T‐cell profiles elicited by <i>Toxoplasma gondii</i> in acutely/chronically infected humans

Silva-Gutiérrez, Nubia; Zaky, Rima Bahsas; Bouchard, Morella; Angel, G.; Amoroso, Antonio; Salmen, Siham

doi:10.1111/pim.12532

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…SAG1 is highly immunogenic, which may lead to its degradation by phagocytes, in contrast to GRA family proteins, which are associated with TGF-ß production and dampening of the immune response. 34,35 It is also possible that SAG1 is not shed by tachyzoites because it is surface protein, unlike GRA1, which is a secretory protein. A secretory protein may be released in higher amounts from the parasite, while a structural protein could be made only in sufficient quantity for assembly of the parasite surface or remain localized there rather than released into systemic circulation.…”

Section: Discussionmentioning

confidence: 99%

Detection of Toxoplasmic Encephalitis in HIV Positive Patients in Urine with Hydrogel Nanoparticles

Steinberg

Bowman²,

Diestra

et al. 2020

Preprint

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Diagnosis of toxoplasmic encephalitis (TE) is challenging under the best clinical circumstances. The poor sensitivity of quantitative polymerase chain reaction (qPCR) for Toxoplasma in blood and CSF and the limited availability of molecular diagnostics and imaging technology leaves clinicians in resource-limited settings with few options other than empiric treatment. Here we describe proof of concept for a novel urine diagnostics for TE using Poly-N-isoproplyacrylamide nanoparticles dyed with Reactive Blue-221 to concentrate antigens, substantially increasing the limit of detection. After nanoparticle-concentration, a standard western blotting technique with a monoclonal antibody was used for antigen detection. Limit of detection was 7.8pg/ml and 31.3pg/ml of T. gondii antigens GRA1 and SAG1, respectively. To characterize this diagnostic approach, 164 hospitalized HIV-infected patients with neurological symptoms compatible with TE were tested for 1) T. gondii serology (121/147, positive samples/total samples tested), 2) qPCR in cerebrospinal fluid (11/41), 3) qPCR in blood (10/112), and 4) urinary GRA1 (30/164) and SAG1 (12/164). GRA1 appears to be superior to SAG1 for detection of TE antigens in urine. Fifty-one HIV-infected, T. gondii seropositive but asymptomatic persons all tested negative by nanoparticle western blot and blood qPCR, suggesting the test has good specificity for TE for both GRA1 and SAG1. In a subgroup of 44 patients, urine samples were assayed with mass spectrometry parallel-reaction-monitoring (PRM) for the presence of T. gondii antigens. PRM identified antigens in 8 samples, 6 of which were concordant with the urine diagnostic. Our results demonstrate nanoparticle technology potential for a noninvasive diagnostic test for TE. Moving forward, GRA1 is a promising target for antigen based diagnostics for TE.

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Section: Discussionmentioning

confidence: 99%

Detection of Toxoplasmic Encephalitis in HIV Positive Patients in Urine with Hydrogel Nanoparticles

Steinberg

Bowman²,

Diestra

et al. 2020

Preprint

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“…Our study did show that GRA1 performed significantly better than SAG1 to detect Toxoplasma antigen in urine. SAG1 has previously been shown to be a useful target for IgG T. gondii antibody serology with both high sensitivity and specificity; however, many groups have failed to develop an assay that consistently detects active T. gondii infections (such as TE) using SAG1 antigen [20,[33][34][35][36]. Our assay's poor positive percent agreement for SAG1 may indicate that the antigen is excreted at low abundance or too degraded in the urine for consistent immunoassay detection.…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 98%

