Stimulated Immune Response by TruCulture® Whole Blood Assay in Patients With European Lyme Neuroborreliosis: A Prospective Cohort Study

Ørbæk, Mathilde; Gynthersen, Rosa Maja Møhring; Mens, Helene; Stenör, Christian; Wiese, Lothar; Brandt, Christian; Ostrowski, Sisse Rye; Nielsen, Susanne Dam; Lebech, Anne‐Mette

doi:10.3389/fcimb.2021.666037

Cited by 8 publications

(11 citation statements)

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“…A validation study for other cellular tests for LB based on IFN-g production among others is currently ongoing (96). Intriguingly, a recent study showed that stimulation of whole blood of 22 Lyme neuroborreliosis patients provided lower IL-12 and IFN-g concentrations compared to healthy controls, which indicates a limited Th1 response (97). Although these authors did not stimulate with B. burgdorferi in their whole blood assay, they stimulated with various pathogens to study a broad function of different signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Borrelia burgdorferi Is a Poor Inducer of Gamma Interferon: Amplification Induced by Interleukin-12

et al. 2022

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Background Laboratory diagnosis of Lyme borreliosis (LB) is mainly based on serology, which has limitations, particularly in the early stages of the disease. In recent years there have been conflicting reports concerning a new diagnostic tool using the cytokine interferon-gamma (IFN-γ). Previous studies have generally found low concentrations of IFN-γ in early LB infection. The goal of this study is to investigate IFN-γ regulation during early LB and provide insights into the host response to B. burgdorferi . Methods We performed in vitro experiments with whole blood assays and peripheral blood mononuclear cells (PBMCs) of LB patients and healthy volunteers exposed to B. burgdorferi and evaluated the IFN-γ response using ELISA and related interindividual variation in IFN-γ production to the presence of single nucleotide polymorphisms. Results IFN-γ production of B. burgdorferi - exposed PBMCs and whole blood was amplified by the addition of IL-12 to the stimulation system. This effect was observed after 24 hours of B. burgdorferi stimulation in both healthy individuals and LB patients. The effect was highly variable between individuals, but was significantly higher in LB patients six weeks since the start of antibiotic treatment compared to healthy individuals. IL-12 p40 and IL-18 mRNA was upregulated upon exposure to B. burgdorferi , whereas IL-12 p35 and IFN-γ mRNA expression remained relatively unchanged. SNP Rs280520 in the downstream IL-12 pathway, Tyrosine Kinase 2, was associated with increased IFN-γ production. Conclusions This study shows that IL-12 evokes an IFN-γ response in B. burgdorferi exposed cells, and LB patients and healthy controls respond differently to this stimulation.

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Section: Discussionmentioning

confidence: 99%

Borrelia burgdorferi Is a Poor Inducer of Gamma Interferon: Amplification Induced by Interleukin-12

et al. 2022

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“…Recent studies applying TruCulture ® have characterized immune function by this assay in association with e.g. Type 1 diabetes ( 23 ), schizophrenia ( 24 ), tuberculosis ( 25 ), pancreaticoduodenectomy ( 26 ), hematopoietic stem cell transplantation ( 27 ), neuroborreliosis ( 28 ), psoriasis ( 29 ) and in healthy individuals ( 18 , 20 , 21 , 23 – 26 ).…”

Section: Introductionmentioning

confidence: 99%

Innate immune function during antineoplastic treatment is associated with 12-months survival in non-small cell lung cancer

