Interferon-gamma Release Assay Research Articles

1-Year Incidence of Tuberculosis Infection and Disease Among Household Contacts of Rifampin- and Multidrug-Resistant Tuberculosis.

Tuberculosis infection (TBI) and TB disease (TBD) incidence remains poorly described following household contact (HHC) rifampin-/multidrug-resistant TB exposure. We sought to characterize TBI and TBD incidence at 1 year in HHCs and to evaluate TB preventive treatment (TPT) use in high-risk groups. We previously conducted a cross-sectional study of HHCs with rifampin-/multidrug-resistant TB in 8 high-burden countries and reassessed TBI (interferon-gamma release assay, HHCs aged ≥5 years) and TBD (HHCs all ages) at 1 year. Incidence was estimated across age and risk groups (<5 years; ≥5 years, diagnosed with human immunodeficiency virus [HIV]; ≥5 years, not diagnosed with HIV/unknown, baseline TBI-positive) by logistic or log-binomial regression fitted using generalized estimating equations. Of 1016 HHCs, 850 (83.7%) from 247 households were assessed (median, 51.4 weeks). Among 242 HHCs, 52 tested interferon-gamma release assay-positive, yielding a 1-year 21.6% (95% confidence interval [CI], 16.7-27.4) TBI cumulative incidence. Sixteen of 742 HHCs developed confirmed (n = 5), probable (n = 3), or possible (n = 8) TBD, yielding a 2.3% (95% CI, 1.4-3.8) 1-year cumulative incidence (1.1%; 95% CI, .5-2.2 for confirmed/probable TBD). TBD relative risk was 11.5-fold (95% CI, 1.7-78.7), 10.4-fold (95% CI, 2.4-45.6), and 2.9-fold (95% CI, .5-17.8) higher in age <5 years, diagnosed with HIV, and baseline TBI high-risk groups, respectively, vs the not high-risk group (P = .0015). By 1 year, 4% (21 of 553) of high-risk HHCs had received TPT. TBI and TBD incidence continued through 1 year in rifampin-/multidrug-resistant TB HHCs. Low TPT coverage emphasizes the need for evidence-based prevention and scale-up, particularly among high-risk groups.

Sustained cell-mediated but not humoral responses in rituximab-treated rheumatic patients after vaccination against SARS-CoV-2.

B-cell depleting monoclonal antibodies are associated with increased COVID-19 severity and impaired immune response to vaccination. We aimed to assess the humoral and cell mediated (CMI) immune response after SARS-CoV-2 vaccination in rituximab (RTX)-treated rheumatic patients. Serum and whole blood samples were collected from RTX-treated rheumatic patients 3-6 months after last vaccination against SARS-CoV-2. Serum was tested by ELISA for quantitative detection of anti-spike SARS-CoV-2 IgG. Cell-mediated variant-specific SARS-CoV-2 immunity (CMI) was assessed by interferon-γ release assay Covi-FERON FIA. Patients were interviewed for breakthrough COVID-19 infection (BTI) 3 months post sampling. Sixty patients were studied after a median (IQR) of 179 (117-221.5) days from last vaccine to sampling. Forty (66.7%) patients had positive Covi-FERON and 23 (38.3%) had detectable anti-spike IgG. Covi-FERON positive patients had lower median RTX cumulative dose [6 (4-10.75) vs 11 (6.75-14.75) grams, (P = 0.019)]. Patients with positive anti-spike IgG had received fewer RTX cycles [2 (2-4) vs 6 (4-8), P = 0.002] and cumulative dose [4 (3-7) vs 10 (6.25-13) grams, P = 0.002] and had shorter time from last vaccination to sampling [140 (76-199) vs 192 (128-230) days, P = 0.047]. Thirty-seven percent were positive only for Covi-FERON and 7% only for anti-spike IgG. Twenty (33.3%) BTI occurred post sampling, exclusively during Omicron variant predominance. The proportion of patients with CMI response against Delta variant was lower in patients who experienced BTI (25% vs 55%, P = 0.03). Four out of ten RTX-treated vaccinated patients show lasting cell-mediated immune response despite undetectable anti-spike antibodies. Cumulative RTX dose affects both humoral and cell-mediated responses to SARS-CoV-2 vaccines. Cell-mediated immune responses call for attention as a vaccine efficacy marker against SARS-CoV-2.

