3. 11 0 obj <> endobj This is because everyone's immune systems are different. NB: QFT, QuantiFERON-TB Gold; ICU, intensive care unit; IFN-, interferon . In the context of culture-confirmed TB, QFT testing has been associated with negative sensitivity (70%) (26, 27). The mitogen tube must have a gamma interferon value 0.5 IU/mL higher than the value of the Nil tube, for the positive control and the test to be valid. Extremes of age are associated with indeterminate QuantiFERON-TB gold assay results. 0000002253 00000 n Baseline characteristics of patients according to the mitogen response on QFT testing. It's not recommended for children who are under five years old (under two years old for immigration requirements). Also referred to as TB disease, this type of tuberculosis is contagious. QuantiFERON; infection; mitogen; mortality; outcomes. 0000010668 00000 n The Mitogen minus Nil value serves as the positive control, demonstrating the successful responsiveness of the T lymphocytes in patient specimen. All values are IU/ml IFN-. Performance. Clin Chim Acta 2014;430:79-83. QFT4. (2017) 49:1602102. doi: 10.1183/13993003.02102-2016. M. tuberculosis complex infection unlikely. More automation will be needed to accurately measure the QFT response. Powell RD 3rd, Whitworth WC, Bernardo J, Moonan PK, Mazurek GH. quantiferon mitogen minus nil normal range. False Discovery Rate post hoc correction for multiple comparisons was used and P value reported in the figure : *P < 0.05; **P < 0.01. The test is based on the quantification of interferon-gamma (IFN-) released from sensitized lymphocytes in whole blood incubated overnight with purified protein derivative (PPD) from M. tuberculosis and control antigens. The package insert also advises that the kit provides three collection tubes which have had antigens dried onto their walls and that these tubes must be transferred to an incubator within 16 hours of blood collection. Results: A total of 872 patients were included. Decreasing mitogen response (normal, weak and negative, respectively) was associated with increasing length of hospital stay [median (interquartile range) 5 (313), 11 (521) and 15 (1030) days; p < 0.001] and increasing hospital mortality (3, 7, and 15%; p < 0.001). LabReqs. QuantiFERON TB1 Ag Value 0.02 IU/mL 01 QuantiFERON TB2 Ag Value 0.02 IU/mL 01 QuantiFERON Nil Value 0.02 IU/mL 01 QuantiFERON Mitogen Value 0.10 IU/mL 01 QuantiFERON-TB Gold Plus NOTE [A] 01 NOTE: Indeterminate NOT Intermediate Reference Range: Negative 20 . You must tell your doctor what medicine you are taking, your medical history and if you are pregnant or breastfeeding. I was so amazed with their customer service. doi: 10.1186/cc10112, 12. (2010) 35:1179-82. . cuban cookbook nitza villapol. There are two types of tuberculosis latent TB and active TB. A p-value < 0.05 was considered statistically significant. To better evaluate the IFN responses to mitogen stimulation, we performed the analysis using the values without transforming the IFN values > 10 IU/mL in values = 10 (B) and the values converted in 10 IU/mL (C). The analysis for the first and second measurements across the full range of nil, mitogen, and TB responses showed mean differences of 0.1 IU/ml, 0.2 IU/ml, and 0.1 IU/ml, respectively. In the United States, the test is widely available from state public health laboratories, hospitals, and commercial laboratories. reduced by the IFN- concentration in nil tube. Ashlee Arnold. A high altitude kit is also available for . QFT results indicative of M. tuberculosis infection include the following three criteria: (mitogen -- nil) and (tuberculin -- nil) are both >1.5 IU; and 0000015986 00000 n official website and that any information you provide is encrypted quantiferon mitogen value normal range Learn how we helped our several clients grow in online business.It will give you an idea of our capabilities. QFT was less frequently positive if mitogen response was weak (25% of cases) compared to normal (80% of cases). The negative and weak mitogen response groups were younger (p < 0.001 for both) than normal response group and less frequently immunocompromised (p < 0.001 for both). Hradsky O, Ohem J, Zarubova K, Mitrova K, Durilova M, Kotalova R, et al. Septic shock as sepsis with persisting hypotension requiring vasopressors to maintain mean arterial pressure 65 mm Hg and had a serum lactate level >2 mmol/L (18 mg/dL) despite adequate volume resuscitation (19). Finally, in hospitalized patients who underwent a QFT, we observed that weaker IFN- production was associated with a worse prognosis, considering infectious complications, ICU admission, in-hospital mortality, and hospital length of stay. For QFT-G, the antigens include mixtures of synthetic peptides representing two M. tuberculosis proteins, ESAT-6 and CFP-10. Multivariable analyses identified age, immunodepression, serum albumin, hemoglobin, and neutrophil and lymphocyte counts