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1.
Clin Immunol ; 247: 109219, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36581221

RESUMO

BACKGROUND: HLA-A29-positive birdshot chorioretinitis (BCR) is an inflammatory eye disorder that is generally assumed to be caused by an autoimmune response to HLA-A29-presented peptides from retinal arrestin (SAG), yet the epitopes recognized by CD8+ T cells from patients remain to be identified. OBJECTIVES: The identification of natural ligands of SAG presented by HLA-A29. To quantify CD8+ T cells reactive to antigenic SAG peptides presented by HLA-A29 in patients and controls. METHODS: We performed mass-spectrometry based immunopeptidomics of HLA-A29 of antigen-presenting cell lines from patients engineered to express SAG. MHC-I Dextramer technology was utilised to determine expansion of antigen-specific CD8+ T cells reactive to SAG peptides in complex with HLA-A29 in a cohort of BCR patients, HLA-A29-positive controls, and HLA-A29-negative controls. RESULTS: We report on the naturally presented antigenic SAG peptides identified by sequencing the HLA-A29 immunopeptidome of antigen-presenting cells of patients. We show that the N-terminally extended SAG peptide precursors can be trimmed in vitro by the antigen-processing aminopeptidases ERAP1 and ERAP2. Unexpectedly, no enhanced antigen engagement by CD8+ T cells upon stimulation with SAG peptides was observed in patients or HLA-A29-positive controls. Multiplexed HLA-A29-peptide dextramer profiling of a case-control cohort revealed that CD8+ T cells specific for these SAG peptides were neither detectable in peripheral blood nor in eye biopsies of patients. CONCLUSIONS: Collectively, these findings demonstrate that SAG is not a CD8+ T cell autoantigen and sharply contrast the paradigm in the pathogenesis of BCR. Therefore, the mechanism by which HLA-A29 is associated with BCR does not involve SAG.


Assuntos
Coriorretinite , Humanos , Coriorretinopatia de Birdshot , Arrestina , Antígenos HLA-A , Retina , Linfócitos T CD8-Positivos , Peptídeos/metabolismo , Autoantígenos , Aminopeptidases , Antígenos de Histocompatibilidade Menor
2.
Sci Rep ; 7: 41595, 2017 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-28128370

RESUMO

Retinal diseases generally are vision-threatening conditions that warrant appropriate clinical decision-making which currently solely dependents upon extensive clinical screening by specialized ophthalmologists. In the era where molecular assessment has improved dramatically, we aimed at the identification of biomarkers in 175 ocular fluids to classify four archetypical ocular conditions affecting the retina (age-related macular degeneration, idiopathic non-infectious uveitis, primary vitreoretinal lymphoma, and rhegmatogenous retinal detachment) with one single test. Unsupervised clustering of ocular proteins revealed a classification strikingly similar to the clinical phenotypes of each disease group studied. We developed and independently validated a parsimonious model based merely on three proteins; interleukin (IL)-10, IL-21, and angiotensin converting enzyme (ACE) that could correctly classify patients with an overall accuracy, sensitivity and specificity of respectively, 86.7%, 79.4% and 92.5%. Here, we provide proof-of-concept for molecular profiling as a diagnostic aid for ophthalmologists in the care for patients with retinal conditions.


Assuntos
Proteínas do Olho/metabolismo , Doenças Retinianas/diagnóstico , Doenças Retinianas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Humor Aquoso/metabolismo , Biomarcadores , Tomada de Decisão Clínica , Análise por Conglomerados , Biologia Computacional/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteoma , Proteômica/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
3.
Ned Tijdschr Geneeskd ; 160: D203, 2016.
Artigo em Holandês | MEDLINE | ID: mdl-27507411

RESUMO

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare, autosomal recessive inheritable disorder characterized by progressive elastic fibre calcification. CASE DESCRIPTION: Here we describe two patients with different presentations of PXE. Patient A, an 11-year-old girl, visited the dermatologist because of yellow papules (pseudoxanthomas) on the side of her neck. With the aid of a skin biopsy, the dermatologist diagnosed PXE. Some years later, patient A developed symptoms of intermittent claudication due to arterial calcifications. Supervised exercise training diminished these symptoms. Patient B, a 55-year-old man, visited the ophthalmologist due to recent onset of metamorphopsia. The ophthalmologist discovered a subretinal haemorrhage and observed changes in the retina consistent with PXE. Severe loss of vision was prevented by intraocular anti-VEGF injections. Upon further investigation, pseudoxanthomas and arterial calcifications were found. CONCLUSION: PXE is a rare monogenetic disorder with dermatological, ocular and vascular manifestations. With these two case reports we have illustrated how the initial clinical presentation and symptomatology may vary widely.


Assuntos
Pseudoxantoma Elástico/complicações , Pseudoxantoma Elástico/diagnóstico , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
4.
Ocul Immunol Inflamm ; 24(1): 77-80, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-24945498

RESUMO

PURPOSE: Previous studies have suggested a link between Q fever and uveitis. We determined whether Coxiella burnetii causes intraocular infection in C. burnetii-seropositive patients with idiopathic uveitis. METHODS: From a retrospective observational case series, paired aqueous humor and serum samples from 10 C. burnetii-seropositive patients with idiopathic uveitis were examined for intraocular antibody production by using the Goldmann-Witmer coefficient and by polymerase chain reaction (PCR). RESULTS: Although intraocular IgG against C. burnetii was detected, no intraocular antibody production was observed (low Goldmann Wittmer coefficients). All PCR results were negative. CONCLUSIONS: Uveitis due to an intraocular infection with C. burnetii is unlikely.


Assuntos
Anticorpos Antibacterianos/sangue , Humor Aquoso/imunologia , Coxiella burnetii/imunologia , Infecções Oculares Bacterianas/microbiologia , Febre Q/microbiologia , Uveíte/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humor Aquoso/microbiologia , Coxiella burnetii/genética , DNA Bacteriano/genética , Ensaio de Imunoadsorção Enzimática , Infecções Oculares Bacterianas/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Febre Q/imunologia , Estudos Retrospectivos , Uveíte/imunologia , Adulto Jovem
5.
J Biomed Opt ; 7(2): 190-8, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11966303

RESUMO

To quantify dye leakage in ocular fluorescein angiography, the arterial concentration of sodium fluorescein has to be determined. We investigated whether the nonlinear relationship between the fluorescein concentration and the fluorescence intensity obtained by in vitro measurements corresponds with that measured in vivo in a retinal artery. The time series of fluorescence in a retinal artery were recorded using an in-house-designed and -built confocal scanning laser ophthalmoscope in 11 healthy volunteers. Three different doses of sodium fluorescein were injected successively. About 10 min after the last injection a venous blood sample was drawn. The three in vivo peak intensities were fitted by least squares on the in vitro calibration curve using the first peak concentration and an intensity scaling factor as the two unknown parameters. The fit showed that the saturation of the three in vivo peak intensities corresponded well with the in vitro data. Calculation of the intensity scaling factor from the blood sampling data confirmed the result of the fit. The fitted concentration was verified by showing that the cardiac output necessary to obtain this concentration was within the physiological range. The fluorescence measured in our in vitro experimental setup corresponded well with the in vivo measurements. Therefore, the results from in vitro measurements can be applied in the analysis of fluorescein angiograms.


Assuntos
Angiofluoresceinografia/instrumentação , Fluoresceína , Corantes Fluorescentes , Doenças Retinianas/diagnóstico , Adulto , Desenho de Equipamento , Feminino , Humanos , Técnicas In Vitro , Masculino , Óptica e Fotônica/instrumentação
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