Detection of toxoplasmic encephalitis in HIV positive patients in urine with hydrogel nanoparticles

et al. 2021

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Background Diagnosis of toxoplasmic encephalitis (TE) is challenging under the best clinical circumstances. The poor clinical sensitivity of quantitative polymerase chain reaction (qPCR) for Toxoplasma in blood and CSF and the limited availability of molecular diagnostics and imaging technology leaves clinicians in resource-limited settings with few options other than empiric treatment. Methology/principle findings Here we describe proof of concept for a novel urine diagnostics for TE using Poly-N-isoproplyacrylamide nanoparticles dyed with Reactive Blue-221 to concentrate antigens, substantially increasing the limit of detection. After nanoparticle-concentration, a standard western blotting technique with a monoclonal antibody was used for antigen detection. Limit of detection was 7.8pg/ml and 31.3pg/ml of T. gondii antigens GRA1 and SAG1, respectively. To characterize this diagnostic approach, 164 hospitalized HIV-infected patients with neurological symptoms compatible with TE were tested for 1) T. gondii serology (121/147, positive samples/total samples tested), 2) qPCR in cerebrospinal fluid (11/41), 3) qPCR in blood (10/112), and 4) urinary GRA1 (30/164) and SAG1 (12/164). GRA1 appears to be superior to SAG1 for detection of TE antigens in urine. Fifty-one HIV-infected, T. gondii seropositive but asymptomatic persons all tested negative by nanoparticle western blot and blood qPCR, suggesting the test has good specificity for TE for both GRA1 and SAG1. In a subgroup of 44 patients, urine samples were assayed with mass spectrometry parallel-reaction-monitoring (PRM) for the presence of T. gondii antigens. PRM identified antigens in 8 samples, 6 of which were concordant with the urine diagnostic. Conclusion/significances Our results demonstrate nanoparticle technology’s potential for a noninvasive diagnostic test for TE. Moving forward, GRA1 is a promising target for antigen based diagnostics for TE.

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“…Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that causes infections in warm blooded animals including humans [1]. Infections with T. gondii in man are commonly asymptomatic or cause mild symptoms that are self-limited [2].…”

Section: Introductionmentioning

confidence: 99%

Toxoplasma gondii infection and a history of surgery: A case control seroprevalence study

Alvarado‐Esquivel

Sánchez‐Anguiano

Hernández‐Tinoco

et al. 2018

EuJMI

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We determined the association between having a history of surgery and the seroreactivity to T. gondii. An age- and gender-matched case-control study of 391 subjects with a history of surgery and 391 subjects without this history was performed. Sera of subjects were analyzed for detection of anti-T. gondii immunoglobulin G (IgG) and M (IgM) antibodies using enzyme-linked immunoassays. Anti-T. gondii IgG antibodies were found in 25 (6.4%) of the 391 cases and in 21 (5.4%) of the 391 controls (odds ratio [OR] = 1.29; 95% confidence interval [CI]: 0.66–2.18; P = 0.54). The frequency of cases with high IgG antibody levels (10/25: 40.0%) was equal to that found in controls (8/21: 38.1%) (OR = 1.08; 95% CI: 0.32–3.56; P = 0.89). Of the 25 anti-T. gondii IgG antibody seropositive cases, 5 (16.0%) were also positive for anti-T. gondii IgM antibodies. Meanwhile, of the 21 anti-T. gondii IgG antibody seropositive controls, 4 (19.0%) were also positive for anti-T gondii IgM antibodies (OR = 0.81; 95% CI: 0.17–3.72; P = 0.80). Logistic regression showed that only the variable "hysterectomy" was associated with T. gondii seropositivity (OR = 4.6; 95% CI: 1.6–13.4; P = 0.005). Results suggest that having a history of surgery is not an important risk factor for infection with T. gondii. However, the link between T. gondii infection and hysterectomy should be further investigated.

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T‐cell profiles elicited by Toxoplasma gondii in acutely/chronically infected humans

Cited by 7 publications

References 27 publications

Detection of Toxoplasmic Encephalitis in HIV Positive Patients in Urine with Hydrogel Nanoparticles

Detection of Toxoplasmic Encephalitis in HIV Positive Patients in Urine with Hydrogel Nanoparticles

Detection of toxoplasmic encephalitis in HIV positive patients in urine with hydrogel nanoparticles

Toxoplasma gondii infection and a history of surgery: A case control seroprevalence study

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