RESUMEN
Guillain-Barré syndrome (GBS) is a rare heterogenous disorder of the peripheral nervous system, which is usually triggered by a preceding infection, and causes a potentially life-threatening progressive muscle weakness1. Although GBS is considered an autoimmune disease, the mechanisms that underlie its distinct clinical subtypes remain largely unknown. Here, by combining in vitro T cell screening, single-cell RNA sequencing and T cell receptor (TCR) sequencing, we identify autoreactive memory CD4+ cells, that show a cytotoxic T helper 1 (TH1)-like phenotype, and rare CD8+ T cells that target myelin antigens of the peripheral nerves in patients with the demyelinating disease variant. We characterized more than 1,000 autoreactive single T cell clones, which revealed a polyclonal TCR repertoire, short CDR3ß lengths, preferential HLA-DR restrictions and recognition of immunodominant epitopes. We found that autoreactive TCRß clonotypes were expanded in the blood of the same patient at distinct disease stages and, notably, that they were shared in the blood and the cerebrospinal fluid across different patients with GBS, but not in control individuals. Finally, we identified myelin-reactive T cells in the nerve biopsy from one patient, which indicates that these cells contribute directly to disease pathophysiology. Collectively, our data provide clear evidence of autoreactive T cell immunity in a subset of patients with GBS, and open new perspectives in the field of inflammatory peripheral neuropathies, with potential impact for biomedical applications.
Asunto(s)
Autoinmunidad , Linfocitos T CD8-positivos , Síndrome de Guillain-Barré , Nervios Periféricos , Enfermedades del Sistema Nervioso Periférico , Células TH1 , Humanos , Biopsia , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Síndrome de Guillain-Barré/sangre , Síndrome de Guillain-Barré/líquido cefalorraquídeo , Síndrome de Guillain-Barré/etiología , Síndrome de Guillain-Barré/inmunología , Antígenos HLA-DR/inmunología , Epítopos Inmunodominantes/inmunología , Vaina de Mielina/inmunología , Nervios Periféricos/inmunología , Nervios Periféricos/patología , Enfermedades del Sistema Nervioso Periférico/complicaciones , Enfermedades del Sistema Nervioso Periférico/inmunología , Enfermedades del Sistema Nervioso Periférico/patología , Receptores de Antígenos de Linfocitos T/inmunología , Células TH1/inmunología , Células TH1/patología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/patología , Memoria InmunológicaRESUMEN
The aim of this study was to determine impact of lymph vascular space involvement (LVSI) on recurrence and survival in early stage of endometrial cancer. From 1991 through 2010, all endometrial cancer patients at University Hospital of Bari, Italy were identified. The Log-rank test and Kaplan-Meyer methods were used for time-to-event analysis to evaluate the effects of on lymph vascular space involvement recurrence rate and survival time. Of the 560 endometrial cancer patients, 525 underwent primary surgery. Of those, 399 had early stage disease. Three hundred and forty women were not found to have LVSI, whereas 59 were found to have lymph vascular space involvement. Forty-nine (12%) patients developed a recurrence and 20 of them showed lymph vascular space involvement. The statistical analysis demonstrated that LVSI was strongly associated with a poor survival (P < 0.0001). Lymph vascular space involvement is associated with a high risk of recurrence and poor overall survival in early stage of endometrial cancer; therefore, the clinical decision to decide whether or not a patient with early stage endometrial cancer should receive adjuvant therapy should be included the evaluation of lymph vascular space involvement.
