate immune system in HIV-infected individuals in Japan.

INTRODUCTION: Human immunodeficiency virus (HIV) infected individuals are at increased risk of developing active tuberculosis (TB). TB incidence remains higher than in non-HIV subjects after antiretroviral therapy (ART) initiation. This study was conducted to estimate the prevalence of positive IGRA, reflecting latent tuberculosis infection and/or a history of active TB, in HIV-infected individuals after ART initiation in Japan. METHODS: Two IGRAs (Interferon (IFN)-γ release assays), QuantiFERON®-TB Gold Plus (QFT-Plus) and T-Spot®.TB (TSPOT), were used. We also analyzed the TB associated risk factors for the IGRAs results and the role of CD4+ T-cells, CD8+ T-cells and NK cells for producing IFN-γ. We also analyzed the risk factors for positive IGRA responses and the role of CD4+ T-cells, CD8+ T-cells and NK cells for producing IFN-γ. RESULTS: One hundred eight-four subjects were prospectively enrolled. Median age was 49 years. The positivity rates of QFT-Plus and TSPOT were 7.6% [95%CI 4.6-12.4] and 2.7% [95%CI 1.2-6.2], respectively, with significant difference. TB-associated risk factors and NK cells ≥300/µL were selected as independently significant factors by multivariate logistic regression. The NK cell count revealed significant linear regression with IFN-γ production responding to TB-specific antigens. CONCLUSIONS: The prevalence of positive IGRAs was 2.7%-7.6%. QFT-Plus would be practical for a higher positivity rate and reflect TB risk factors. The innate immune system, referring to IFN-γ production, plays an important role in the immune response to TB-specific antigens even after initiating ART.

Comparison of QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-Tube tests for patients with active and latent tuberculosis: A prospective cohort study.

INTRODUCTION: We aimed to determine the diagnostic performance and clinical value of the QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold Plus (QFT-Plus) tests in patients with active tuberculosis (TB) or latent TB infection (LTBI). METHODS: We prospectively enrolled 140 patients, including 63 with active TB and 77 with LTBI, between March 2017 and October 2018. QFT-GIT and QFT-Plus were performed simultaneously in all subjects. RESULTS: QFT-Plus and QFT-GIT test results showed significant agreement, in both active TB and LTBI patients, in terms of the interferon-γ concentration and interpretation result. QFT-Plus had higher sensitivity than QFT-GIT for predicting active TB (82.5% vs. 77.8%) and showed fewer false-negative and indeterminate results in both active TB and LTBI patients due to its "TB2 tube". The QFT-Plus TB2-TB1 value was higher in the active TB group than in the LTBI group. The QFT-Plus TB1-Nil and TB2-Nil values were useful in predicting remote LTBI, rather than recent LTBI. CONCLUSIONS: QFT-Plus showed good agreement with QFT-GIT in both active TB and LTBI patients, and higher sensitivity for predicting active TB than QFT-GIT. The QFT-Plus TB2 tube results, which reflect CD8+ T cell immunity, may improve predictive accuracy and detection of the immune response associated with active TB and LTBI.

Clinical evaluation of QuantiFERON®-TB Gold Plus directly compared with QuantiFERON®-TB Gold In-Tube and T-Spot®.TB for active pulmonary tuberculosis in the elderly.

BACKGROUND: Reduced sensitivity of tuberculosis (TB) interferon-γ release assays (IGRAs) among the elderly has been reported, which is presumably due to diminished immune function. We evaluated the clinical performance of QuantiFERON®-TB Gold plus (QFT-Plus) compared with QuantiFERON®-TB Gold In-Tube (QFT-GIT) and T-Spot®.TB (T-SPOT) in the elderly. METHODS: Blood samples for all three IGRAs were drawn at the same time from all the participants. Both CD4 and CD8 T-cell counts in patients' peripheral blood were also measured. RESULTS: A total of 142 active pulmonary TB patients (median age: 84, interquartile range; 76-89 years) were recruited. The sensitivities of the tested IGRAs (excluding invalid/indeterminate cases) were as follows: QFT-Plus, 93.6%; QFT-GIT, 91.4%; and T-SPOT 68.1%. QFT-Plus displayed significantly higher sensitivity than T-SPOT (p < 0.00001). All three IGRAs exhibited the same specificity (100%), as assessed using blood samples from healthy, low TB-risk individuals (n = 118; median age: 39, IQR; 32-47 years). Positivity in 43 active TB patients with CD4 T-cell counts <200/µL, 39 of whom were ≥80 years of age, was as follows: QFT-Plus, 83.7%; QFT-GIT, 74.4%; and T-SPOT, 58.1%. The difference between TB2-TB1 of the QFT-Plus assay was statistically correlated with CD8 but not CD4 T-cell counts in blood (r = 0.193, p = 0.0298). CONCLUSIONS: QFT-Plus showed high performance in the detection of TB infection in patients irrespective of their advanced age (≥80 years) or lower CD4 counts. QFT-Plus can be useful for the diagnosis of TB infection in all patients, including those who are elderly and/or immunocompromised.

