Species specificity preliminary evaluation of an IL‐4‐based test for the differential diagnosis of human echinococcosis

Petrone, Linda; Albrich, Werner C.; Tamarozzi, Francesca; Frischknecht, Manuel; Gómez-Morales, María Ángeles; Teggi, Antonella; Hoffmann, Matthias; Goletti, Delia

doi:10.1111/pim.12695

Cited by 10 publications

(10 citation statements)

References 29 publications

(68 reference statements)

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“…Firstly, it supports the specificity of the immune response to viral-peptides in different clinical conditions; secondly, it suggests a possible application of the “IP-10 and Spike whole-blood test” as a potential additional tool for diagnostic and immune response evaluation of COVID-19-patients during the acute phase of the disease. These findings are in agreement with other cytokine release-based tests applied for the diagnosis of several infectious diseases [ 31 – 34 ]. Moreover, an additional possible application of this whole-blood based cytokine assay is the evaluation of immune response in SARS-CoV-2 vaccine trials.…”

Section: Discussionsupporting

confidence: 91%

Exploratory analysis to identify the best antigen and the best immune biomarkers to study SARS-CoV-2 infection

et al. 2021

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Background Recent studies proposed the whole-blood based IFN-γ-release assay to study the antigen-specific SARS-CoV-2 response. Since the early prediction of disease progression could help to assess the optimal treatment strategies, an integrated knowledge of T-cell and antibody response lays the foundation to develop biomarkers monitoring the COVID-19. Whole-blood-platform tests based on the immune response detection to SARS-CoV2 peptides is a new approach to discriminate COVID-19-patients from uninfected-individuals and to evaluate the immunogenicity of vaccine candidates, monitoring the immune response in vaccine trial and supporting the serological diagnostics results. Here, we aimed to identify in the whole-blood-platform the best immunogenic viral antigen and the best immune biomarker to identify COVID-19-patients. Methods Whole-blood was overnight-stimulated with SARS-CoV-2 peptide pools of nucleoprotein-(NP) Membrane-, ORF3a- and Spike-protein. We evaluated: IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL- 15, IL-17A, eotaxin, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF, RANTES, TNF-α, VEGF. By a sparse partial least squares discriminant analysis we identified the most important soluble factors discriminating COVID-19- from NO-COVID-19-individuals. Results We identified a COVID-19 signature based on six immune factors: IFN-γ, IP-10 and IL-2 induced by Spike; RANTES and IP-10 induced by NP and IL-2 induced by ORF3a. We demonstrated that the test based on IP-10 induced by Spike had the highest AUC (0.85, p < 0.0001) and that the clinical characteristics of the COVID-19-patients did not affect IP-10 production. Finally, we validated the use of IP-10 as biomarker for SARS-CoV2 infection in two additional COVID-19-patients cohorts. Conclusions We set-up a whole-blood assay identifying the best antigen to induce a T-cell response and the best biomarkers for SARS-CoV-2 infection evaluating patients with acute COVID-19 and recovered patients. We focused on IP-10, already described as a potential biomarker for other infectious disease such as tuberculosis and HCV. An additional application of this test is the evaluation of immune response in SARS-CoV-2 vaccine trials: the IP-10 detection may define the immunogenicity of a Spike-based vaccine, whereas the immune response to the virus may be evaluated detecting other soluble factors induced by other viral-antigens.

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Section: Discussionsupporting

confidence: 91%

Exploratory analysis to identify the best antigen and the best immune biomarkers to study SARS-CoV-2 infection

et al. 2021

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“…Therefore, this study offers hints for developing rapid T-cell-based assays for SARS-CoV-2 infection. Cytokine release-based tests are considered easy and valid tools several infectious diseases’ diagnosis ( (15) , (16) , (17) , (18) , (19) , (20) ). Moreover, whole-blood tests showed a good correlation with other experimental approaches involving peripheral blood mononuclear cell stimulation ( (28) , (29) , (30) ) which underlines their analytical robustness.…”

Section: Discussionmentioning

confidence: 99%

“…T-cell-based tests have been explored in several infectious diseases including viral infections ( (15) , (16) , (17) , (18) , (19) , (20) ) and cytokine-release-based tests in whole-blood are routinely or experimentally used for cytomegalovirus (CMV) infection monitoring ( 16 ), tuberculosis infection diagnosis ( 18 ) and have been explored for hepatitis B virus ( 15 ), toxoplasmosis ( 17 ) and cystic echinococcosis ( 19 , 20 ) diagnosis. This approach has not been scouted yet for SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