as factors associated with a negative mitogen response, as previously reported (3, 7). Hirsch CS, Toossi Z, Othieno C, Johnson JL, Schwander SK, Robertson S, et al. 13 0 obj<>stream (2020) 11:1364. doi: 10.3389/fimmu.2020.01364. Tuberculosis, or TB, is a highly contagious and infectious airborne disease that affects the respiratory system, particularly the lungs. Retrospective, case-control study in hospitalized patients who underwent QFT testing in two hospitals between 2016 and 2019. IGRAs cannot distinguish between latent infection and active tuberculosis (TB) disease, and should not be used as a sole method for diagnosis of active TB, which is a microbiological diagnosis. Unauthorized use of these marks is strictly prohibited. Eur Respir J. There is limited information on its suitability for those who are immunocompromised. (2014) 52:2694-7. doi: 10.1128/JCM.00814-14, 9. Blood samples must be processed within 16 hours after collection while white blood cells are still viable. QuantiFERON Mitogen Value test cost is between $149.00 and $535.99. The QFT-G results are based on the amount of IFN-gamma that is released in response to the antigens. Infections are frequent in hospitalized patients, but our results suggest QFT should not be performed until after recovery. Acute infections observed at the time of QFT sampling were mainly bacterial (85%) and of pulmonary origin (56%) (Supplementary Table 1). %PDF-1.5 % Immunocompromised status can result in indeterminate QuantiFERON-TB Gold In-Tube (QFT-GIT) results, but the association of indeterminate results with immunocompetent status in children is unknown. The negative correlation we observed between C-reactive protein and mitogen response further supports this assumption. (2021) 2021:40214. We then addressed the problem of the cut-offs for mitogen positivity. Proportion of patients with infectious complications during hospital stay after QFT sampling (A), intensive care unit (ICU) admissions (B), in-hospital mortality (C) and the median (interquartile range) hospital length of stay (D) were recorded and represented according to the mitogen response: negative (IFN- 0.5 IU/ml), weak (IFN- = 0.52 IU/ml) and normal (IFN- > 2 IU/ml). Comparison of two commercial interferon-gamma assays for diagnosing Mycobacterium tuberculosis infection. Epub 2011 Jun 8. 0000024723 00000 n We can assume that confirmed TB cases with extensive diseases and/or those with systemic involvement were associated with both systemic inflammation and T-cell exhaustion. doi: 10.1371/journal.pone.0020061. Specimen Requirements: . Copyright 2022 Jacquier, Binquet, Manoha, Audia, Simonet-Lamm, Casenaz, Sow, Piroth and Blot. QFT4. LOINC. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements. NV CB and MB: supervision. One milliliter of whole blood was incubated for 1624 h at 37C, after which plasma was harvested and tested using an enzyme-linked immunosorbent assay for the presence of IFN- produced in response to the peptide antigens or PHA (mitogen). Value. Boomer JS, Shuherk-Shaffer J, Hotchkiss RS, Green JM. Clin Microbiol Rev. Unusual interferon gamma measurements with QuantiFERON-TB Gold and QuantiFERON-TB Gold In-Tube tests. Unlike a TB skin test, which needs two visits, you dont have to go back to the testing facility for your test results. The secondary objectives were to study differences between patients with a weak or a negative mitogen response, the association between mitogen response and clinical outcomes, and the QFT results in TB patients according to mitogen response. Its an Interferon Gamma Release Assay (IGRA) test that involves taking a blood sample which will then be analyzed in a lab. Controls were defined as patients with a normal mitogen response IFN- > 2 IU/ml. The reporting range for the Tb Antigen-Nil and Mitogen-Nil is 0 - >10 IU/mL.) Z*t8GBg3SFvJnA05%a Eur Respir J. Test Result Name. The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmed.2022.876864/full#supplementary-material. The test result value may optionally contain a relational operator from the set {=, , >, >=}. It decreased again in the U.S. in 1993 but is still a concern as tuberculosis cases can re-emerge. 0000002219 00000 n Does not boost responses measured by subsequent tests, which can happen with tuberculin skin tests (TST). xref In case of both immunodepression and diabetes, the effect of these both variables was lowered (p for interaction = 0.011 when comparing negative vs. normal mitogen response groups). Study protocol and data collection were registered with the CNIL (Commission nationale de linformatique et des liberts) and are in accordance with French (Loi Informatique et Libert n7817 du 6 janvier 1978) and European (GRPD EU 2016/679) regulations on data protection and patient information (Commitment of compliance MR004 n2210228 of 3 December 2018) with a waiver of informed consent given the non-interventional study design. Huang et al. Mitogen Control, TB Antigen) Minimum Volume: 1.0 ml required per tube; Fill tubes to the black line on the side of the tube label = 1.0 ml. 20. Among tuberculosis patients, a weak mitogen response was associated with a false-negative QFT result (75%) compared to a normal response (20%). 