QuantiFERON-TB In-Tube Research Articles

Abstract 2526: Exploratory study of predicting systemic therapy response by IGRA in advanced stage NSCLC patients

Abstract Purpose: In this study, we aim to prospectively evaluate how patients’ pretreatment PSIG correlated with chemotherapy, immune checkpoint inhibitors (ICI) and epidermal growth factor receptor (EGFR) Tyrosine Kinasae Inhibior (TKI). Also, to assess the change of PSIG during anti-cancer treatment and the relation with clinical condition. Materials and Methods: Newly diagnosed advanced stage non-small cell lung cancer patients were enrolled. The inclusion criteria included pathology or cytology-proved stage IV and non-operable stage III non-small cell lung cancer, treatment-naïve, and planned to receive chemotherapy, EGFR-TKI therapy. Or, planned to receive any line of singe agent immunotherapy. We planned to enroll 30 patients in each treatment group (chemotherapy, immunotherapy, EGFR TKI therapy) with and additional control group of stage I NSCLC.Blood sample from each enrolled patient was obtained for INF-γ release assay (IGRA) within 3 days before the initiation of systemic therapy and 8-12 weeks after treatment. The IGRA was performed with QuantiFERON-TB In-Tube (QFT-GIT; Qiagen, Germany) according to the manufacture’s instruction. The amount of INF-γ produced in response to PHA is determined by the INF-γ level in the PHA-coated tube minus saline-coated tube, and is termed PHA-stimulated INF-γ (PSIG) level. Patients with PSIG level above 7.06IU were defined had high PSIG level according to our previous study. we also performed our in house INF-γ level by ELISA. Tumor response was assessed mainly by chest CT and brain MRI (if available) according to Response Evaluation Criteria in Solid Tumors (RECST). Results: Total 116 patients were enrolled. Demographic distribution was summarized in Table 1. Thirty-five of 116 (30.2%) patients had latent TB infection, while 12 patients (10.3%) had indeterminate OFT test, all due to low mitogen-stimulated INF-γ level. 84 patients had been obtained post-treatment blood test, and the box-plot of in-house INF-γ level were shown in Figure1. For stage I control group, INF-γ level seemed higher after surgery; for chemotherapy and immunotherapy, the INF-γ level also seemed increase among responders (who achieved disease control after treatment). There were no statistically difference of disease control rate between patients with high PSIG level and low PSIG level. Overall survival also showed no statistically difference between 2 PSIV level patient group among advanced stage NSCLC patients. Conclusions:There were no statistically different of disease control rate in PSIG high and low group. The increased trend of INF-γ level after surgery, immunotherapy and chemotherapy may suggested improving immune function after treatment even in the very early disease stage. Citation Format: Hsu Ching Huang, Chi-Lu Chiang, Yung-Hung Luo, Yuh-Min Chen, Chao-Hua Chiu. Exploratory study of predicting systemic therapy response by IGRA in advanced stage NSCLC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2526.

Latent tuberculosis infection prevalence in second generation immigrants from high to low TB burden countries

BackgroundLatent tuberculosis infection (LTBI) diagnosis in a country with a low tuberculosis burden is complicated. Since the prevalence of LTBI in second generation immigrants has not been well recognized, we conducted a cross-sectional study which aimed to explore the differences in LTBI prevalence between offspring of immigrants from high tuberculosis (TB) burden countries and those whose parents were born in countries with a low TB burden. MethodsBetween May 2014 and April 2018 young native Israelis who were required to perform pre-occupational tuberculin skin tests (TST) (medical and paramedical personnel or teaching assistants of immigrants from high TB burden countries) and who had a TST result of 10mm and above were tested for QuantiFERON-TB In Tube (QFT-GIT). Statistical comparisons were made between second generation immigrants and those with both parents from a low TB burden country. ResultsOf 102 patients, 71 were born to parents both of whom were from low-risk countries, 14 to one parent from a high-risk country and 17 to parents both of whom were from a high-risk country. The odds ratio for LTBI was 4.5 (95% CI, 1.2...17.2; p=0.03) if both parents were born in a high-risk country compared to both parents being from a low-risk country and 4.01 (95% CI, 1.12...14.3; p=0.03) higher compared to persons for whom at least one parent was born in a low-risk country. ConclusionThe risk for latent TB is significantly higher in second generation immigrants if both parents were born in a high-risk country. IGRA should be considered before treatment to patients with a positive TST if at least one parent was born in a low-risk country in order to confirm LTBI.

