scholarly journals Retrospective Performance Analyses of over Two Million U.S. QuantiFERON Blood Sample Results

2021 ◽  
Author(s):  
Caixia Bi ◽  
Richard B. Clark ◽  
Ronald Master ◽  
Hema Kapoor ◽  
Martin H. Kroll ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Blood Sample ◽  
Interferon Gamma ◽  
Performance Data ◽  
Content Type ◽  
Test Systems ◽  
Ifn Γ ◽  
Performance Analyses

Both the QuantiFERON-TB Gold Plus (QFT-Plus) and the QuantiFERON-TB Gold In-Tube (QFT-GIT) tests are interferon gamma (IFN-γ) release assays (IGRAs) intended to detect in vitro cell-mediated immune responses to Mycobacterium tuberculosis antigens. In this study, we retrospectively analyzed performance data for both the QFT-GIT and QFT-Plus test systems from over 2 million samples.

scholarly journals PERCENTAGE OF CD3+ T LYMPHOCYTES EXPRESSING IFN-γ AFTER CFP-10 STIMULATION (Persentase Limfosit T-CD3+ yang Mengekspresikan Interferon Gamma Setelah Stimulasi Antigen CFP-10)

2018 ◽  
Vol 23 (1) ◽  
pp. 31
Author(s):  
Yulia Nadar Indrasari ◽  
Betty Agustina Tambunan ◽  
Jusak Nugraha ◽  
Fransiska Sri Oetami
Keyword(s):  
Flow Cytometry ◽  
Mycobacterium Tuberculosis ◽  
T Lymphocytes ◽  
Interferon Gamma ◽  
Tuberculosis Antigen ◽  
Mycobacterium Tuberculosis Antigen ◽  
Ifn Γ

Tuberkulosis (TB) merupakan penyakit infeksi menular, disebabkan oleh Mycobacterium tuberculosis. Respons imun adaptif yangdiperantarai oleh limfosit T berperan sangat penting dalam menyingkirkan bakteri intraseluler. Hasilan sitokin IFN-γ merupakanmekanisme efektor utama dari limfosit T. Pengembangan vaksin yang efektif dalam melawan infeksi TB mempertimbangkan faktor yangmengatur hasilan IFN-γ. CFP-10 merupakan antigen yang disekresikan oleh Mycobacterium tuberculosis. Antigen ini dikenal sebagaikomponen vaksin potensial untuk TB. Tujuan penelitian ini adalah membandingkan respons imun seluler yaitu persentase limfosit T-CD3+yang mengekspresikan IFN-γ setelah dirangsang antigen CFP-10 di pasien TB paru kasus baru, TB laten dan orang sehat. Penelitianini menggunakan desain eksperimen murni di laboratorium secara in vitro pada kultur PBMC pasien TB paru kasus baru, TB latendan orang sehat. Subjek penelitian adalah 8 pasien TB paru kasus baru, 7 TB laten dan 7 orang sehat di RS Khusus Paru Surabaya.Pemeriksaan persentase limfosit T-CD3+ yang mengekspresikan IFN-γ dengan metode Flow cytometry (BD FACSCalibur). Hasil dianalisisdengan Kruskal-Wallis atau ANOVA satu arah. Rerata persentase limfosit T-CD3+ yang mengekspresikan IFN-γ di TB paru kasus barusetelah stimulasi antigen CFP-10 (4,36%) lebih tinggi daripada sebelum stimulasi (3,50%) (nilai P=0,015). Rerata persentase limfositT-CD3+ yang mengekspresikan IFN-γ di TB laten setelah stimulasi antigen CFP-10 (3,96%) lebih tinggi dibandingkan sebelum stimulasi(2,50%) tetapi tidak bermakna (nilai P=0,367). Rerata persentase limfosit T- CD3+ yang mengekspresikan IFN-γ di orang sehat setelahstimulasi (1,66%) lebih rendah daripada sebelum stimulasi (2,89%) tetapi tidak bermakna (nilai P=0,199). Perubahan persentaselimfosit T-CD3+ yang mengekspresikan IFN-γ setelah stimulasi antigen CFP-10 antarkelompok tidak berbeda bermakna (nilai P=0,143).Berdasarkan hasil telitian ini dapat disimpulkan bahwa terdapat peningkatan persentase limfosit T-CD3+ yang mengekspresikan IFN-γdi TB paru kasus baru setelah stimulasi antigen CFP-10. Hal ini menunjukkan limfosit T-CD3+ yang mengekspresikan IFN-γ berperandalam perlindungan terhadap infeksi TB paru.