Fourth-Generation QuantiFERON-TB Gold Plus: What Is the Evidence?

QuantiFERON-TB Gold Plus (QFT-Plus) is the latest generation of interferon gamma release assays (IGRAs) to receive approval from the U.S. FDA, replacing its predecessor, QuantiFERON-TB Gold In-Tube (QFT-GIT). The novelty of QFT-Plus is that it elicits a response from CD8 T cells, in addition to CD4 T cells, thus collecting a broader response from T-cell subsets than QFT-GIT. It was developed with the aim to improve the detection of latent tuberculosis infection (LTBI), especially among recently exposed contacts, immunocompromised hosts, and young children. In this minireview, we summarize the performance of QFT-Plus compared with that of QFT-GIT among active tuberculosis (TB) patients (a surrogate for LTBI patients), high-risk populations, and low-risk individuals based on recent publications. Studies comparing QFT-Plus to QFT-GIT currently do not support the superior performance of QFT-Plus in individuals with active TB and LTBI. The difference in sensitivity between QFT-Plus and QFT-GIT in active TB patients was not significant in nearly all studies and ranged from -4.0 to 2.0%. Among high-risk groups, the agreement between QFT-Plus and QFT-GIT was 89.9 to 96.0% (kappa coefficient range, 0.80 to 0.91). The specificity in the low-risk population was slightly lower for QFT-Plus than for QFT-GIT, with the difference ranging from -7.4 to 0%. Further studies are needed to accurately evaluate the sensitivity of QFT-Plus in immunocompromised hosts and children. In addition, further evidence is required to validate a modified interpretation of QFT-Plus for the identification of false-positive results in low-risk health care workers.

QuantiFERON-TB Gold Plus with Chemiluminescence Immunoassay: Do We Need a Higher Cutoff?

QuantiFERON-TB Gold Plus (QFT-Plus) is the most widely used interferon gamma release assay (IGRA) for the diagnosis of latent tuberculosis infection (LTBI). The aim of this study was to compare QFT-Plus results by enzyme-linked immunosorbent assay (ELISA) on the SkyLab system with those obtained with chemiluminescence immunoassay (CLIA) on the Liaison XL analyzer. Agreement between the two assays was evaluated on 419 QFT-Plus blood samples and was found to be substantial (75.4%); higher agreement was found for positive (95.4%) and negative (80.4%) results, while most discordances were due to ELISA-indeterminate/CLIA-determinate results. According to Italian Clinical Microbiologist Association recommendations, in samples (n = 79) with a borderline result in ELISA (0.20 to 0.70 IU/ml), CLIA median values statistically increased (from 0.29 to 0.59 IU/ml for TB1 and from 0.32 to 0.60 IU/ml for TB2) but remained in the borderline range. Linear regression analysis indicated a substantial correlation between ELISA and CLIA for antigen tubes TB1 (Pearson's r = 0.8666) and TB2 (Pearson's r = 0.8728), but CLIA produced higher values than ELISA. Receiver operating characteristic (ROC) analysis showed that the optimal cutoff value in CLIA was 0.45 IU/ml for TB1 and 0.46 IU/ml for TB2. In conclusion, automated QFT-Plus with CLIA is comparable to QFT-Plus performed by ELISA. Within the linearity range of the test, CLIA detects higher quantitative values than ELISA, resulting in a higher number of determinate results and the conversion of samples that were close to the cutoff into positive borderline results. A higher cutoff for QFT-CLIA needs to be defined based on clinical diagnostic criteria.

The reliability of tuberculin skin test in the diagnosis of latent tuberculosis infection in psoriasis patients: A case-control study.

