Craniocerebral involvement in lymphoma

Nine-hundred-eighty-nine patients with lymphoma were studied. Fifty-three cases (5.3%) had lymphomatous craniocerebral infiltration. The principal factors of risk for this complication were: advanced stage of the lymphoma (III or IV), diffuse histiocytic, diffuse poorly differentiated lymphocytic, or mixed cellularity lymphoma histological type, bone marrow involvement, and previous systemic chemotherapy. Thirty-two per cent of the cases of meningeal lymphomatous infiltration were asymptomatic and represented autopsy findings. CT-scan was an useful test to detect brain focal parenchymatous infiltration, as opposed to meningeal infiltration. Mean survival time in patients with lymphomatous meningeal infiltration was 4.3 months, following the combined use of systemic chemotherapy, radiation therapy and intrathecal methotrexate. Two cases had primary cerebral lymphoma, although without associated immunodeficiency Twenty patients (2%) had intracranial hemorrhage, in clear relationship with platelet alterations. Fifteen patients (1.5%) had CNS infection, caused by common bacteriae or opportunistic agents. In 7 cases, the diagnosis was made at autopsy. Thirty-six autopsies were performed. In 8 cases (22%), pathologic findings such as, demyelination, microcalcificat ons, coagulative necrosis, or gliosis, suggested complications from treatment

The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity

Host responses against metazoan parasites or an array of environmental substances elicit type 2 immunity. Despite its protective function, type 2 immunity also drives allergic diseases. The mechanisms that regulate the magnitude of the type 2 response remain largely unknown. Here, we show that genetic ablation of a receptor tyrosine kinase encoded byTyro3in mice or the functional neutralization of its ortholog in human dendritic cells resulted in enhanced type 2 immunity. Furthermore, the TYRO3 agonist PROS1 was induced in T cells by the quintessential type 2 cytokine, interleukin-4. T cell-specificPros1knockouts phenocopied the loss ofTyro3 Thus, a PROS1-mediated feedback from adaptive immunity engages a rheostat, TYRO3, on innate immune cells to limit the intensity of type 2 responses.Fil: Chan, Pamela Y.. University of Yale. School of Medicine; Estados UnidosFil: Carrera Silva, Eugenio Antonio. University of Yale. School of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: De Kouchkovsky, Dimitri. University of Yale. School of Medicine; Estados UnidosFil: Joannas, Leonel D.. University of Yale. School of Medicine; Estados UnidosFil: Hao, Liming. University of Yale. School of Medicine; Estados UnidosFil: Hu, Donglei. University of California; Estados UnidosFil: Huntsman, Scott. University of California; Estados UnidosFil: Eng, Celeste. University of California; Estados UnidosFil: Licona Limón, Paula. University of Yale. School of Medicine; Estados UnidosFil: Weinstein, Jason S.. University of Yale. School of Medicine; Estados UnidosFil: De Broski, Herbert R.. University of California; Estados UnidosFil: Craft , Joseph E.. University of Yale. School of Medicine; Estados UnidosFil: Flavell, Richard A.. University of Yale. School of Medicine; Estados UnidosFil: Repetto, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Correale, Jorge. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas ; ArgentinaFil: Burchard, Esteban G.. University of California; Estados UnidosFil: Torgerson, Dora G.. University of California; Estados UnidosFil: Ghosh, Sourav. University of Yale. School of Medicine; Estados UnidosFil: Rothlin, Carla V.. University of Yale. School of Medicine; Estados Unido

Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers

Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death.

Regulated glycosylation controls T cell processes, including activation, differentiation and homing by creating or masking ligands for endogenous lectins. Here we show that stimuli promoting T helper type 1 (TH1), TH2 or interleukin 17-producing T helper (TH-17) differentiation can differentially regulate the glycosylation pattern of T helper cells and modulate their susceptibility to galectin-1, a glycan-binding protein with anti-inflammatory activity. Although TH1- and TH-17-differentiated cells expressed the repertoire of cell surface glycans critical for galectin-1-induced cell death, TH2 cells were protected from galectin-1 through differential sialylation of cell surface glycoproteins. Consistent with those findings, galectin-1-deficient mice developed greater TH1 and TH-17 responses and enhanced susceptibility to autoimmune neuroinflammation. Our findings identify a molecular link among differential glycosylation of T helper cells, susceptibility to cell death and termination of the inflammatory response