Dynamics of immune parameters during the treatment of active tuberculosis showing negative interferon gamma response at the time of diagnosis.

In the performance of interferon gamma release assays (IGRA) for the diagnosis of tuberculosis (TB) infection, false-negative results are a major obstacle. In active TB patients, treatment-dependent changes of the negative test results remain unknown. The treatment course of 19 smear-positive/culture-confirmed TB patients who had IGRA-negative results by QuantiFERON-TB in-tube (QFT-IT) method at the time of diagnosis (month 0) in a previous study, were monitored in the present study. Blood was further collected at months 2 and 7, and the concentrations of 27 immune molecules were measured in the plasma supernatants remaining after performing the IGRA, using a suspension array system. After initiating treatment, eight of the 19 QFT-IT-negative patients showed positive conversion, whereas the remaining 11 (58%) did not; the interferon gamma (IFN-γ) response was restored to levels higher than 1 IU/ml in only three of the eight patients with positive conversion. Plasma concentrations of interleukin 1 receptor antagonist, interleukin 2, and interferon gamma-induced protein 10 remained low after Mycobacterium tuberculosis-specific antigen stimulation at months 2 and 7 in the continuously QFT-IT-negative group, whereas the parameters were elevated only in the transiently QFT-IT-negative group. It was demonstrated that a majority of active TB patients showing negative IGRA results did not regain sufficient levels of immune responsiveness despite successful treatment.

A prospective longitudinal study evaluating the usefulness of the interferon-gamma releasing assay for predicting active tuberculosis in allogeneic hematopoietic stem cell transplant recipients

There is little information on the efficacy of interferon-gamma-releasing assays for predicting subsequent active tuberculosis in hematopoietic stem cell transplant (HCT) recipients. We prospectively enrolled adult patients admitted for allogeneic HCT during a 3-year period in an intermediate-tuberculosis-burden country. All the patients underwent QuantiFERON-TB In-Tube (QFT-TB) assay, while those enrolled during the first 2-year period also received the tuberculin skin test (TST). We observed the development of tuberculosis after HCT for additional 6-month. Of the 391 patients, 8 developed tuberculosis. Three of the 45 patients with positive QFT-TB results developed tuberculosis, while 5 of the 346 patients with negative or indeterminate QFT-TB outcomes developed tuberculosis (rate difference 2.7 per 100 person-years, P = 0.05). Of the 169 patients who underwent both TST and QFT-TB, 5 developed tuberculosis after HCT. None of the 19 patients with positive TST developed tuberculosis. Among the 150 patients with negative TST, there were 20 with positive QFT-TB and, of these, 3 developed tuberculosis, while 2 of the 130 patients with negative or indeterminate QFT-TB assays developed tuberculosis (rate difference 6.5 per 100 person-years, P = 0.004). Positive QFT-TB assay results predict subsequent development of tuberculosis in HCT recipients in whom latent tuberculosis cannot be detected by TST (NCT01021124).

Interferon-γ release assay in people infected with immunodeficiency virus

The present study aimed to use QuantiFERON TB Gold in tube (Cellestis Limited, Carnegie, Victoria, Australia) as a tool for the screening for tubercular infection in HIV-positive patients. Seventy-three HIV-positive subjects were tested. For each individual, QuantiFERON TB in tube was performed. The immunoassay was negative in 53 subjects, positive in eight and indeterminate in 12. The data obtained indicate that factors such as the CD4 cell count and their percentage, as well as the stage of the disease, could affect the performance of the interferon-γ release assay in populations at risk such as HIV-positive subjects.

