scholarly journals Species-Specific Interferon-Gamma Release Assay for the Diagnosis of Mycobacterium abscessus Complex Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Mathis Steindor ◽  
Florian Stehling ◽  
Margarete Olivier ◽  
Jan Kehrmann ◽  
Margo Diricks ◽  
...  

Mycobacterium abscessus complex (MABC) infection has a devastating impact on the course of cystic fibrosis (CF) and non-CF lung disease. Diagnosis of MABC pulmonary disease is challenging, and current diagnostic approaches lack accuracy, especially in CF. In this study, we aimed to establish an MABC-specific interferon-γ release assay to detect host immune responses to MABC and improve diagnostics of MABC infection by the detection of antigen-specific T cells. Four species-specific proteins of MABC were overexpressed in an Escherichia coli expression system. Purified proteins were used to stimulate peripheral blood mononuclear cells of study subjects in an ELISpot assay. Interferon-γ response of 12 subjects with established diagnosis of MABC infection (10 CF and two non-CF) was compared with 35 controls (22 CF and 13 non-CF) distributed to three control groups, 17 CF subjects without NTM infection, nine subjects with NTM infection other than MABC, and nine subjects with tuberculosis. Cellular in vitro responses in the MABC group were stronger than in the control groups, especially toward the protein MAB_0405c (39 vs. 4 spots per 300,000 PBMC, p = 0.004; data represent mean values) in all patients and also in the subgroup of CF subjects (39 spots vs. 1 spot, p = 0.003). Receiver operating characteristic curve analysis indicated that spot numbers of at least 20 were highly predictive of MABC infection (all patients: area under curve 0.773, sensitivity 58%, and specificity 94%; CF patients: area under curve 0.818, sensitivity 60%, and specificity 100%). In conclusion, we identified MAB_0405c as a protein that may stimulate MABC-specific interferon-γ secretion and may add to the diagnosis of MABC infection in affected patients.

Infection ◽  
2008 ◽  
Vol 36 (6) ◽  
pp. 597-600 ◽  
Author(s):  
K. Kösters ◽  
R. Nau ◽  
A. Bossink ◽  
I. Greiffendorf ◽  
M. Jentsch ◽  
...  

2015 ◽  
Vol 75 (4) ◽  
Author(s):  
M. Bugiani ◽  
S. Bonora ◽  
A. Carosso ◽  
P. Piccioni ◽  
M. Cavallero ◽  
...  

Background and Aim. Monitoring the efficacy of antituberculosis therapy is crucial. The aim of this work is to investigate the effect of tuberculosis treatment on interferon- γ response using Quanti-FERON©-TB Gold in tube (QFT-GIT). Methods. A total of 216 new pulmonary tuberculosis (TB) cases were tested with QFT-GIT at the start of the treatment and, randomly, once or twice between 90 and 180 days afterwards. Data was analysed using the random effect regression model analysis. Results. 63.4% of patients were positive at the QFTGIT (>.35 UI cut-off). TB cases showed a significant loglinear increase in interferon-γ (IFN-γ) concentration, over time of treatment: IFN-γ concentration increased by 78% after 6 months of treatment in acid-fast bacilli positive (A) and culture negative cases in culture confirmed cases the increase was 43% if A+ and 20% in A-. Conclusions. Effective therapy seems to restore cellular responses to Mycobacterium tuberculosis antigens. The potential use of interferon gamma release assay (IGRA) in monitoring response to TB treatment is hampered by the presence of active mycobacterial replication at baseline and needs further evaluation.


Author(s):  
Olga Adriana Caliman-Sturdza ◽  
Doina Mihalache ◽  
Catalina Mihaela Luca

AbstractThe new immunodiagnostic tests based on the Mycobacterium tuberculosis specific antigen, early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10), showed promising results in the diagnosis of tuberculosis infection. However, there are only few studies in the published literature on performance tests in cerebrospinal fluid. We investigated whether a rapid diagnosis of tuberculous meningitis (TBM) could be established by interferon-γ blood and cerebrospinal fluid (CSF) tests in children.We used the QuantiFERON-TB Gold in Tube test (QFT-IT) on blood and the QuantiFERON-TB Gold test (QFT-G) on the CSF of 63 subjects with TBM (including 25 case of definite TBM and 38 cases of probable TBM) and 62 controls.The CSF analyses indicated possible TBM in 63.4% of cases. The sensitivity of the CSF culture for Mycobacterium tuberculosis was only 39.6%. The sensitivity of the tuberculin skin test (TST) was 49.2% and the specificity was 88.6%. The estimated sensitivities of the QFT-G for the CSF and QFT-IT for the blood in culture confirmed TBM cases (gold standard) were 84% and 80%, respectively. The estimated specificities were 98.2% for the CSF and 87.9% for the blood. This study showed that the sensitivity of QFT for the CSF could be higher than TST and culture and slightly higher in CSF than in blood. The specificity of QFT-G for the CSF was higher those of the TST, but the specificity of QFT-IT is lower.QFT-G of the CSF is a useful diagnostic marker of tuberculosis that may improve the management of TBM, but the test results must be correlated with clinical, radiological and characteristics of CSF. New researches are needed to investigate the performance of QFT-G in the CSF compared with ELISPOT and PCR


Author(s):  
Yuanyuan Zhou ◽  
Huan Xiong ◽  
Rong Chen ◽  
Lixia Wan ◽  
Ying Kong ◽  
...  

