Longitudinal Mycobacterium tuberculosis specific interferon-γ responses in Ethiopian HIV-negative women during pregnancy and post-partum

Background: Pregnancy may influence cellular immune responses to Mycobacterium tuberculosis (Mtb). We investigated Mtb-specific interferon-γ responses in women followed longitudinally during pregnancy and post-partum. Methods: Interferon-γ levels (stimulated by Mtb 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 TB with Mtb-triggered interferon-γ responses ≥0.20 IU/ml, sampled on two and/or three occasions (1 st /2 nd trimester, 3 rd trimester and 9 months post-partum). Results: Among 2093 women in the source cohort, 363 met inclusion criteria for longitudinal comparisons of Mtb-stimulated interferon-γ responses. Median Mtb-triggered interferon-γ concentrations were higher at 3 rd compared to 1 st /2 nd trimester (in 38 women with samples available from these timepoints; TB1: 2.8 vs 1.6 IU/ml, p=0.005; TB2: 3.3 vs 2.8 IU/ml, p=0.03) and post-partum (in 49 women with samples available from these timepoints; TB1: 3.1 vs 2.2 IU/ml, p=0.01; TB2: 3.1 vs 2.3 IU/ml, p=0.03). In contrast, mitogen-stimulated interferon-γ levels were lower at 3 rd compared with 1 st /2 nd trimester (in 32 women with samples available from these timepoints: 21.0 vs 34.9 IU/ml, p=0.02). Results were similar in 22 women sampled on all three occasions. Conclusions: In HIV-negative women, Mtb-stimulated interferon-γ responses were higher during the 3 rd trimester compared to earlier stages of pregnancy and post-partum, despite decreased mitogen-triggered responses. These findings suggest increased Mtb-specific cellular responses due to dynamic changes of latent TB infection during pregnancy.

Download Full-text

Recent Progress in Diagnosis Methods for Latent Tuberculosis Infection and Its Clinical Applications

Infection International ◽

10.1515/ii-2017-0110 ◽

2015 ◽

Vol 4 (3) ◽

pp. 69-74

Author(s):

Ling Zhou

Keyword(s):

Mycobacterium Tuberculosis ◽

Recent Progress ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Interferon Γ ◽

Clinical Applications ◽

Active Tuberculosis ◽

Advantages And Disadvantages ◽

Latent Tb ◽

Latent Tb Infection

AbstractMost people with latentMycobacterium tuberculosisinfection can partly develop active tuberculosis (TB). Therefore, diagnosis of this condition bears significance in early TB prevention. To date, the main methods for diagnosis of latent TB infection (LTBI) include tuberculin skin test and interferon γ release test. These two methods feature their own advantages and disadvantages. Although new diagnostic markers continually emerge, no uniform diagnostic criteria are available for TB detection. This study summarizes several methods for diagnosis of LTBI and new related markers and their application value in clinical practice.

Download Full-text

Cellular Immune Responses in HIV-Negative Immunodeficiency with Anti-Interferon-γ Antibodies and Opportunistic Intracellular Microorganisms

PLoS ONE ◽

10.1371/journal.pone.0110276 ◽

2014 ◽

Vol 9 (10) ◽

pp. e110276 ◽

Cited By ~ 5

Author(s):

Jiraprapa Wipasa ◽

Panuwat Wongkulab ◽

Kriangkrai Chawansuntati ◽

Romanee Chaiwarit ◽

Khuanchai Supparatpinyo

Keyword(s):

Immune Responses ◽

Interferon Γ ◽

Cellular Immune Responses ◽

Cellular Immune ◽

Hiv Negative

Download Full-text

Comparison of Screening Procedures for Mycobacterium tuberculosis Infection Among Patients with Inflammatory Diseases

The Journal of Rheumatology ◽

10.3899/jrheum.081292 ◽

2009 ◽

Vol 36 (9) ◽

pp. 1876-1884 ◽

Cited By ~ 38

Author(s):

BOLETTE SOBORG ◽

MORTEN RUHWALD ◽

MERETE LUND HETLAND ◽

SØREN JACOBSEN ◽

AASE BENGAARD ANDERSEN ◽

...