Performance of Commercial Blood Tests for the Diagnosis of Latent Tuberculosis Infection in Children and Adolescents

The accurate diagnosis of latent tuberculosis infection reduces the risk of progression to severe disseminated disease. However, in young children, a major limitation of the standard tuberculin skin test is that false-negative results cannot be detected. The new interferon-gamma release assays QuantiFERON-TB Gold (Cellestis Carnegie Victoria, Australia), QuantiFERON-TB In-Tube (Cellestis), and T-SPOT.TB (Oxford Immunotec, Abingdon, United Kingdom) show promise of greater accuracy, but they may also be affected by impaired cellular immunity, resulting in indeterminate results (ie, insufficient response in positive-control wells). To evaluate the impact of age on the performance of interferon-gamma release assays when used in a routine hospital setting among children tested for suspected active or latent TB infection. We retrospectively studied 496 children 0 to 19 years of age who had been tested with the tuberculin skin test and at least 1 interferon-gamma release assay: 181 with QuantiFERON-TB Gold and 315 with QuantiFERON-TB In-Tube. In 154 of the children, paired interferon-gamma release assay testing was available: 87 with QuantiFERON-TB Gold/T-SPOT.TB and 67 with QuantiFERON-TB In-Tube/T-SPOT.TB. Compared with T-SPOT.TB, the rates of indeterminate results were significantly higher for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube. QuantiFERON-TB Gold and QuantiFERON-TB In-Tube also gave indeterminate results more frequently in children <4 years of age than in those >/=4 years of age. Indeterminate results were associated with younger age for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube but not for T-SPOT.TB. Considering age as a binary variable (<4 and >/=4 years of age), a significantly higher concentration of phytohaemagglutinin-produced interferon-gamma was observed in older children with both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube. Different blood tests for the diagnosis of latent tuberculosis infection in children seem to perform differently, because both QuantiFERON-TB tests were more likely than T-SPOT.TB to give indeterminate results in children <4 years of age.

Utility of QuantiFERON-TB In-Tube Test for Differentiating Active Tuberculosis from Latent Tuberculosis Infection in an Intermediate Burden Country

Utility of QuantiFERON-TB In-Tube Test for Differentiating Active Tuberculosis from Latent Tuberculosis Infection in an Intermediate Burden Country

Latent Tuberculosis in HIV positive, diagnosed by the M. Tuberculosis Specific Interferon-γ test

BackgroundAlthough tuberculosis (TB) is a minor problem in Denmark, severe and complicated cases occur in HIV positive. Since the new M. tuberculosis specific test for latent TB, the QuantiFERON-TB In-Tube test (QFT-IT) became available the patients in our clinic have been screened for the presence of latent TB using the QFT-IT test. We here report the results from the first patients screened.MethodsOn a routine basis the QFT-IT test was performed and the results from 590 HIV positive individuals consecutively tested are presented here. CD4 cell count and TB risk-factors were recorded from patient files.Main findings27/590(4.6%) of the individuals were QFT-IT test positive, indicating the presence of latent TB infection. Among QFT-IT positive patients, 78% had risk factors such as long-term residency in a TB high endemic area (OR:5.7), known TB exposure (OR:4.9) or previous TB disease (OR:4.9). The prevalence of latent TB in these groups were 13%, 16% and 19% respectively. There was a strong correlation between low CD4 T-cell count and a low mitogen response (P < 0.001;Spearman) and more patients with low CD4 cell count had indeterminate results.ConclusionWe found an overall prevalence of latent TB infection of 4.6% among the HIV positive individuals and a much higher prevalence of latent infection among those with a history of exposure (16%) and long term residency in a high endemic country (13%). The QFT-IT test may indeed be a useful test for HIV positive individuals, but in severely immunocompromised, the test may be impaired by T-cell anergy.