Tuberculosis (TB) is the leading infectious cause of mortality worldwide. However, the diagnosis of TB, especially extrapulmonary TB (EPTB) diagnosis from lesion tissues, remains a challenge. Nucleic acid aptamers are analogous to antibodies and have advantages of easier modification, high specificity, and affinity. Mannose-capped lipoarabinomannan (ManLAM) is a unique surface lipoglycan component or constantly released from mycobacterium tuberculosis (M.tb) cell wall, which makes it a perfect candidate biomarker for TB diagnosis. Our present study aims to establish M.tb ManLAM aptamer-based immunohistochemistry (IHC) method for TB diagnosis. We performed TB diagnosis using 263 formalin-fixed paraffin-embedded tissue samples including 213 TB samples (pulmonary TB (PTB) and EPTB), and 8 samples from latent TB infection (LTBI) high risk subjects, and 42 samples from other non-TB patients with ManLAM aptamer-based IHC and routine laboratory TB diagnostic methods parallelly. The sensitivity and specificity of the ManLAM aptamer-based IHC were 86.38% and 92.86%, with much higher sensitivity than those of mycobacterial culture (9.66%) and acid-fast staining (AFS) (43.01%) and comparability to Interferon-gamma Release Assay (IGRA) (84.38%) and GeneXpert (79.31%). High agreement between ManLAM based-IHC and IGRA or GeneXpert for TB diagnosis were observed. Furthermore, ManLAM aptamer-based IHC combination with other routine TB laboratory diagnostic methods significantly increased the sensitivity up to 88.64%–97.92%. As our knowledge, this is the first report about aptamer-based IHC for disease diagnosis. Thus, ManLAM aptamer-based IHC has potentials for TB diagnosis, including PTB, and EPTB, and assists the diagnosis of LTBI with high effectiveness, feasibility, and easy production.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Konstantin P. Lyashchenko ◽  
Rena Greenwald ◽  
Javan Esfandiari ◽  
Alexis Lecu ◽  
W. Ray Waters ◽  
...  

A case of pulmonary tuberculosis caused byMycobacterium tuberculosiswas diagnosed in a horse. Clinical evaluation performed prior to euthanasia did not suggest tuberculosis, but postmortem examination provided pathological and bacteriological evidence of mycobacteriosis. In the lungs, multiple tuberculoid granulomas communicating with the bronchiolar lumen, pleural effusion, and a granulomatous lymphadenitis involving mediastinal and tracheobronchial lymph nodes were found. Serologic response toM. tuberculosisantigens was detected in the infected horse, but not in the group of 42 potentially exposed animals (18 horses, 14 alpacas, 6 donkeys, and 4 dogs) which showed no signs of disease. Diagnosis of tuberculosis in live horses remains extremely difficult. Four of 20 animal handlers at the farm were positive for tuberculous infection upon follow-up testing by interferon-gamma release assay, indicating a possibility of interspecies transmission ofM. tuberculosis.


2019 ◽  
Vol 71 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Gloria H Hong ◽  
Ana M Ortega-Villa ◽  
Sally Hunsberger ◽  
Ploenchan Chetchotisakd ◽  
Siriluck Anunnatsiri ◽  
...  

Abstract Background The natural history of anti-interferon-γ (IFN-γ) autoantibody-associated immunodeficiency syndrome is not well understood. Methods Data of 74 patients with anti-IFN-γ autoantibodies at Srinagarind Hospital, Thailand, were collected annually (median follow-up duration, 7.5 years). Annual data for 19 patients and initial data for 4 patients with anti-IFN-γ autoantibodies at the US National Institutes of Health were collected (median follow-up duration, 4.5 years). Anti-IFN-γ autoantibody levels were measured in plasma samples. Results Ninety-one percent of US patients were of Southeast Asian descent; there was a stronger female predominance (91%) in US than Thai (64%) patients. Mycobacterium abscessus (34%) and Mycobacterium avium complex (83%) were the most common nontuberculous mycobacteria in Thailand and the United States, respectively. Skin infections were more common in Thailand (P = .001), whereas bone (P < .0001), lung (P = .002), and central nervous system (P = .03) infections were more common in the United States. Twenty-four percent of Thai patients died, most from infections. None of the 19 US patients with follow-up data died. Anti-IFN-γ autoantibody levels decreased over time in Thailand (P < .001) and the United States (P = .017), with either cyclophosphamide (P = .01) or rituximab therapy (P = .001). Conclusions Patients with anti-IFN-γ autoantibodies in Thailand and the United States had distinct demographic and clinical features. While titers generally decreased with time, anti-IFN-γ autoantibody disease had a chronic clinical course with persistent infections and death. Close long-term surveillance for new infections is recommended.


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