Biologics in Rheumatoid Arthritis: When &amp; Why?

Among the autoimmune rheumatic diseases RA is common. Not only articular extra-articular manifestations are common including involvement of skin, ocular, haematological, pulmonary and renal systems. A heightened cardiovascular risk also exists which closely follows disease activity stresses to obtain remission or low disease activity. Therapeutic landscape of RA treatment most significantly shiftedwith the introduction of biological disease modifying anti-rheumatic drugs (bDMARDs). There are five classes of bDMARDs currently available, each with a different molecular target and subtle differences in their efficacy and safety profile. Patient with poor prognostic factors and failed to csDMARDs are the candidate of anti-TNF agents and or other biologics. Clinicians should screen for latent infections with hepatitis B and C serology, chest radiograph plus interferon gamma release assay or tuberculin skin test. In the indicated cases, HIV serology should be requested as well. To reduce infection risk, guidelines specify that patients on bDMARDs should continue with national vaccination schedules including influenza and pneumococcal immunisations as well as the HPV vaccine for cervical cancer. Live attenuated vaccines (like, live herpes zoster vaccine, yellow fever, measles, mumps, rubella), are contraindicated in patients taking a bDMARD. The contraindications of anti-TNF agent’s initiations are serious or untreated infections including TB, current malignancy, multiple sclerosis, severe heart failure and hypersensitivity. In case of tocilizumab contraindications are serious or untreated infections, hypersensitivity and diverticulitisand for rituximab reactivation of hepatitis B.Coadministration of one class of bDMARD with another from a different class is not recommended due to an increased risk of infection. A DAS28 reduction of &lt;1.2 should be considered as improvement at 3 and 6 monthvisits. A close monitoring is advocated for the adverse effects of biologic agents. TNF inhibitors may be continued during pregnancy. Rituximab, abatacept and IL-6 inhibitors are not safe in first trimester. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 193-194

Invited Commentary: The Winding Road to Identifying the Annual Rate of Tuberculosis Infection.

Many persons with immunological tests indicating Mycobacterium tuberculosis infection, such as tuberculin skin tests or interferon-γ release assays, are at risk of progression to tuberculosis disease. Persons whose tests revert to negative may no longer be at such risk. Therefore, identifying the rate of test reversion, potentially indicating cure of M. tuberculosis infection, is an important area of investigation. In their accompanying article (Am J Epidemiol. 2023;192(12):1937-1943), Schwalb et al. extract data on test reversion from prechemotherapy literature and construct a model to predict the rate of reversion, and thus the likely cure of infection. Unfortunately, the incompleteness of the historical data and the use of imprecise definitions of test positivity and reversion lead to substantial misclassification and limit the usefulness of the model. Better definitions and improved tests will be needed in order to develop a clear picture of this aspect of the natural history of tuberculosis.

The Best Method for CMV Prevention in High-risk Kidney Transplant Recipients? Either, per National Norwegian Transplant Database: Commentary on Blom et al, Cytomegalovirus High-risk Kidney Transplant Recipients Show No Difference in Long-term Outcomes Following Preemptive Versus Prophylactic Management.

The Best Method for CMV Prevention in High-risk Kidney Transplant Recipients? Either, per National Norwegian Transplant Database: Commentary on Blom et al, Cytomegalovirus High-risk Kidney Transplant Recipients Show No Difference in Long-term Outcomes Following Preemptive Versus Prophylactic Management.