scholarly journals Immunostimulatory Effects of Recombinant Erysipelothrix rhusiopathiae Expressing Porcine Interleukin-18 in Mice and Pigs

2012 ◽  
Vol 19 (9) ◽  
pp. 1393-1398 ◽  
Author(s):  
Yohsuke Ogawa ◽  
Yu Minagawa ◽  
Fang Shi ◽  
Masahiro Eguchi ◽  
Yoshihiro Muneta ◽  
...  
Keyword(s):  
Immune Responses ◽  
Peritoneal Macrophages ◽  
Erysipelothrix Rhusiopathiae ◽  
Interleukin 18 ◽  
Murine Splenocytes ◽  
Content Type ◽  
Immunostimulatory Effect ◽  
Ifn Γ ◽  
Acquired Immune Responses

ABSTRACTInterleukin-18 (IL-18), which was originally called gamma interferon (IFN-γ)-inducing factor, has been shown to play an important role in innate and acquired immune responses. In this study, attenuatedErysipelothrix rhusiopathiaestrains were engineered to produce porcine IL-18 (poIL-18) and evaluated for their potential immunostimulatory effect in animals. Recombinant poIL-18 was successfully expressed in the recombinantE. rhusiopathiaestrains YS-1/IL-18 and KO/IL-18. The culture supernatant of YS-1/IL-18 was confirmed to induce IFN-γ production in murine splenocytesin vitro, and this production was inhibited by incubation with anti-poIL-18 monoclonal antibodies. Furthermore, more IFN-γ production was induced upon stimulation of splenocytes with concanavalin A for splenocytes from mice that were intraperitoneally inoculated with YS-1/IL-18 than for splenocytes from control mice inoculated with the parent strain YS-1. Peritoneal macrophages from mice preinoculated with YS-1/IL-18 exhibited enhanced phagocytosis ofSalmonella entericasubsp.entericaserovar Typhimurium compared with peritoneal macrophages from control mice preinoculated with YS-1. We also confirmed the immunostimulatory effect on humoral immune responses against antigens ofE. rhusiopathiaeandMycoplasma hyopneumoniaein gnotobiotic pigs that were orally preinoculated with KO/IL-18. Thus, these results provide evidence thatE. rhusiopathiaeis a promising vector for the expression of host cytokines and suggest the potential utility ofE. rhusiopathiaevector-encoded cytokines in the activation of host innate and acquired immune responses.

scholarly journals Immediate Interferon Gamma Induction Determines Murine Host Compatibility Differences between Toxoplasma gondii and Neospora caninum

2020 ◽  
Vol 88 (4) ◽  
Author(s):  
Rachel S. Coombs ◽  
Matthew L. Blank ◽  
Elizabeth D. English ◽  
Yaw Adomako-Ankomah ◽  
Ifeanyi-Chukwu Samuel Urama ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Interferon Gamma ◽  
Neospora Caninum ◽  
Ectopic Expression ◽  
Parasite Burden ◽  
Interleukin 12 ◽  
Content Type ◽  
Ifn Γ ◽  
And Control