A whole blood test to measure SARS-CoV-2-specific response in COVID-19 patients

Petrone

Petruccioli

Vanini

et al. 2021

Clinical Microbiology and Infection

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Objectives To examine whether specific T-cell-responses to SARS-CoV-2 peptides can be detected in COVID-19 using a whole-blood experimental setting, which may be further explored as potential diagnostic tool. Methods We evaluated IFN-γ levels after stimulating whole-blood with spike and remainder-antigens peptides megapools (MP) derived from SARS-CoV-2 sequences; IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, eotaxin, basic FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF, RANTES, TNF-α, VEGF were also evaluated. Results IFN-γ-response to spike and remainder-antigens MPs was significantly increased in 35 COVID-19-patients compared to 29 “NO COVID-19”-individuals (medians spike-MP: 0.26 vs 0, p=0.0002; medians remainder-antigens-MP: 0.07 vs 0.02; p=0.02). This response was detected independently of patients’ clinical parameters. IFN-γ-response to SARS-CoV-2-unrelated antigens CMV and SEB was similar in COVID-19 compared to NO-COVID-19-invididuals (median CMV: 3.46 versus 5.28, p=0.16; median SEB: 12.68 versus 15.05; p=0.1). In response to spike-MPs in COVID-19- compared to “NO COVID-19”-individuals, we found significant higher median of IL-2 (50.08 vs 0, p=0.0018), IFN-γ (90.16 vs 0, p=0.01), IL-4 (0.52 vs 0, p=0.03), IL-13 (0.84 vs 0, p=0.007) and MCP-1 (4602 vs 359.2, p=0.05). Conclusions Immune response to SARS-CoV-2 peptides in a whole-blood assay is associated to COVID-19 and it is characterized by both Th1 and Th2 profile. This experimental approach may be useful for developing new T-cell based diagnostic tests for disease and vaccine settings.

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“…Five-hundred microliters of heparinized whole-blood in duplicate were stimulated with 1 μg/mL AgB-enriched fraction [20][21][22], 200 ng/mL staphylococcal enterotoxin B (SEB-stimulation control), or left unstimulated, and incubated overnight at 37˚C, 5% CO 2 . Supernatants were then harvested, frozen and sent to INMI for cytokine analysis.…”

Section: Whole-blood Testmentioning

confidence: 99%

“…Cytokine-release tests based on the stimulation of whole-blood in vitro are currently used for the diagnosis of latent tuberculosis [13][14][15] and have been explored in several infectious diseases such as hepatitis B [16], toxoplasmosis [17], cytomegalovirus infection [18], and COVID-19 [19]. An interleukin (IL)-4-release assay based on the in vitro stimulation of whole-blood with an enriched fraction of Antigen B (AgB) of E. granulosus or its peptides, has been set-up and preliminarily evaluated for CE diagnosis, showing potential to distinguish patients with active and inactive CE cysts [20][21][22]. Furthermore, several works described associations between cytokine profiles and CE clinical features [23][24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Accuracy of an experimental whole-blood test for detecting reactivation of echinococcal cysts

et al. 2021

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Background Cystic echinococcosis (CE) is a complex disease for which clear understanding of clinical manifestations is needed to avoid misdiagnosis, inappropriate treatment, and severe complications. We evaluated the accuracy of a whole-blood stimulation test based on Interleukin (IL)-4 detection in response to Antigen B (AgB) of Echinococcus granulosus sensu lato to discriminate cyst viability and detect cyst reactivation in patients with hepatic CE. Methodology/Principal findings Thirty patients with CE3b cysts and 37 patients with spontaneously-inactivated CE4-CE5 cysts were recruited (T0). After enrollment, 5 patients with CE3b cysts received albendazole, resulting in cyst solidification (CE4) in 4/5. Within a two-year follow-up, the whole-blood test was repeated at two time-points, in ≥14 (T1) and in ≥4 (T2) patients per group. IL-4 and a panel of other soluble factors were measured in the stimulated plasma. Baseline IL-4 levels were significantly higher in patients with CE3b compared to those with CE4 cysts (p = 0.006). Test accuracy for CE3b diagnosis had a sensitivity of 33–60% and a specificity of 76–95%, depending on the cut-off applied. Overall, IL-4 levels did not change significantly over time in either group; however, patients within the CE3b group showed a significant decrease of IL-1ra, IL-6, IL-8, G-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, FGF at T1 compared to T0 (p≤0.042). Conclusions/Significance Whole-blood IL-4-response to AgB is significantly higher in patients with active compared to inactive CE but apparently not modulated over time after treatment. On the contrary, the levels of IL-1ra, IL-6, IL-8, G-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, FGF significantly decreased in active CE during follow-up. Additional studies are needed to understand whether these findings might have a clinical significance for patients’ follow-up.

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Species specificity preliminary evaluation of an IL‐4‐based test for the differential diagnosis of human echinococcosis

Cited by 10 publications

References 29 publications

Exploratory analysis to identify the best antigen and the best immune biomarkers to study SARS-CoV-2 infection

Exploratory analysis to identify the best antigen and the best immune biomarkers to study SARS-CoV-2 infection

A whole blood test to measure SARS-CoV-2-specific response in COVID-19 patients

Accuracy of an experimental whole-blood test for detecting reactivation of echinococcal cysts

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