Relationship between ambient temperature at sampling and the interferon gamma test result for bovine tuberculosis in cattle

Bovine tuberculosis (bTB) is a disease of significant economic and zoonotic importance, therefore, optimising tests for the identification of Mycobacterium bovis infected cattle is essential. The Interferon Gamma (IFN-γ) Release Assay (IGRA) can diagnose M. bovis infected cattle at an early stage, is easy to perform and can be used alongside skin tests for confirmatory purposes or to increase diagnostic sensitivity. It is known that IGRA performance is sensitive to environmental conditions under which samples are taken and transported. In this study, the association between the ambient temperature on the day of bleeding and the subsequent IGRA result for bTB was quantified using field samples from Northern Ireland (NI). Results of 106,434 IGRA results (2013–2018) were associated with temperature data extracted from weather stations near tested cattle herds. Model dependent variables were the levels of IFN-γ triggered by avian purified protein derivative (PPDa), M. bovis PPD (PPDb), their difference (PPD(b-a)) as well as the final binary outcome (positive or negative for M. bovis infection). IFN-γ levels after both PPDa and PPDb stimulation were lowest at the extremes of the temperature distribution for NI. The highest IGRA positive probability (above 6%) was found on days with moderate maximum temperatures (6–16 °C) or moderate minimum temperatures (4–7 °C). Adjustment for covariates did not lead to major changes in the model estimates. These data suggest that IGRA performance can be affected when samples are taken at high or low temperatures. Whilst it is difficult to exclude physiological factors, the data nonetheless supports the temperature control of samples from bleeding through to laboratory to help mitigate post-collection confounders.

Performance of two interferon-gamma release assays for tuberculosis infection screening in Kawasaki children before immunosuppressive therapy.

We aimed to compare QuantiFERON-TB Gold In-Tube (QFT-GIT) and X.DOT-TB for screening latent tuberculosis infection (LTBI) in kawasaki patients, and to identify the risk factors associated with indeterminate IGRA results. We conducted a retrospective study on children with KD, who were screened for mycobacterium tuberculosis (Mtb) infection by either ELISA-based QFT-GIT or ELISPOT-based X.DOT-TB tests, admitted in Department of Cardiology, Beijing Children's Hospital from July 2019 to April 2022. A total of 1327 cases were included. Among them, 932 cases were tested by QFT-GIT and 395 cases by X.DOT-TB. The positive rate of children was 0.1% and 0.2%, and the indeterminate rate was 68.2% and 6.1% for QFT-GIT and X.DOT-TB, respectively. Patients with hypoproteinemia had a higher risk of indeterminate X.DOT-TB result. Female, critical ill, shock or hypoproteinemia presented statistically significant associations with an increased risk of indeterminate QFT-GIT result. High-dose of IVIG inhibited the release of IFN-γ by more than 90%, which might account for the high indeterminate incidence. It is recommended to perform X.DOT-TB rather than QFT-GIT to screen LTBI in patients with high level of the mitogen that can inhibit IFN-γ release. For KD children with positive IGRA results, it has a higher risk of activation TB infection when treated with immunosuppressive therapy in the future. Children with KD aged <5 years old had higher frequency of indeterminate IGRA results.

Withdrawal Notice: The Performance of Interferon-gamma Release Assays and Tuberculin Skin Tests in the Diagnosis of Latent Tuberculosis Infection among Immune-mediated Inflammatory Diseases: A Meta-analysis Study

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Indeterminate results of interferon gamma release assays in the screening of latent tuberculosis infection: a systematic review and meta-analysis.

We aimed to evaluate the indeterminate rate of interferon gamma release assays (IGRAs) in the detection of latent tuberculosis infection (LTBI). On 15 November 2022, we searched the PubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), and Cochrane Library databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two investigators independently extracted the study data and assessed their quality using a modified quality assessment of diagnostic accuracy studies (i.e., QUADAS-2) tool. A random-effects model was used to calculate pooled results. We included 403 studies involving 486,886 individuals and found that the pooled indeterminate rate was 3.9% (95% CI 3.5%-4.2%). The pooled indeterminate rate for QuantiFERON®-TB (QFT) was similar to that for T-SPOT®.TB (T-SPOT) [odds ratio (OR)=0.88, 95% CI 0.59-1.32]; however, the indeterminate rate for a new generation of QFT (QFT-plus) was lower than that of T-SPOT (OR=0.24, 95% CI 0.16-0.35). The indeterminate rate in the immunocompromised population was significantly higher than that in healthy controls (OR=3.51, 95% CI 2.11-5.82), and it increased with the reduction of CD4+ cell count in HIV-positive patients. Children's pooled indeterminate rates (OR=2.56, 95% CI 1.79-3.57) were significantly higher than those of adults, and the rates increased as the children's age decreased. On average, 1 in 26 tests yields indeterminate IGRA results in LTBI screening. The use of advanced versions of the QuantiFERON-TB assay (QFT-plus), may potentially reduce the occurrence of an indeterminate result. Our study emphasizes the high risk of immunosuppression and young age in relation to indeterminate IGRA, which should receive more attention in the management of LTBI. PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020211363, CRD42020211363.