Asunto(s)
Adenocarcinoma de Células Claras/patología , Vasos Sanguíneos/patología , Carcinoma Adenoescamoso/patología , Carcinoma Endometrioide/patología , Neoplasias Endometriales/patología , Vasos Linfáticos/patología , Recurrencia Local de Neoplasia , Neoplasias Quísticas, Mucinosas y Serosas/patología , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Adenoescamoso/mortalidad , Carcinoma Adenoescamoso/terapia , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/terapia , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/terapia , Femenino , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias Quísticas, Mucinosas y Serosas/mortalidad , Neoplasias Quísticas, Mucinosas y Serosas/terapia , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVE: To evaluate the presence of subfoveal hyperreflective dots (SfHD) using optical coherence tomography (OCT) in macular holes (MH) and establish whether there is a relationship with postoperative anatomical and functional outcomes. METHODS: An observational cross-sectional study was conducted at the Dr. Elías Santana Hospital. Sixty-eight eyes of 67 patients with a tomographic diagnosis of full-thickness MH who underwent pars plana vitrectomy (PPV) and internal limiting membrane (ILM) peeling were included. Preoperative and postoperative measurements were obtained using radial macular scans and HD raster scans with Optovue and Cirrus 5000 (Zeiss) OCT machines. The main outcome measures were anatomical closure by OCT and functional outcome through best-corrected visual acuity (BCVA). RESULTS: The anatomical closure rate in our study was 63%. MHs that failed to achieve anatomical closure exhibited a higher number of hyperreflective dots and worse postoperative BCVA. A statistically significant association was found between exposed retinal pigment epithelium (RPE) in microns and the number of SfHD (Pâ¯=â¯.001). CONCLUSION: SfHD is a common tomographic finding in MH, and the presence of a higher number of these points is associated with poorer anatomical and functional outcomes. This imaging finding is a potential prognostic biomarker in this pathology.
Asunto(s)
Perforaciones de la Retina , Tomografía de Coherencia Óptica , Agudeza Visual , Vitrectomía , Humanos , Perforaciones de la Retina/cirugía , Perforaciones de la Retina/diagnóstico por imagen , Estudios Transversales , Masculino , Femenino , Anciano , Pronóstico , Persona de Mediana Edad , Fóvea Central/diagnóstico por imagen , Fóvea Central/patología , Anciano de 80 o más Años , Biomarcadores , Epitelio Pigmentado de la Retina/patología , Epitelio Pigmentado de la Retina/diagnóstico por imagenRESUMEN
Multihost infectious disease outbreaks have endangered wildlife, causing extinction of frogs and endemic birds, and widespread declines of bats, corals, and abalone. Since 2013, a sea star wasting disease has affected >20 sea star species from Mexico to Alaska. The common, predatory sunflower star (Pycnopodia helianthoides), shown to be highly susceptible to sea star wasting disease, has been extirpated across most of its range. Diver surveys conducted in shallow nearshore waters (n = 10,956; 2006-2017) from California to Alaska and deep offshore (55 to 1280 m) trawl surveys from California to Washington (n = 8968; 2004-2016) reveal 80 to 100% declines across a ~3000-km range. Furthermore, timing of peak declines in nearshore waters coincided with anomalously warm sea surface temperatures. The rapid, widespread decline of this pivotal subtidal predator threatens its persistence and may have large ecosystem-level consequences.
Asunto(s)
Epidemias , Calor/efectos adversos , Rayos Infrarrojos/efectos adversos , Estrellas de Mar , Síndrome Debilitante/epidemiología , Síndrome Debilitante/etiología , Animales , Ecosistema , Explotaciones Pesqueras , Océanos y Mares/epidemiología , Océano Pacífico/epidemiología , Conducta Predatoria , Síndrome Debilitante/mortalidadRESUMEN
Innate immunity contributes to the pathogenesis of inflammatory bowel disease (IBD). However, the mechanisms of IBD mediated by innate immunity are incompletely understood and there are limited models of spontaneous innate immune colitis to address this question. Here we describe a new robust model of colitis occurring in the absence of adaptive immunity. RAG1-deficient mice expressing TNFAIP3 in intestinal epithelial cells (TRAG mice) spontaneously developed 100% penetrant, early-onset colitis that was limited to the colon and dependent on intestinal microbes but was not transmissible to co-housed littermates. TRAG colitis was associated with increased mucosal numbers of innate lymphoid cells (ILCs) and depletion of ILC prevented colitis in TRAG mice. ILC depletion also therapeutically reversed established colitis in TRAG mice. The colitis in TRAG mice was not prevented by interbreeding to mice lacking group 3 ILC nor by depletion of TNF. Treatment with the JAK inhibitor ruxolitinib ameliorated colitis in TRAG mice. This new model of colitis, with its predictable onset and colon-specific inflammation, will have direct utility in developing a more complete understanding of innate immune mechanisms that can contribute to colitis and in pre-clinical studies for effects of therapeutic agents on innate immune-mediated IBD.