Tuberculin skin test (TST), which is used in the diagnosis of latent tuberculosis infection, may cause Koebner's phenomenon and false-positive results in psoriasis patients. The purpose of this study is to compare TST with QuantiFERON-TB Gold Plus (QFT-plus) test in psoriasis patients and to determine the effects of psoriasis on TST results. Ninety-two psoriasis patients and 30 control subjects were included in the study. QFT-plus test, TST, and prick test to distinguish the increase of induration because of the skin trauma were performed on both groups. The demographics, risk factors for latent tuberculosis infection, BCG vaccination history, Koebner's history, psoriasis severity, and treatment history of the patients were recorded. The effects of these variables on test results were investigated by comparing those with control group. The criteria of National Tuberculosis Diagnosis and Treatment Guidelines were used in the evaluation of test results, and threshold value of positivity for TST was taken as 10 mm in BCG-vaccinated patients who are planned to start biological treatment. Prick test results were negative in the control group. There was no significant relation between the results of prick test and TST induration diameters in the patient group. Although TST positivity was significantly higher in patients (62%) compared with control group (33%), QFT-plus test results were not statistically different between two groups. Agreement between two tests was determined to be low in patient group with 48% (K = 0.1), and it was determined to be moderate with 77% in control group (K = 0.4). QFT-plus test was found to be negative in 46 of 57 TST-positive patients (80.7%) in patient group. It was determined in both groups that vaccination did not have any effect on test results. When threshold value was lowered to 5 mm in patient group without considering BCG reaction, the number of TST-positive patients increased from 57 to 65. Mean TST induration diameter was 10 mm and 14 mm in cases with mild and moderate to severe clinical manifestation, respectively (P = .04). However, no effect of disease period and treatment was determined on both test results. TST positivity was higher in psoriasis patients compared with control group. It was considered due to the increased reaction of the skin to mycobacterial antigens rather than the Koebner's response. Although TST results were not affected by BCG, it was concluded that a 10-mm threshold value of positivity was a suitable approach in order to reduce the number of patients receiving unnecessary preventive treatment in patients who are considered to initiate biologic agents. Furthermore, it was also concluded that QFT-plus test may be preferred in psoriasis patients since it is applied in vitro and its specificity is higher and not affected by disease severity.

Effect of refrigeration of blood samples in lithium-heparin tubes on QuantiFERON TB Gold Plus test result.

The QuantiFERON TB Gold Plus (QFT-Plus) test is a newly approved interferon-gamma releasing assay test for detecting latent tuberculosis. Although blood samples for QFT test can be refrigerated for 48 h in lithium-heparin tubes according to package inserts, no published data are available on the effects of sample refrigeration on the test results. We conducted a clinical study that aimed to elucidate whether sample refrigeration for 48 h affects QFT-Plus test results. We collected 2 blood samples each from 40 participants for QFT-Plus; one sample was refrigerated before incubation for QFT-Plus assay, while the other sample was incubated soon after collection and treated as control. After comparing QFT-Plus test results of refrigerated samples and control samples, the concordance rate and kappa coefficient between them were 95% and 0.90, respectively. Thus, blood samples for QFT-Plus test can be refrigerated for 48 h in lithium-heparin tubes without influencing the test results.

Positivity rate of interferon-γ release assays for estimating the prevalence of latent tuberculosis infection in renal transplant recipients in Japan.

Renal transplant recipients are at increased risk of reactivating latent tuberculosis infection (LTBI) and developing active tuberculosis. QuantiFERON®-TB Gold Plus (QFT-Plus) has two TB-specific antigens tubes (TB1 and TB2). TB1 elicits CD4 T-cell response, and TB2 elicits both CD4 and CD8 T-cells responses, with expected increased sensitivity. The aim of this study was to estimate the prevalence of LTBI in renal transplant recipients in Japan. We conducted a cross-sectional study by using two interferon-γ release assays (IGRAs), QFT-Plus and T-SPOT®.TB (TSPOT). One hundred thirty-five recipients were prospectively enrolled. The median age was 49 years (range: 20 to 79). The positivity rates of QFT-Plus and TSPOT were 5.9% (95%CI 3.0-11.3) and 3.7% (95%CI 1.6-8.4), respectively, with no significant difference. The concordance rate was 95.5% (κ coefficient, 0.76). Age of 60 years and higher was related to the higher positivity rate in both QFT-Plus and TSPOT. The positivity rates of TB1 and TB2 were 5.1% (95%CI 2.5-10.2) and 5.9% (95%CI 3.0-11.2), respectively, with no significant difference. The concordance rate was 99.3% (κ coefficient, 0.93). TB2 did not show a higher positivity rate compared with TB1. The estimated prevalence of LTBI by using the both IGRAs was 3.7-5.9% in renal transplant recipients. These results were equivalent to the IGRAs positivity rate in the general Japanese population, even under the condition of immunosuppressive therapy. In consideration of the higher risk of developing active TB from LTBI, we can use both IGRAs as acceptable tools for LTBI diagnosis in renal transplant recipients.

Comparison of the QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-Tube Interferon Gamma Release Assays in Patients at Risk for Tuberculosis and in Health Care Workers.