Robust Vaccine-Induced as Well as Hybrid B- and T-Cell Immunity across SARS-CoV-2 Vaccine Platforms in People with HIV.

Few studies have comprehensively compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced and hybrid B- and T-cell responses in people with HIV (PWH) to those in comparable controls without HIV. We included 195 PWH and 246 comparable controls from the AGEhIV COVID-19 substudy. A positive nucleocapsid antibody (INgezim IgA/IgM/IgG) or self-reported PCR test defined prior SARS-CoV-2 infection. SARS-CoV-2 anti-spike (anti-S) IgG titers and anti-S IgG production by memory B cells were assessed. Neutralizing antibody titers were determined in a subset of participants. T-cell responses were assessed by gamma interferon (IFN-γ) release and activation-induced marker assay. We estimated mean differences in postvaccination immune responses (β) between levels of determinants. Anti-S IgG titers and anti-S IgG production by memory B cells were not different between PWH and controls. Prior SARS-CoV-2 infection (β = 0.77), receiving mRNA vaccine (β = 0.56), female sex (β = 0.24), fewer days between last vaccination and sampling (β = 0.07), and a CD4/CD8 ratio of <1.0 (β = -0.39) were independently associated with anti-S IgG titers, but HIV status was not. Neutralization titers against the ancestral and Delta and Omicron SARS-CoV-2 variants were not different between PWH and controls. IFN-γ release was higher in PWH. Prior SARS-CoV-2 infection (β = 2.39), HIV-positive status (β = 1.61), and fewer days between last vaccination and sampling (β = 0.23) were independently associated with higher IFN-γ release. The percentages of SARS-CoV-2-reactive CD4+ and CD8+ T cells, however, were not different between PWH and controls. Individuals with well-controlled HIV generally mount robust vaccine-induced as well as hybrid B- and T-cell immunity across SARS-CoV-2 vaccine platforms similar to controls. Determinants of a reduced vaccine response were likewise largely similar in both groups and included a lower CD4/CD8 ratio. IMPORTANCE Some studies have suggested that people with HIV may respond less well to vaccines against SARS-CoV-2. We comprehensively compared B- and T-cell responses to different COVID-19 vaccines in middle-aged persons with well-treated HIV and individuals of the same age without HIV, who were also highly comparable in terms of demographics and lifestyle, including those with prior SARS-CoV-2 infection. Individuals with HIV generally mounted equally robust immunity to the different vaccines. Even stronger immunity was observed in both groups after prior SARS-CoV-2 infection. These findings are reassuring with respect to the efficacy of SARS-Cov-2 vaccines for the sizable and increasing global population of people with HIV with access and a good response to HIV treatment.

Bottlenecks and recent advancements in detecting Mycobacterium tuberculosis in patients with HIV

AbstractTuberculosis (TB) remains a leading cause of deaths among patients with acquired immunodeficiency syndrome patients. Early diagnosis of TB is essential for administering timely anti‐TB therapy and improving health outcomes, particularly in the people living with HIV. However, conventional techniques used to detect Mycobacterium tuberculosis have significant drawbacks: for example, sputum smear microscopy has low sensitivity, and liquid culture is time‐consuming in patients with HIV‐TB co‐infection due to low sputum production. In addition, while immunological‐based methods involving tuberculin skin testing and interferon gamma release assays are commonly used for auxiliary TB diagnosis, they are often inaccurate in immunodeficient patients. Molecular techniques such as line probe assays, Xpert MTB, and lipoarabinomannan assay are recommended for early diagnosis by World Health Organization. However, no single technique is sufficicent for diagnosing HIV/TB co‐infection, suggesting that multiple diagnostic tests should be used to detect TB. Here, we summarize the drawbacks and advantages of existing TB‐diagnostic methods, as well as their applications to diagnosing HIV/TB co‐infection. We describe newly emerging technologies such as whole genome sequencing and mass spectrometry, with the aim of providing updated guidelines and alternative strategies for TB diagnosis, and particularly HIV/TB diagnosis.

