Unilateral necrotising toxoplasmic retinochoroiditis as the main clinical manifestation of a peptide transporter (TAP) deficiency.
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ABSTRACT:
SUBMITTER: Parissiadis A
PROVIDER: S-EPMC1772989 | biostudies-literature | 2005 Dec
REPOSITORIES: biostudies-literature
Publications
Unilateral necrotising toxoplasmic retinochoroiditis as the main clinical manifestation of a peptide transporter (TAP) deficiency.
Parissiadis A A Dormoy A A Fricker D D Hanau D D de la Salle H H Cazenave J-P JP Lenoble P P Donato L L
The British journal of ophthalmology 20051201 12
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Project description:Background/objectivesTo assess the ratio of scarred/active areas of fundus lesions in patients with presumed ocular toxoplasmosis.Subjects/methodsRetrospective monocentric study of patients with presumed ocular toxoplasmosis seen between May 2004 and February 2018. Patients with a positive anti-Toxoplasma serology presenting characteristic fundus lesions. Cases with images of both baseline active and scarred lesions of the fundus were included. The borders of each active or scarred lesion were delineated on colour photographs by two independent observers and the area of the lesions was calculated using Digimizer 4.2.2 (MedCalc Software, Ostend, Belgium). The interobserver variability of the measures was recorded and their means were used for further calculations. To study the ratio of the area of scarred retinochoroiditis over the area of the baseline active lesion (R).ResultsA total of 171 cases (83 males, 88 females) with a mean age of 31.6 ± 13.8 years were included. The average areas of active and scarred retinochoroiditis were, respectively, 1.32 ± 1.59 and 1.79 ± 2.36 optic disc area. The average ratio between scarred and active areas of retinochoroiditis was 1.36 [range 0.54-2.18]. The administration of a systemic treatment [R = 1.25, p = 0.003], the absence of a pre-existing scar [R = 1.05, p < 0.001] and a peripapillary location of the lesion [R = 0.85, p < 0.001] were each significantly associated with smaller scarred/active area ratios.ConclusionsWe assessed in a standardized manner the ratio of scarred/active areas of toxoplasmic lesions and showed that the area of scarred lesions was on average slightly larger than the area of active retinochoroiditis.
| S-EPMC8452670 | biostudies-literature
Project description:PurposeTo ascertain the clinical features and visual outcome of toxoplasma retinochoroiditis in a large series of cases.Subjects and methodsTwo hundred and thirty subjects diagnosed with active toxoplasma retinochoroiditis were prospectively followed for periods ranging from 269 to 1976 days. All patients presented with active retinochoroiditis and positive IgG T. gondii serology at the beginning of the study and received a standardized drug treatment for toxoplasmosis, both in the first episode and in the subsequent recurrences.ResultsThe group involved 118 (51.3%) men and 112 (48.7%) women, with ages ranging from 14 to 77 years, mean of 32.4 years (SD = 11.38). Primary retinochoroidal lesions were observed in 52 (22.6%) cases and active retinochoroiditis combined with old scars in 178 (77.4%) subjects at the beginning of the study. A hundred sixty-two recurrent episodes in 104 (45.2%) patients were observed during follow-up. New subclinical retinochoroidal lesions were detected in 23 of 162 (14.2%) recurrences episodes during the follow-up. Posterior segment complications were observed in 73 (31.7%) subjects. Retinochoroidal lesions adjacent to the optic nerve and in the macular area were observed in 27 of 40 (67.5%) cases of severe visual impairment (VA = 20/200 or worse).ConclusionToxoplasma retinochoroiditis in this population had a high recurrence rate after an active episode. Severe visual impairment was associated with location of the retinochoroidal scar, recurrences and posterior segment complications. It is crucial to consider the location of the lesion in studies analyzing visual prognosis as a measure for treatment effectiveness and prevention strategies.