et al. 2022

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IntroductionThe immune system has proven to be a key player in the progression as well as containment of cancer with new treatment strategies based on immunotherapy targeting this interaction. Assessing immune function could reveal critical information about the immune response to therapeutic interventions, revealing predictive biomarkers for tailored care and precision medicine.MethodsWe investigated immune function in 37 patients with inoperable non-small cell lung cancer (NSCLC) undergoing treatment with PD-L1 immune checkpoint inhibitor (ICI), chemotherapy (CT) or chemo-radiotherapy (CT/RT). Blood samples before (day 0) and during therapy (day 7, 21 and 80) were investigated by a standardized immunoassay, TruCulture®.ResultsOutcomes revealed a developing innate immune response induced by both immunotherapy and chemotherapy. NSCLC-patients displayed evidence of chronic innate immune activation and exhaustion prior to treatment. This pattern was particularly pronounced during treatment in patients dying within 12-months follow-up. Compared to treatment with CT, ICI demonstrated a higher ex vivo-stimulated release of proinflammatory cytokines.DiscussionThese preliminary findings may pave the way for tailored treatment and immune-monitoring.

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“…One study found that TruCulture ® was able to discriminate between active and latent tuberculosis by investigating stimulated IFN-g responses (19). The TruCulture ® assay has also been used in several clinical studies at our center (13)(14)(15)(16).…”

Section: Discussionmentioning

confidence: 99%

“…The method of TruCulture ® sampling has been reported in previous studies (13)(14)(15)(16). In brief, peripheral blood was collected in lithium heparin anticoagulated whole blood tubes and transferred into the four prewarmed TruCulture ® tubes after 60 minutes (+/-15 min).…”

Section: Truculture ®mentioning

confidence: 99%

The Induced Immune Response in Patients With Infectious Spondylodiscitis: A Prospective Observational Cohort Study

et al. 2022

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IntroductionInfectious spondylodiscitis is a rare infection of the intervertebral disc and the adjacent vertebral bodies that often disseminates and requires long-term antibiotic therapy. Immunologic profiling of patients with infectious spondylodiscitis could allow for a personalized medicine strategy. We aimed to examine the induced immune response in patients with infectious spondylodiscitis during and after antibiotic therapy. Furthermore, we explored potential differences in the induced immune response depending on the causative pathogen and the dissemination of the disease.MethodsThis was a prospective observational cohort study that enrolled patients with infectious spondylodiscitis between February 2018 and August 2020. A blood sample was collected at baseline, after four to six weeks of antibiotic therapy (during antibiotic therapy), and three to seven months after end of antibiotic therapy (post-infection). The induced immune response was assessed using the standardized functional immune assay TruCulture®. We used a panel of three immune cell stimuli (lipopolysaccharide, Resiquimod and polyinosinic:polycytodylic acid) and an unstimulated control. For each stimulus, the induced immune response was assessed by measuring the released concentration of Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, Interferon-γ (IFN-γ) and Tumor necrosis factor-α (TNF-α) in pg/mL.ResultsIn total, 49 patients with infectious spondylodiscitis were included. The induced immune responses were generally lower than references at baseline, but the cytokine release increased in patients after treatment with antibiotic therapy. Post-infection, most of the released cytokine concentrations were within the reference range. No significant differences in the induced immune responses based on stratification according to the causative pathogen or dissemination of disease were found.ConclusionWe found lower induced immune responses in patients with infectious spondylodiscitis at baseline. However, post-infection, the immune function normalized, indicating that an underlying immune deficiency is not a prominent factor for spondylodiscitis. We did not find evidence to support the use of induced immune responses as a tool for prediction of the causative pathogen or disease dissemination, and other methods should be explored to guide optimal treatment of patients with infectious spondylodiscitis.

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Stimulated Immune Response by TruCulture® Whole Blood Assay in Patients With European Lyme Neuroborreliosis: A Prospective Cohort Study

Cited by 8 publications

References 40 publications

Borrelia burgdorferi Is a Poor Inducer of Gamma Interferon: Amplification Induced by Interleukin-12

Borrelia burgdorferi Is a Poor Inducer of Gamma Interferon: Amplification Induced by Interleukin-12

Innate immune function during antineoplastic treatment is associated with 12-months survival in non-small cell lung cancer

The Induced Immune Response in Patients With Infectious Spondylodiscitis: A Prospective Observational Cohort Study

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