ABSTRACT Rodents are critical for the transmission of Toxoplasma gondii to the definitive feline host via predation, and this relationship has been extensively studied as a model for immune responses to parasites. Neospora caninum is a closely related coccidian parasite of ruminants and canines but is not naturally transmitted by rodents. We compared mouse innate immune responses to N. caninum and T. gondii and found marked differences in cytokine levels and parasite growth kinetics during the first 24 h postinfection (hpi). N. caninum-infected mice produced significantly higher levels of interleukin-12 (IL-12) and interferon gamma (IFN-γ) by as early as 4 hpi, but the level of IFN-γ was significantly lower or undetectable in T. gondii-infected mice during the first 24 hpi. “Immediate” IFN-γ and IL-12p40 production was not detected in MyD88−/− mice. However, unlike IL-12p40−/− and IFN-γ−/− mice, MyD88−/− mice survived N. caninum infections at the dose used in this study. Serial measures of parasite burden showed that MyD88−/− mice were more susceptible to N. caninum infections than wild-type (WT) mice, and control of parasite burdens correlated with a pulse of serum IFN-γ at 3 to 4 days postinfection in the absence of detectable IL-12. Immediate IFN-γ was partially dependent on the T. gondii mouse profilin receptor Toll-like receptor 11 (TLR11), but the ectopic expression of N. caninum profilin in T. gondii had no impact on early IFN-γ production or parasite proliferation. Our data indicate that T. gondii is capable of evading host detection during the first hours after infection, while N. caninum is not, and this is likely due to the early MyD88-dependent recognition of ligands other than profilin.

scholarly journals The Life Cycle Stages of Pneumocystis murina Have Opposing Effects on the Immune Response to This Opportunistic Fungal Pathogen

2016 ◽  
Vol 84 (11) ◽  
pp. 3195-3205 ◽  
Author(s):  
Heather M. Evans ◽  
Grady L. Bryant ◽  
Beth A. Garvy
Keyword(s):  
Cell Wall ◽  
Life Cycle ◽  
Immune Responses ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Content Type ◽  
Life Cycle Stages ◽  
Ifn Γ

The cell wall β-glucans of Pneumocystis cysts have been shown to stimulate immune responses in lung epithelial cells, dendritic cells, and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with these innate immune cells. Here we report differences in the responses of both neonatal and adult mice to the trophic and cystic life cycle stages of Pneumocystis murina . The adult and neonatal immune responses to infection with Pneumocystis murina trophic forms were less robust than the responses to infection with a physiologically normal mixture of cysts and trophic forms. Cysts promoted the recruitment of nonresident innate immune cells and T and B cells into the lungs. Cysts, but not trophic forms, stimulated increased concentrations of the cytokine gamma interferon (IFN-γ) in the alveolar spaces and an increase in the percentage of CD4 + T cells that produce IFN-γ. In vitro , bone marrow-derived dendritic cells (BMDCs) stimulated with cysts produced the proinflammatory cytokines interleukin 1β (IL-1β) and IL-6. In contrast, trophic forms suppressed antigen presentation to CD4 + T cells, as well as the β-glucan-, lipoteichoic acid (LTA)-, and lipopolysaccharide (LPS)-induced production of interleukin 1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) by BMDCs. The negative effects of trophic forms were not due to ligation of mannose receptor. Our results indicate that optimal innate and adaptive immune responses to Pneumocystis species are dependent on stimulation with the cyst life cycle stage. Conversely, trophic forms suppress β-glucan-induced proinflammatory responses in vitro , suggesting that the trophic forms dampen cyst-induced inflammation in vivo .

scholarly journals Incubation of Whole Blood at 39°C Augments Gamma Interferon (IFN-γ)-Induced Protein 10 and IFN-γ Responses to Mycobacterium tuberculosis Antigens

2011 ◽  
Vol 18 (7) ◽  
pp. 1150-1156 ◽  
Author(s):  
Martine G. Aabye ◽  
Pernille Ravn ◽  
Isik S. Johansen ◽  
Jesper Eugen-Olsen ◽  
Morten Ruhwald
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Whole Blood ◽  
Incubation Temperature ◽  
Gamma Interferon ◽  
Content Type ◽  
Interleukin 7 ◽  
Ifn Γ