Examining Test Cutoffs to Optimize Diagnosis of Latent Tuberculosis Infection in People Born Outside the United States.

Rationale: Detection of latent tuberculosis infection (LTBI) in persons born in high tuberculosis (TB) incidence countries living in low TB incidence countries is key to TB elimination in low-incidence countries. Optimizing LTBI tests is critical to targeting treatment. Objectives: To compare the sensitivity and specificity of tuberculin skin test (TST) and two interferon-γ release assays at different cutoffs and of a single test versus dual testing. Methods: We examined a subset (N = 14,167) of a prospective cohort of people in the United States tested for LTBI. We included non-U.S.-born, human immunodeficiency virus-seronegative people ages 5 years and older with valid TST, QuantiFERON-TB Gold-in-Tube (QFT), and T-SPOT.TB (TSPOT) results. The sensitivity/specificity of different test cutoffs and test combinations, obtained from a Bayesian latent class model, were used to construct receiver operating characteristic (ROC) curves and assess the area under the curve (AUC) for each test. The sensitivity/specificity of dual testing was calculated. Results: The AUC of the TST ROC curve was 0.81 (95% credible interval (CrI), 0.78-0.86), with sensitivity/specificity at cutoffs of 5, 10, and 15 mm of 86.5%/61.6%, 81.7%/71.3%, and 55.6%/88.0%, respectively. The AUC of the QFT ROC curve was 0.89 (95% CrI, 0.86-0.93), with sensitivity/specificity at cutoffs of 0.35, 0.7, and 1.0 IU/mL of 77.7%/98.3%, 66.9%/99.1%, and 61.5%/99.4%. The AUC of the TSPOT ROC curve was 0.92 (95% CrI, 0.88-0.96) with sensitivity/specificity for five, six, seven, and eight spots of 79.2%/96.7%, 76.8%/97.7%, 74.0%/98.6%, and 71.8%/99.5%. Sensitivity/specificity of TST-QFT, TST-TSPOT, and QFT-TSPOT at standard cutoffs were 73.1%/99.4%, 64.8%/99.8%, and 65.3%/100%. Conclusion: Interferon-γ release assays have a better predictive ability than TST in people at high risk of LTBI.

Tuberculin skin tests and interferon-γ release assays in the diagnosis of tuberculosis infection.

Tuberculin skin tests and interferon-γ release assays in the diagnosis of tuberculosis infection.

A solitary intracranial rich focus with early meningeal involvement: A correlative image