Keyword(s):

Risk Factors ◽

Mycobacterium Tuberculosis ◽

Inflammatory Diseases ◽

Interferon Γ ◽

Mycobacterium Tuberculosis Infection ◽

Tb Treatment ◽

Latent Tb ◽

Latent Tb Infection ◽

High Degree

Objective.To test if Mycobacterium tuberculosis screening results differ among patients with inflammatory disease depending on whether the QuantiFeron TB-Gold test (QFT) or tuberculin skin test (TST) is used; and to evaluate if a possible difference is influenced by the presence of risk factors or immunosuppression.Methods.The interferon-γ response to in vitro stimulation of M. tuberculosis-specific antigens was measured with QFT and results were compared with TST. Associations to bacillus Calmette-Guerin (BCG) vaccination, risk factors, and immunosuppression were analyzed for both tests.Results.QFT and TST results were available for 294/302 and 241/302 patients, respectively; 234 had results from both tests. Twenty-one (7%) tested positive with QFT and 45 (19%) with TST. A positive QFT was associated with risk factors for M. tuberculosis infection: i.e., birth or upbringing in a TB-endemic area [risk ratio (RR) = 7.8, 95% CI 1.5–18.2, p < 0.001], previous TB treatment (RR 4.7, 95% CI 1.6–13.5, p = 0.005), and any latent TB infection risk factor (RR 4.7, 95% CI 2.1–11.0, p = 0.0002). Treatment with corticosteroids increased the risk for an inconclusive QFT result (RR 4.2, 95% CI 1.6–10.7, p = 0.04) and decreased the risk for a positive TST result (RR 0.4, 95% CI 0.1–1.0, p = 0.04). Agreement between the tests was low (kappa 0.2, 95% CI 0.02–0.3, p = 0.002).Conclusion.The study documented a high degree of discordant positive QFT and TST results. A positive QFT was more closely associated with risk factors for M. tuberculosis infection than the TST. The use of corticosteroids affected test outcome by increasing the risk for an inconclusive QFT result and decreasing the risk for a positive TST result.

Download Full-text

DYNAMIC CHANGES OF GRANULYSIN AND CATHELICIDIN IN CHILDREN AND ADOLESCENTS WITH DIFFERENT FORMS OF PULMONARY TUBERCULOSIS

Medical Immunology (Russia) ◽

10.15789/1563-0625-2018-5-747-752 ◽

2018 ◽

Vol 20 (5) ◽

pp. 747-752

Author(s):

M. M. (Jr) Averbakh ◽

L. V. Panova ◽

M. F. Gubkina ◽

N. I. Evseeva

Keyword(s):

Mycobacterium Tuberculosis ◽

Immune System ◽

Children And Adolescents ◽

Innate Immune System ◽

Original Data ◽

Innate Immune ◽

Dynamic Changes ◽

Latent Tb ◽

Baseline Values ◽

Latent Tb Infection

Granulysin and cathelicidin, the cytolytic molecules of innate immune system are important protective factors during infection with Mycobacterium tuberculosis. We present original data concerning high levels of granulysin and cathelicidin among the group of children and adolescents with latent TB infection. Patients with tuberculosis of the respiratory system exhibit significantly lower amounts of serum cathelicidin in destructive forms, as well as granulysin levels in “minor” forms of tuberculosis before starting the specific chemotherapy. The chemotherapy performed did not influence the serum granulysin and cathelicidin contents in patients with destructive tuberculosis, whereas the patients with “minor” forms (TLN/focal tuberculosis) revealed a significant increase in granulysin content after 6 months of treatment, and same trend for cathelicidin concentrations after 3 months of chemotherapy, followed by subsequent return to baseline values.

Download Full-text

Cellular Immune Responses to Nine Mycobacterium tuberculosis Vaccine Candidates following Intranasal Vaccination

PLoS ONE ◽

10.1371/journal.pone.0022718 ◽

2011 ◽

Vol 6 (7) ◽

pp. e22718 ◽

Cited By ~ 22

Author(s):

Suraj B. Sable ◽

Mani Cheruvu ◽

Subhadra Nandakumar ◽

Sunita Sharma ◽

Kakali Bandyopadhyay ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Vaccine Candidates ◽

Cellular Immune Responses ◽

Cellular Immune

Download Full-text

The Mycobacterium tuberculosis Recombinant 27-Kilodalton Lipoprotein Induces a Strong Th1-Type Immune Response Deleterious to Protection

Infection and Immunity ◽

10.1128/iai.71.6.3146-3154.2003 ◽

2003 ◽

Vol 71 (6) ◽

pp. 3146-3154 ◽

Cited By ~ 55

Author(s):

Avi-Hai Hovav ◽

Jacob Mullerad ◽

Liuba Davidovitch ◽

Yolanta Fishman ◽

Fabiana Bigi ◽

...