ABSTRACTA rarely challenged dogma in cell-mediated immune (CMI) assays is the incubation temperature, 37°C. Fever augments proinflammatory immune responsesin vivo, and the aim of this study was to explore whether incubation at fever-range temperature could increase antigen-specific biomarker responses. We compared CMI responses following incubation of whole blood at 37°C and 39°C. Whole blood was obtained from (i) 34 healthy subjects whose blood was incubated with TB10.4 antigen, present in theMycobacterium bovisbacillus Calmette-Guérin vaccine and many environmental mycobacteria; (ii) 8 TB patients and 8 controls incubated withMycobacterium tuberculosis-specific antigens in the QuantiFERON-TB Gold test (QFT-IT); and (iii) from both groups incubated with a T cell mitogen. T cell responses (gamma interferon [IFN-γ]) and responses from antigen-presenting cells (IFN-γ-induced protein 10 [IP-10]) were determined. We further evaluated the effect of adding interleukin-7 (IL-7) and blocking IL-10 during incubation. In TB patients, IFN-γ and IP-10 levels were increased 4.1- and 3.4-fold, respectively, at 39°C incubation (P< 0.001). Similar results were seen after mitogen stimulation. In subjects responding to TB10.4, the effects were less pronounced and significant only for IP-10. Incubation at 39°C increased IP-10 and IFN-γ responsiveness to both antigens and mitogen in persons with baseline or initial low responses. Adding IL-7 and blocking IL-10 augmented the effects in synergy with fever-range temperature. Incubation at fever-range temperature vividly increases CMI responsiveness to antigen stimulationin vitroin tuberculosis patients and may increase the sensitivity of CMI assays.

scholarly journals Impact of Malaria Preexposure on Antiparasite Cellular and Humoral Immune Responses after Controlled Human Malaria Infection

2015 ◽  
Vol 83 (5) ◽  
pp. 2185-2196 ◽  
Author(s):  
Joshua M. Obiero ◽  
Seif Shekalaghe ◽  
Cornelus C. Hermsen ◽  
Maxmillian Mpina ◽  
Else M. Bijker ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intradermal Injection ◽  
Content Type ◽  
Human Malaria ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Controlled Human Malaria Infection ◽  
Circulating Lymphocytes ◽  
Ifn Γ

To understand the effect of previous malaria exposure on antiparasite immune responses is important for developing successful immunization strategies. Controlled human malaria infections (CHMIs) using cryopreservedPlasmodium falciparumsporozoites provide a unique opportunity to study differences in acquisition or recall of antimalaria immune responses in individuals from different transmission settings and genetic backgrounds. In this study, we compared antiparasite humoral and cellular immune responses in two cohorts of malaria-naive Dutch volunteers and Tanzanians from an area of low malarial endemicity, who were subjected to the identical CHMI protocol by intradermal injection ofP. falciparumsporozoites. Samples from both trials were analyzed in parallel in a single center to ensure direct comparability of immunological outcomes. Within the Tanzanian cohort, we distinguished one group with moderate levels of preexisting antibodies to asexualP. falciparumlysate and another that, based onP. falciparumserology, resembled the malaria-naive Dutch cohort. PositiveP. falciparumserology at baseline was associated with a lower parasite density at first detection by quantitative PCR (qPCR) after CHMI than that for Tanzanian volunteers with negative serology. Post-CHMI, both Tanzanian groups showed a stronger increase in anti-P. falciparumantibody titers than Dutch volunteers, indicating similar levels of B-cell memory independent of serology. In contrast to the Dutch, Tanzanians failed to increaseP. falciparum-specificin vitrorecall gamma interferon (IFN-γ) production after CHMI, and innate IFN-γ responses were lower inP. falciparumlysate-seropositive individuals than in seronegative individuals. In conclusion, positiveP. falciparumlysate serology can be used to identify individuals with better parasite control but weaker IFN-γ responses in circulating lymphocytes, which may help to stratify volunteers in future CHMI trials in areas where malaria is endemic.

scholarly journals Analysis of Immune Responses against a Wide Range of Mycobacterium tuberculosis Antigens in Patients with Active Pulmonary Tuberculosis