•Rich foci are caseating brain tuberculous (TB) granulomas surrounding the immigrated TB bacilli.•Rich foci are hypothesized as an underlying pathological mechanism of TB meningitis.•The hypothesis is based on necropsy studies and has rarely been depicted in vivo.•Ruptured foci discharge their contents into the neighboring subarachnoid space.•Discharged contents trigger a T cell response, leading to inflammatory meningitis. A 24-year-old man presented to the emergency department with a 2-day history of fever and headache, not responsive to over-the-counter medications. He reported a previous history of latent tuberculosis, for which he received antitubercular therapy a couple of years ago. Positive results were obtained from interferon-γ release and adenosine deaminase (ADA) assays, but chest computed tomography (CT) was unremarkable. The patient had unremarkable general and neurologic examinations. Brain CT demonstrated a left-sided focal lesion that delineates perfectly post-contrast administration, besides an adjacent area of meningeal enhancement at the Sylvian sulcus (Figure 1). Cerebrospinal fluid analysis revealed monocytic pleocytosis, an elevated protein level, marked hypoglycorrhachia, and positive ADA activity. Based on the data obtained thus far, we concluded that the patient had an early focal tuberculous meningitis (TBM) caused by a rupturing rich focus, consistent with the natural history of TBM that has rarely been confirmed in vivo (Supplement 1) [1Rich AR McCordock HA. Evidence for the presence of ribonucleic acid in the cytoplasmic bodies that appear in the hepatic and adrenal epithelial cells of man in acute infection.Bull Johns Hopkins Hosp. 1933; 52: 5-37Google Scholar, 2Donald PR Schaaf HS Schoeman JF. Tuberculous meningitis and miliary tuberculosis: the Rich focus revisited.J Infect. 2005; 50: 193-195https://doi.org/10.1016/j.jinf.2004.02.010Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar, 3Be NA Kim KS Bishai WR Jain SK. Pathogenesis of central nervous system tuberculosis.Curr Mol Med. 2009; 9: 94-99https://doi.org/10.2174/156652409787581655Crossref PubMed Scopus (100) Google Scholar]. Subsequently, the patient was started on antitubercular treatment using INH, RIF, PZA, and EMB for 2 months. After which, PZA and EMB were discontinued, while INH and RIF were continued for an additional nine months. The focus with the associated TBM resolved substantially following treatment with no evidence of recurrence over a 2-year follow-up.

Plasma chemokines CXCL10 and CXCL9 as potential diagnostic markers of drug-sensitive and drug-resistant tuberculosis

Tuberculosis (TB) diagnosis still remains to be a challenge with the currently used immune based diagnostic methods particularly Interferon Gamma Release Assay due to the sensitivity issues and their inability in differentiating stages of TB infection. Immune markers are valuable sources for understanding disease biology and are easily accessible. Chemokines, the stimulant, and the shaper of host immune responses are the vital hub for disease mediated dysregulation and their varied levels in TB disease are considered as an important marker to define the disease status. Hence, we wanted to examine the levels of chemokines among the individuals with drug-resistant, drug-sensitive, and latent TB compared to healthy individuals. Our results demonstrated that the differential levels of chemokines between the study groups and revealed that CXCL10 and CXCL9 as potential markers of drug-resistant and drug-sensitive TB with better stage discriminating abilities.

Prevalence and predictors of tuberculosis infection among people living with HIV in a high tuberculosis burden context

BackgroundTuberculosis (TB) disease is the leading cause of mortality among people living with HIV (PLHIV). Interferon-gamma release assays (IGRAs) are approved for TB infection ascertainment. However, current IGRA data on...

Prevalence of latent Mycobacterium tuberculosis infection in hematopoietic stem cell transplantation comparing tuberculin skin test and interferon-gamma release assay.

The aim of this study was to evaluate the prevalence of latent Mycobacterium tuberculosis infection in hematopoietic stem cell transplantation candidates, using tuberculin skin test and QuantiFERON-TB Gold-Plus, in a high-burden tuberculosis country. Adult candidates for hematopoietic stem cell transplantation performed both tests before and those submitted to transplantation were followed up for 12 months. The prevalence of latent Mycobacterium tuberculosis infection was 17.1% and a moderate agreement between QuantiFERON-TB Gold-Plus and tuberculin skin test was observed in this population. Previous tuberculosis exposure was a risk factor for latent Mycobacterium tuberculosis infection. No cases of tuberculosis were diagnosed during follow-up period.

Anti-interferon-γ autoantibodies in patients with indeterminate QuantiFERON®-TB Gold Plus Assay results