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Interleukin 10 ◽

Control Groups ◽

Cellular Immune Responses ◽

Protective Antigens ◽

Proliferation Response ◽

Cellular Immune ◽

Mycobacterial Antigens

ABSTRACT Th1 immune response is essential in the protection against mycobacterial intracellular pathogens. Lipoproteins trigger both humoral and cellular immune responses and may be candidate protective antigens. We studied in BALB/c mice the immunogenicity and the protection offered by the recombinant 27-kDa Mycobacterium tuberculosis lipoprotein and the corresponding DNA vaccine. Immunization with the 27-kDa antigen resulted in high titers of immunoglobulin G1 (IgG1) and IgG2a with a typical Th1 profile and a strong delayed hypersensitivity response. A strong proliferation response was observed in splenocytes, and significant nitric oxide production and gamma interferon secretion but not interleukin 10 secretion were measured. Based on these criteria, the 27-kDa antigen induced a typical Th1-type immune response thought to be necessary for protection. Surprisingly, in 27-kDa-vaccinated mice (protein or DNA vaccines) challenged by M. tuberculosis H37Rv or BCG strains, there was a significant increase in the numbers of CFU in the spleen compared to that for control groups. Furthermore, the protection provided by BCG or other mycobacterial antigens was completely abolished once the 27-kDa antigen was added to the vaccine preparations. This study indicates that the 27-kDa antigen has an adverse effect on the protection afforded by recognized vaccines. We are currently studying how the 27-kDa antigen modulates the mouse immune response.

Download Full-text

Modulatory effects of interferon-γ and interleukin-4 on cellular immune responses againstHypoderma lineatumantigens

Medical and Veterinary Entomology ◽

10.1111/mve.12190 ◽

2016 ◽

Vol 30 (4) ◽

pp. 439-443

Author(s):

E. CABANELAS ◽

C. M. LÓPEZ ◽

P. DÍAZ ◽

A. PÉREZ -CREO ◽

P. MORRONDO ◽

...

Keyword(s):

Immune Responses ◽

Interferon Γ ◽

Interleukin 4 ◽

Cellular Immune Responses ◽

Cellular Immune

Download Full-text

Gluthathione S-transferase-resuscitation-promoting factor B recombinant protein of Mycobacterium tuberculosis induces the production of interferon-γ and interleukin-12 in mice splenocytes

Medical Journal of Indonesia ◽

10.13181/mji.v28i3.2444 ◽

2019 ◽

Vol 28 (3) ◽

pp. 234-40

Author(s):

Andriansjah Rukmana ◽

Burhanuddin Rasyid ◽

Fitriyah Sjatha

Keyword(s):

Mycobacterium Tuberculosis ◽

Recombinant Protein ◽

Polyacrylamide Gel Electrophoresis ◽

Sodium Dodecyl ◽

Interferon Γ ◽

Interleukin 12 ◽

Potential Candidate ◽

Factor B ◽

Latent Tb

BACKGROUND As the only TB vaccine available, Bacillus Calmette-Guérin shows variable efficacy in adults and does not provide protection against the resuscitation of latent TB infections. Resuscitation-promoting factor B (RpfB) is a protein produced by Mycobacterium tuberculosis during the resuscitation phase and is promising as a novel TB vaccine. This study was aimed to analyze the immunogenicity of the gluthathione S-transferase (GST)-RpfB recombinant protein on mice splenocytes in vitro. METHODS After induction with isopropyl β-D-1-thiogalactopyranoside, the protein was extracted by sonication followed by solubilization in 8 M urea buffer. Protein was then re-natured and purified with a GST chromatography column. The isolated protein was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot using anti-GST antibodies, and its concentration was determined using the Bradford method. Each group of splenocytes was treated with 25 μg/ ml of the recombinant protein (GST-RpfB), GST, and phytohemagglutinin. Antigen induction was repeated twice at 24 and 72 hours. The supernatant was collected at 96 hours and interferon gamma (IFNγ), interleukin (IL-12, IL-4, and IL-10) levels were measured with enzyme-linked immunosorbent assays. RESULTS GST-RpfB recombinant proteins were expressed in the form of inclusion bodies with a molecular weight of approximately 66 kDa. Based on the independent t-test, GST-RpfB stimulated IFNγ and IL-12 production but not IL-4 and IL-10. CONCLUSIONS The GST-RpfB protein has been immunogenically proven and is a potential candidate as a novel subunit TB vaccine.