2012 ◽  
Vol 19 (12) ◽  
pp. 1907-1915 ◽  
Author(s):  
Desta Kassa ◽  
Leonie Ran ◽  
Wudneh Geberemeskel ◽  
Mekashaw Tebeje ◽  
Amelewerk Alemu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Pulmonary Tuberculosis ◽  
Immune Responses ◽  
Expression Profiles ◽  
Enzyme Linked Immunosorbent Assay ◽  
Content Type ◽  
Active Pulmonary Tuberculosis ◽  
Tnf Α ◽  
Wide Range ◽  
Ifn Γ

ABSTRACTCharacterizing host immune responses to molecular targets ofMycobacterium tuberculosisis essential to develop effective immunodiagnostics and better vaccines. We investigated the immune response against a large series ofM. tuberculosisantigens, including 5 classical and 64 nonclassical (39 DosR regulon-encoded, 4 resuscitation-promoting factor [RPF], and 21 reactivation-associated) antigens in active-pulmonary-tuberculosis (TB) patients. Whole blood from TB patients (n= 34) was stimulatedin vitrowithM. tuberculosisantigens. Gamma interferon (IFN-γ) was measured after 7 days of stimulation, using an enzyme-linked immunosorbent assay (ELISA). The majority of the study participants responded to the classicalM. tuberculosisantigens TB10.4 (84.8%), early secreted antigenic target-6 kDa (ESAT-6)/CFP-10 (70.6%), and purified protein derivative (PPD) (55.9%). However, only 26.5% and 24.2% responded to HSP65 and Ag85A/B, respectively. Of the 64 nonclassical antigens, 23 (33.3%) were immunogenic (IFN-γ levels, >62 pg/ml) and 8 were strong inducers of IFN-γ (IFN-γ levels, ≥100 pg/ml). The RPF antigens were the most immunogenic. In addition, we observed distinct cytokine expression profiles in response to severalM. tuberculosisantigens by multiplex immunoassay. Tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), and IL-6 were commonly detected at high levels after stimulation with 4/15 latency antigens (Rv0081, Rv2006, Rv2629, and Rv1733c) and were found especially in supernatants of the three strong IFN-γ inducers (Rv2629, Rv1009, and Rv2389c). IL-8, IL-6, and IL-17 were exclusively detected after stimulation with Rv0574c, Rv2630, Rv1998, Rv054c, and Rv2028c. In conclusion, in active-pulmonary-TB patients, we identified 23 new immunogenicM. tuberculosisantigens. The distinct expression levels of IFN-γ, TNF-α, IL-6, and IL-10 in response to specific subsets ofM. tuberculosisantigens may be promising for the development of immunodiagnostics.

scholarly journals Interferon Gamma Reprograms Host Mitochondrial Metabolism through Inhibition of Complex II To Control Intracellular Bacterial Replication

2019 ◽  
Vol 88 (2) ◽  
Author(s):  
Forrest Jessop ◽  
Robert Buntyn ◽  
Benjamin Schwarz ◽  
Tara Wehrly ◽  
Dana Scott ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Mitochondrial Metabolism ◽  
Intracellular Bacteria ◽  
Content Type ◽  
Complex Ii ◽  
Key Factor ◽  
Ifn Γ ◽  
Bacterial Replication

ABSTRACT The mechanisms by which interferon gamma (IFN-γ) controls the replication of cytosolic pathogens independent of responses, such as the generation of reactive oxygen species/reactive nitrogen species (ROS/RNS), have not been fully elucidated. In the current study, we developed a model using Francisella tularensis, the causative agent of tularemia, in which pathways triggered by IFN-γ commonly associated with bacterial control were not required. Using this model, we demonstrated that IFN-γ-mediated production of itaconate and its ability to impair host mitochondrial function, independent of activity on the pathogen, were central for the restriction of bacterial replication in vitro and in vivo. We then demonstrate that IFN-γ-driven itaconate production was dispensable, as directly targeting complex II using cell membrane-permeable metabolites also controlled infection. Together, these findings show that while reprogramming of mitochondrial metabolism is a key factor in IFN-γ control of intracellular bacteria, the development of antimicrobial strategies based on targeting host mitochondrial metabolism independent of this cytokine may be an effective therapeutic approach.