The QuantiFERON-TB Gold Plus (QFT-Plus; Qiagen, Germantown, MD) interferon gamma release assay (IGRA) received FDA clearance in 2017 and will replace the prior version of the assay, the QFT-Gold In-Tube (QFT-GIT). Here, we compared performances of the QFT-Plus assay and the QFT-GIT version in a diverse patient population, including patients undergoing evaluation for or follow-up of latent tuberculosis infection (LTBI; n = 39) or active TB infection (n = 3), and in health care workers (HCWs; n = 119) at Mayo Clinic (Rochester, MN). Compared to the QFT-GIT, the QFT-Plus assay showed 91.2% (31/34) positive, 98.4% (124/126) negative, and 96.6% (156/161) overall qualitative agreement among the 161 enrolled subjects, with a Cohen's kappa value of 0.91 (excellent interrater agreement). Among the 28 patients diagnosed with LTBI at the time of enrollment, the QFT-GIT and QFT-Plus assays agreed in 24 (85.7%) patients; in all four discordant patients, the positivity of the QFT-GIT or QFT-Plus IGRA was associated with low-level interferon gamma (IFN-γ) reactivity, ranging from 0.36 IU/ml to 0.66 IU/ml. Additionally, we document a high degree of correlation between IFN-γ levels in the QFT-GIT TB antigen tube and each of the two QFT-Plus TB antigen tubes, as well as between the QFT-Plus TB1 and TB2 tubes (Pearson's correlation coefficients [R] > 0.95). Overall, we show comparable results between the QFT-GIT and QFT-Plus assays in our study population composed of subjects presenting with a diverse spectrum of TB infections. Our findings suggest that the necessary transition to the QFT-Plus assay will be associated with a minimal difference in assay performance characteristics.

QuantiFERON-TB Gold Plus Is a More Sensitive Screening Tool than QuantiFERON-TB Gold In-Tube for Latent Tuberculosis Infection among Older Adults in Long-Term Care Facilities.

We investigated the prevalence of latent tuberculosis infection (LTBI) among the residents in seven long-term care facilities (LTCFs) located in different regions of Taiwan and compared the performance of two interferon gamma release assays, i.e., QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold Plus (QFT-Plus) for screening LTBI. We also assessed the diagnostic performance against a composite reference standard (subjects with persistent-positive, transient-positive, and negative results from QFTs during reproducibility analysis were classified as definite, possible, and not LTBI, respectively). Two hundred forty-four residents were enrolled, and 229 subjects were included in the analysis. The median age was 80 years (range, 60 to 102 years old), and 117 (51.1%) were male. Among them, 66 (28.8%) and 74 (32.3%) subjects had positive results from QFT-GIT and QFT-Plus, respectively, and the results for 215 (93.9%) subjects showed agreement. Using the composite reference standard, 66 (28.8%), 11 (4.8%), and 152 (66.4%) were classified as definite, possible, and not LTBI, respectively. For definite LTBI, the sensitivity, specificity, positive predictive value, and negative predictive value of QFT-GIT were 89.4%, 95.7%, 89.4%, and 95.7%, respectively, and those for QFT-Plus were 100.0%, 95.1%, 89.2%, and 100.0%, respectively. The sensitivity of QFT-GIT decreased gradually with patient age. Compared to QFT-GIT, QFT-Plus displayed significantly higher sensitivity (100.0% versus 89.4%, P = 0.013) and similar specificity (95.1% versus 95.7%). In conclusion, a high prevalence of LTBI was found among elders in LTCFs in Taiwan. The new QFT-Plus test demonstrated a higher sensitivity than QFT-GIT in the older adults in LTCFs.

Lymphocyte subset analysis in QuantiFERON-TB Gold Plus and T-Spot.TB for latent tuberculosis infection in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an immune mediated inflammatory disorder, and immune suppressive drugs are prescribed. RA patients receiving treatments are in a kind of immunosuppressive condition that presents increased risk of developing active tuberculosis. Accurate diagnosis of latent tuberculosis infection (LTBI) is recommended for RA. QuantiFERON®-TB Gold Plus (QFT-Plus), a novel IGRA, has two tubes (TB1 and TB2). TB2 is designed to elicit both CD4 and CD8 T-cell responses, with expected increased sensitivity. We conducted a cross-sectional study to compare two IGRAs, QFT-Plus and T-SPOT®.TB (TSPOT), in RA. One hundred fifty-two RA patients (median age: 66.5 yrs) were enrolled. QFT-Plus and TSPOT were concurrently conducted. Lymphocyte subsets (CD4 T-cell and CD8 T-cell) were also measured. The positivity rates of QFT-Plus and TSPOT were 9.7% and 4.5%, respectively, with the difference being significant (P < 0.01). The positivity rates in TB1 and TB2 were 9.1% and 7.1%, respectively; the difference was not significant (P = 0.18). Patients with CD4 T-cell ≥650/µL and CD8 T-cell ≥400/µL had significantly higher positivity rates in both QFT-Plus and TSPOT in comparison with other groups (P < 0.01 and P < 0.05, respectively). QFT-plus demonstrated a higher positivity rate than TSPOT. However, there was little additional effect for detecting LTBI by TB2. Lymphocyte subsets were strongly associated with immune response in both QFT-Plus and TSPOT. LTBI should not be ruled out even with a negative IGRA result in patients with CD4 T-cell <650/µL or CD8 T-cell <400/µL.