BackgroundThe QuantiFERON®-TB Gold Plus Assay (QFT-G), a commercial interferon-γ (IFNγ) release assay, is used to screen patients for latent tuberculosis infection. Although anti-IFN-γ autoantibodies (Abs) have been recognized to cause indeterminate results, the prevalence and neutralizing capacity of these autoantibodies in general population indeterminate samples are unknown. ObjectivesWe sought to determine whether anti-IFN-γ autoantibodies accounted for indeterminate results in the QFT-G Assay.Design/Methods: Patient plasmas from the nil tube of the QFT-G were screened in a blinded fashion for IFN-γ antibodies using a particle-based approach. Samples were from TB positive, TB negative, and indeterminate samples. Binding activity of IgG to IFNγ was determined as a function of fluorescence intensity. Neutralizing capacity as a measure of antibody function was assessed by intranuclear staining of normal peripheral blood mononuclear cells (PBMCs) for IFNγ-induced pSTAT-1 in the presence of patient plasma. ResultsWe screened 537 patient plasmas (151 positive, 352 negative, 34 indeterminate) for anti-IFN-γ Abs from the nil tubes of QFT-G. Of those screened, 14 samples had binding activity to IFNγ. Three samples with high-titer anti-IFN-γ Abs (> mean plus three standard deviations of healthy control samples) neutralized IFNγ in vitro. Two of these samples were indeterminate, and 1 QFT-G negative. Therefore, of 14 samples with anti- IFNγ binding activity, 3 were neutralizing and 2 of those were indeterminate in QFT-G. ConclusionsAnti-IFN-γ autoantibodies were found in approximately 3% of plasmas submitted to a commercial laboratory. Of the 14 samples with binding activity for IFNγ, only 3 were fully neutralizing, and 2 of those occurred in the indeterminate group, accounting for 5% of all indeterminate samples. Anti-IFN-γ Abs are not rare in the population undergoing QFT-G testing and some of these autoantibodies are neutralizing and can affect the result of the assay.

Combined Detection of IFN-γ and Lymphocyte Subsets with Activation Indicators in the Clinical Application of Mycobacterium Tuberculosis Infection at Different Times

The immune status of mycobacterium tuberculosis (MTB) infection is essential for the diagnosis and treatment of this disease. In this work, we aim to evaluate the clinical significance of the combination of serum IFN-γ, IGRAs (Interferon-Gamma Release Assay), lymphocyte subset with activation indicators detection in active and latent tuberculosis infection patients. For this study, anticoagulant whole blood were collected from 45 active tuberculosis (AT group), 44 latent tuberculosis (LT group) and 32 healthy controls (HCs group). The serum IFN-γ and IGRAs detected by chemiluminescence, and the percentage of lymphocyte subsets and activated lymphocytes detected by flow cytometry. The results showed combined IGRAs, serum IFN-γ and NKT cells not only has good diagnostic efficiency for the AT, but also provides a laboratory diagnostic method to distinguish AT from LT. Activation indicator of CD3+HLA-DR+T and CD4+HLA-DR+T can effectively distinguish LT from HCs. While combined CD3+T, CD4+T, CD8+CD28+T, Treg and CD16+CD56+CD69+ cells can distinguish AT from HCs. This study showed combined direct detection of serum IFN-γ and IGRAs as well as lymphocyte subsets with activation indicators which may provide laboratory basis for the diagnosis and differential diagnosis of active and latent MTB infection.

Diagnosis and treatment of tuberculosis presenting as uveitis based on stochastic simulation in systems biology

ABSTRACT Tuberculous uveitis can be a manifestation of extrapulmonary tuberculosis or an allergic reaction to tuberculosis infection. The clinical signs and symptoms of other uveitis causes are generic, making a false diagnosis simple. We present a brief introduction to theoretical modelling and simulation in systems biology and explore the consequences of TB uveitis if left untreated. Patients were admitted to our hospital with recurrent fever. They had a previous definitive diagnosis of binocular uveitis and a positive interferon gamma release assay (IGRA) test result. At the time, there was no antituberculosis medicine available, and immunosuppressive and glucocorticoid therapy did not work. After the admission, their pleural fluid tested positive for Mycobacterium tuberculosis. No other causes to explain the fever were found. A diagnosis of tuberculosis was made, and their body temperature normalized after antituberculosis treatment and closed chest drainage. Vigilance should be exercised to rule out tuberculous uveitis in cases of unexplained uveitis; this calls for IGRA screening, tuberculin skin testing, and cyst imaging. For patients with latent tuberculosis infections, it is recommended to administer antituberculosis treatment, after excluding other possible causes, and to avoid using glucocorticoids in isolation.