scholarly journals Effect of Chemotherapy on Whole-Blood Cytokine Responses to Mycobacterium tuberculosis Antigens in a Small Cohort of Patients with Pulmonary Tuberculosis

2011 ◽  
Vol 18 (8) ◽  
pp. 1378-1386 ◽  
Author(s):  
Sylvie Bertholet ◽  
David J. Horne ◽  
Elsa M. Laughlin ◽  
Margery Savlov ◽  
Ines Tucakovic ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Whole Blood ◽  
Molecular Targets ◽  
Interleukin 10 ◽  
Content Type ◽  
Cytokine Responses ◽  
Small Cohort ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACTThe development of genomic and proteomic tools has enabled studies that begin to characterize the molecular targets of an effective host immune response toMycobacterium tuberculosis, including understanding the specific immune responses associated with tuberculosis (TB) disease progression, disease resolution, and the development of latency. One application of such tools is the development of diagnostic reagents and assays useful as a test of cure. Such a test could be of considerable importance for the evaluation of new therapeutics. We and others have previously described immunodominant proteins ofM. tuberculosis, including both vaccine and diagnostic candidates. In the present study, we describe the changes in immune responses to a panel of 71M. tuberculosisantigens in six patients during the course of therapy. The levels of six cytokines were measured in 24-h whole-blood assays with these antigens, revealing that gamma interferon (IFN-γ), tumor necrosis factor (TNF), and interleukin-10 (IL-10) were differentially regulated in response to a subset of antigens. Therefore, measuring the production of these three cytokines in response to a panel of carefully selectedM. tuberculosisproteins during the course of TB therapy might be a promising path toward the development of a test of cure and warrants further validation in larger cohorts of pulmonary TB patients.

scholarly journals INTERFERON GAMMA AND INTERLEUKIN-10 LEVELS IN PBMC OF ACTIVE AND LATENT TUBERCULOSIS PATIENTS AS WELL AS HEALTHY INDIVIDUALS

2018 ◽  
Vol 24 (2) ◽  
pp. 122
Author(s):  
I G.A. Wiradari Tedja ◽  
Jusak Nugraha1 ◽  
Betty Agustina Tambunan ◽  
Fransisca Sri Oetami
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Interleukin 10 ◽  
Healthy People ◽  
Pulmonary Tb ◽  
Latent Tb ◽  
Ifn Γ ◽  
The Mean ◽  
Fusion Antigen

Tuberculosis (TB), an infectious disease caused by a Mycobacterium tuberculosis, is still a health problem in Indonesia, and the world. One of the failures to control the TB epidemic is due to the lack of effective vaccines available today. Protective immune responses to M.tuberculosis are dominated by cellular immunity and less by humoral immunity. IFN-γ, and IL-10 play a role in the protection of against M.tuberculosis, and the pathogenesis of TB. Fusion antigen ESAT-6-CFP-10 has a strong antigenicity to T cells and stimulates specific cellular immune responses, thereby providing benefit in immune responses that are protective against M.tuberculosis infection. The aimed of this study was to know the difference betwen IFN-γ, and IL-10 levels on PBMC culture of active TB, latent TB, and healthy people after ESAT-6-CFP-10 fusion antigen stimulation. This study used an in vitro of quasi experimental design in PBMC cultures of active TB, latent TB, and healthy people groups stimulated by ESAT-6-CFP-10 antigen fusion Mycobacterium tuberculosis. IFN-γ, and IL-10 levels were measured by ELISA method. The results were analyzed by one-way ANOVA. The mean levels of IFN-γ post-stimulation of ESAT-6-CFP-10 fusion antigens did not differ (p=0.359) in the active pulmonary TB group (0.07 - 2114), latent TB (6.84 - 1381) and healthy people 1.88 - 1807.70), as well as the mean levels of IL-10 (p=0.712) in the active pulmonary TB (16.70 - 328.80), latent TB (29.70 - 323.60 ) and healthy people (31.30 - 958). There were no significant differences in levels of IFN-γ and IL-10 in active TB, latent TB, and healthy people after stimulation by fusion antigen ESAT-6-CFP-10. 

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