| S-EPMC4852945 | biostudies-literature
Project description:ObjectiveTo define the swept-source optical coherence tomography (SS-OCT) features which distinguish ocular toxoplasmosis (OT) from other forms of retinochoroiditis.MethodsThis is a prospective diagnostic study enrolling 43 eyes of 43 patients with active toxoplasmic (TOXO) retinochoroiditis matched to 54 eyes (54 lesions) with non-TOXO retinochoroiditis evaluated by structural SS-OCT.ResultsThe finding of retinal hyper-reflective round deposits, sub-lesional choroidal thickening, and sub-lesional retinal pigment epithelium elevation were more likely to be found in TOXO lesions with a positive likelihood ratio of 45.2 (95% CI: 6.45-316.56), 23.86 (95% CI: 6.09-93.36), and 9.79 (95% CI: 4.22-22.7), respectively. The presence of each of these findings was associated with a high level for positive predictive value (PPV) (88.63-97.29), negative predictive value (NPV) (88.3-92.45), sensitivity (83.72-90.69), and specificity (90.74-98.14). Two-parameter model binary logistic regression suggested that sub-lesional retinal pigment epithelium elevation and sub-lesional choroidal thickening were significant predictors of the diagnosis of OT (Wald = 11.905, p < 0.001; Wald = 14.881, p < 0.001; respectively). By adding hyper-reflective round deposits along the posterior hyaloid or the retinal surface the model improved its performance with very good diagnostic accuracy with area under the curve (AUC) values of 0.96 (95% CI: 0.9-0.99) for two parameters model and 0.98 (95% CI: 0.93-0.99) for the three parameters model.ConclusionsOur results show that three OCT findings including retinal hyper-reflective round deposits, sub-lesional choroidal thickening, and sub-lesional retinal pigment epithelium elevation are more likely to occur in OT patients as compared with non-OT patients.
| S-EPMC9151801 | biostudies-literature
Project description:BackgroundsPCR is a proper technique that significantly improves toxoplasmosis diagnosis. However, a more sensitive technique is required. This study compared real-time PCR with nested PCR using B1, SAG-4, and MAG-1 bradyzoite genes to diagnose toxoplasmosis in toxoplasmic retinochoroiditis patients.MethodsBlood samples were collected from 10 patients with active toxoplasmic chorioretinal lesions and 10 healthy individuals. Blood samples including peripheral blood mononuclear cells (PBMCs), serum and whole blood samples were used for DNA extraction. Serum was also used to detect anti-toxoplasma IgG and IgM antibodies. Nested PCR and real-time PCR were performed using B1, SAG-4, and MAG-1 target genes.ResultsFive (50%) out of the 10 patients were tested positive for toxoplasmosis with nested PCR using the PBMC samples. All the five patients tested positive with nested PCR were also tested positive for toxoplasmosis with real-time PCR using the PBMC samples. The real-time PCR results demonstrated that 9(90%) out of the 10 patients were positive based on B1 and the remaining one (10%) was positive only based on MAG-1. In general, of the patients, five (50%) were positive using SAG-4 and three (30%) were positive in term of MAG-1 using PBMCs with real-time PCR.ConclusionIt appears that PBMC samples have the best performance as the PCR extraction method and are a good source for toxoplasmosis diagnosis. The use of B22 and B23 target genes due to their high sensitivity and specificity along with bradyzoite genes are recommended for toxoplasmosis diagnosis using PBMC samples with real-time PCR.
| S-EPMC8609853 | biostudies-literature
Project description:Toxoplasmic retinochoroiditis is a common, potentially blinding parasitic infection. We sought to define the spectrum and frequency of signs of active toxoplasmic retinochoroiditis by spectral domain optical coherence tomography (SD-OCT), and to identify clinical associations. Ninety eyes of 90 individuals presenting consecutively to a tertiary referral uveitis service with active toxoplasmic retinochoroiditis and gradable SD-OCT scans were evaluated prospectively. SD-OCT features were collated, and associations with lesion location, primary versus recurrent episode, serological status, human immunodeficiency virus infection and best-corrected Snellen visual acuity were explored. Active toxoplasmic retinochoroiditis presented with thickened (65%) and hyperreflective (61%) retina, choroidal thickening (55%) and hyporeflectivity (61%), hyperreflective vitreous dots (80%) and deposits (36%), and posterior hyaloid thickening (35%) on SD-OCT. Most signs occurred with similar frequency across clinical groups. Retinal hyporeflectivity (17%) was significantly associated with a visual acuity of 20/200 or worse at resolution. Our observations demonstrate that active toxoplasmic retinochoroiditis has diverse SD-OCT signs and that none are universally present. Retinal hyporeflectivity-suggesting liquefactive necrosis-predicts poor visual outcome.