10.1183/13993003.01267-2017 0000034863 00000 n Nil 8.0 and TB1 and TB2 <0.35 or 0.35 and <25% of Nil and Mitogen minus Nil <0.5 QFT-Plus Indeterminate 4 Detect TB infection with confidence 07/2017. For instance, the reported frequency of indeterminate results is higher in septic patients [up to 29% (5)] than in healthy individuals [1.5% (9)]. An individual is considered positive for M. tuberculosis infection if the IFN-gamma response to TB antigens is above the test cut-off (after subtracting the background IFN-gamma response in the negative control). The QFT assay consists of four tubes: the negative-control (nil) tube that measures background IFN, a positive control (mitogen) tube with a non-specific stimulant and two antigen tubes (TB1 and TB2) for diagnosis of latent M. tuberculosis infection. Name Value Reference Range NIL 0.040 UI/mL MITOGEN-NIL 10.065 IU/mL TB Ag-NIL 0.479 IU/mL INTERFERON GAMMA RESULTS POSITIVE NEGATIVE. Normal range/expected value(s) for a specific disease state. Active TB, on the other hand, is when you are infected with the bacteria and show symptoms of the illness. In addition, the contribution of the two tubes TB1 and TB2, evaluating, respectively, the T-CD4 and T-CD8 responses, did not allow to mitigate this limitation since both T-CD4 and CD8 are non-selectively affected by T-cell exhaustion during sepsis (23). MJ, MB, and CB: drafting of the manuscript. [4][5] However, one of the five sites involved in the CDC study reported less agreement. This positive result was associated with an improved mitogen response (mitogen [IFN-] > 10 IU/mL), decreased C-reactive protein levels, and no change in the lymphocyte count (Supplementary Figure 4). May also include abnormal ranges. A recently published study[7] demonstrated that a positive IGRA result is predictive of future active TB risk. ^><4RNC;w@.J./[^=z/MLKH%E8o|tS[,nK.?n^Z7jXc O&ZG?>E[=//#BVb]hz=v.sYiyy]]~[[,S*?}w6X,9gJKq#t%@WsoW{SOt$kq=D[`/F3~hQxI N9Jqh6T,$Q~(,P:EAX 24B IbB`BjbgC So they gave me water and made sure I was okay to leave. Interpretation of QFT results is stratified by estimated risk for infection with M. tuberculosis, in a manner similar to that used for interpreting TST with different cut-off values. The nil tube value is subtracted from the values of the mitogen, TB1, and TB2 tubes for the final result of the respective tubes. Clinical outcomes (onset of an acute infection, sepsis or septic shock after QFT sampling, ICU admission, in-hospital mortality and hospital length of stay) were also recorded. (2009) 33:812-5. doi: 10.1183/09031936.00075008, 8. For variables whose association with mitogen response was non-loglinear, the predicted probabilities of negative or weak response were estimated and plotted against the values of the variables, along with the CIs. Errors in collecting or transporting blood specimens or in running and interpreting the assay can decrease the accuracy of QFT-G. In this case, generally, the test must be retaken with a fresh blood sample. The interferon gamma (IFN-) response to phytohemagglutinin (PHA) as a mitogen is used as a positive control to confirm the proliferative capacity of patient lymphocytes at the time of sampling (2). 4. Table 2 . <<022157bd818f5e479a168ae0d41e7b05>]>> Bethesda, MD 20894, Web Policies The presence of an active infection within the last 3 months or at the time of the QFT sampling were recorded if the infection was clinically/biologically suspected or confirmed by the clinician in charge of the patient. (2019) 158:49-54. doi: 10.1016/j.rmed.2019.10.004, Keywords: QuantiFERON, mitogen, infection, outcomes, mortality, Citation: Jacquier M, Binquet C, Manoha C, Audia S, Simonet-Lamm A-L, Casenaz A, Sow A-K, Piroth L and Blot M (2022) Beyond QuantiFERON-TB Results, the Added Value of a Weak Mitogen Response. Components Reference Interval; QuantiFERON-TB1 minus NIL: 0.34 IU/mL or less: QuantiFERON-TB2 minus NIL: 0.34 IU/mL or . This well-known T-cell exhaustion phenotype (including quantitative and qualitative lymphocyte defects) is associated with worse outcomes during sepsis (14). 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C, Johnson JL, Schwander SK, Robertson S, et al tests ( TST.. 0.040 UI/mL Mitogen-Nil 10.065 IU/mL TB Ag-NIL 0.479 IU/mL interferon gamma results POSITIVE negative commercial interferon-gamma assays for diagnosing tuberculosis... And mitogen response on QFT testing in two hospitals between 2016 and 2019 further supports this.! That a POSITIVE IGRA result is predictive of future active TB old immigration! And CFP-10 disease, this type of tuberculosis is contagious from state public health laboratories, hospitals and...