Download Full-text

PO 8383 THE ROLE OF PLASMA B CELLS IN MYCOBACTERIUM TUBERCULOSIS INFECTION AND DISEASE

BMJ Global Health ◽

10.1136/bmjgh-2019-edc.80 ◽

2019 ◽

Vol 4 (Suppl 3) ◽

pp. A31.2-A31

Author(s):

Awa Gindeh ◽

Simon Donkor ◽

Olumuyiwa Owolabi

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

B Cells ◽

B Cell ◽

Bacterial Infections ◽

Relative Proportion ◽

Post Treatment ◽

Latent Tb ◽

Latent Tb Infection

BackgroundTuberculosis (TB) is still a major global health problem with about one-quarter of the global population infected with the causative pathogen, Mycobacterium tuberculosis (Mtb). The role of T-cells in the adaptive immune response against Mtb has been extensively studied with little information on the role of B-cells. B-cells produce antibodies and differentiate into plasma and memory B-cells. Plasmablasts are a subset of plasma cells only present in the peripheral circulation following an ongoing infection or vaccination. Immunoglobulin G(IgG) especially IgG2 mounts more efficient immune response against bacterial infections, mainly attributed to the high affinity of IgG2 binding to the Fcγ receptor. Therefore, we hypothesised that Mtb-specific IgG +plasmablasts may be a useful biomarker of TB infection status.MethodsEx-vivo B-cell enzyme-linked immunospot (ELISPOT) was used to identify plasmablasts responses to Mtb-specific antigens ESAT-6/CFP-10 (EC), together with non-specific Mtb purified protein derivative (PPD) and a positive (total IgG) and negative (media only) control from adults with active TB pre- and post-treatment (n=20) or with latent TB infection (LTBI; n=20) in The Gambia.ResultsFrequencies of Mtb-specific plasmablasts were significantly higher in active TB cases pre-treatment compared to post-treatment (p<0.0001) and LTBI with no difference seen following PPD stimulation. Interestingly, total IgG +cells were lower in the cases at recruitment but increased following treatment indicating the relative proportion of Mtb-specific responses were also significantly different (p=0.034) prior to therapy.ConclusionThese data show that B-cell responses are differentially modulated during active and latent TB infection, suggesting that plasmablasts may be a useful biomarker for TB infection in TB-endemic settings.

Download Full-text

First evaluation of QuantiFERON-TB Gold Plus performance in contact screening

European Respiratory Journal ◽

10.1183/13993003.00510-2016 ◽

2016 ◽

Vol 48 (5) ◽

pp. 1411-1419 ◽

Cited By ~ 68

Author(s):

Lucia Barcellini ◽

Emanuele Borroni ◽

James Brown ◽

Enrico Brunetti ◽

Daniela Campisi ◽

...

Keyword(s):

Index Case ◽

Interferon Γ ◽

Recent Infection ◽

Latently Infected ◽

Release Assay ◽

New Type ◽

Latent Tb ◽

The Difference ◽

Latent Tb Infection ◽

Surrogate Measures

Identifying latently infected individuals is crucial for the elimination of tuberculosis (TB). We evaluated for the first time the performance of a new type of interferon-γ release assay, QuantiFERON-TB Plus (QFT-Plus), which includes an additional antigen tube (TB2), stimulating both CD4+ and CD8+ T-cells in contacts of TB patients.Contacts were screened for latent TB infection by tuberculin skin test, QFT-Plus and QuantiFERON-TB Gold in Tube (QFT-GIT).In 119 TB contacts, the overall agreement between QFT-Plus and QFT-GIT was high, with a Cohen's κ of 0.8. Discordant results were found in 12 subjects with negative QFT-GIT and positive QFT-Plus results. In analyses of markers of TB exposure and test results, the average time spent with the index case was the strongest risk factor for positivity in each of these tests. The difference in interferon-γ production between the two antigen tubes (TB2−TB1) was used as an estimate of CD8+ stimulation provided by the TB2. TB2−TB1 values >0.6 IU·mL−1 were significantly associated with proximity to the index case and European origin.QFT-Plus has a stronger association with surrogate measures of TB exposure than QFT-GIT in adults screened for latent TB infection. Interferon-γ response in the new antigen tube used an indirect estimate of specific CD8+ response correlates with increased Mycobacterium tuberculosis exposure, suggesting a possible role in identifying individuals with recent infection.

Download Full-text