| S-EPMC8782858 | biostudies-literature
Project description:Ocular toxoplasmosis is a major cause of posterior uveitis worldwide. The diagnosis is based mainly on ophthalmological examination. Biological diagnosis is necessary in atypical cases, and this requires aqueous humor sampling by anterior chamber paracentesis. We evaluated real-time PCR targeting the Toxoplasma gondii 529-bp repeat element, the Goldmann-Witmer coefficient (GWC), and immunoblotting for the diagnosis of toxoplasmic retinochoroiditis in 54 patients with atypical uveitis. The results of these biological tests, applied to paired aqueous humor-serum samples, were compared to the clinical findings. Combining either PCR or the GWC with immunoblotting increased the sensitivity to 73% or 70%, respectively. Together, PCR and the GWC had 80% sensitivity. If feasible, sensitivity can be increased by combining the three methods (85% sensitivity). The interval between symptom onset and anterior chamber paracentesis strongly influenced the detection of specific intraocular antibody synthesis. The sensitivity of the GWC increased from 45% to 56% when sampling was performed 10 days after symptom onset, and that of immunoblotting increased from 53% to 72% when puncture was performed 30 days after symptom onset. PCR analysis of aqueous humor samples detected toxoplasmic DNA in 55% of patients. In contrast to the results of immunoblotting and the GWC, the results of PCR were not influenced by the interval between symptom onset and paracentesis. PCR was more informative than the GWC and immunoblotting for immunocompromised patients. Acute necrotizing retinal lesions were significantly larger in PCR-positive patients, with a mean of 3.5 optic disc diameters, than in PCR-negative patients, with a mean of 1.5 optic disc diameters.
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Project description:Neoantigen burden is a major determinant of tumor immunogenicity, underscored by recent clinical experience with checkpoint blockade therapy. Yet the majority of patients do not express, or express too few, neoantigens, and hence are less responsive to immune therapy. Here we describe an approach whereby a common set of new antigens are induced in tumor cells in situ by transient downregulation of the transporter associated with antigen processing (TAP). Administration of TAP siRNA conjugated to a broad-range tumor-targeting nucleolin aptamer inhibited tumor growth in multiple tumor models without measurable toxicity, was comparatively effective to vaccination against prototypic mutation-generated neoantigens, potentiated the antitumor effect of PD-1 antibody or Flt3 ligand, and induced the presentation of a TAP-independent peptide in human tumor cells. Treatment with the chemically-synthesized nucleolin aptamer-TAP siRNA conjugate represents a broadly-applicable approach to increase the antigenicity of tumor lesions and thereby enhance the effectiveness of immune potentiating therapies.
| S-EPMC6704146 | biostudies-literature
Project description:Transporter associated with antigen processing (TAP), a key player in the major histocompatibility complex class I-restricted antigen presentation, makes an attractive target for viruses that aim to escape the immune system. Mechanisms of TAP inhibition vary among virus species. Bovine herpesvirus 1 (BoHV-1) is unique in its ability to target TAP for proteasomal degradation following conformational arrest by the UL49.5 gene product. The exact mechanism of TAP removal still requires elucidation. For this purpose, a TAP-GFP (green fluorescent protein) fusion protein is instrumental, yet GFP-tagging may affect UL49.5-induced degradation. Therefore, we constructed a series of TAP-GFP variants using various linkers to obtain an optimal cellular fluorescent TAP platform. Mel JuSo (MJS) cells with CRISPR/Cas9 TAP1 or TAP2 knockouts were reconstituted with TAP-GFP constructs. Our results point towards a critical role of GFP localization on fluorescent properties of the fusion proteins and, in concert with the type of a linker, on the susceptibility to virally-induced inhibition and degradation. The fluorescent TAP platform was also used to re-evaluate TAP stability in the presence of other known viral TAP inhibitors, among which only UL49.5 was able to reduce TAP levels. Finally, we provide evidence that BoHV-1 UL49.5-induced TAP removal is p97-dependent, which indicates its degradation via endoplasmic reticulum-associated degradation (ERAD).
| S-EPMC6952996 | biostudies-literature
Project description: Not available
| EMPIAR-11999 | biostudies-other
Project description: Not available
| EMPIAR-12009 | biostudies-other