Funciones ejecutivas y bienestar subjetivo en alumnos que presentan trastorno del espectro autista e inteligencia sobre el rango promedio

Students with double exceptionality are those who present two out of the ordinary conditions: one associated with outstanding skill and the other associated with a disability. This study sought to determine a profile of executive functioning and subjective well-being of students with double exceptionality (DE) which presented both above-average intelligence and Autism Spectrum Disorder (ASD). The results were compared with a control group of equally numbered students. The students were paired by sex, age, and socio-economic level. Through a quantitative, descriptive, comparative and cross-cutting method, 10 males were evaluated: five DE students (M=12.65 [4.18]) and five control group Students (M=12.48 [4.10]). The results of executive functioning show that DE Students present higher performance in Fluid Reasoning (p=0.04) and, according to teachers’ perception, a better Inhibitory Control (p=0.04). Although no other significative differences were found between groups, DE students' profile did show a deficiency in executive functioning, but only in its behavioral manifestation. Results associated with subjective well-being didn’t show any significative differences between groups. DE students' profile reflects that they maintain moderate satisfaction with life and higher positive affect than negative.Los estudiantes con doble excepcionalidad son alumnos que presentan dos condiciones fuera de lo común, típicamente una condición asociada a talento y otra condición a discapacidad. Este estudio buscó determinar un perfil de funcionamiento ejecutivo (FE) y bienestar subjetivo (BS) de alumnos con doble excepcionalidad (DE) que presentan trastorno del espectro autista (TEA) e inteligencia sobre el rango promedio, para compararlo con estudiantes con desarrollo normativo e inteligencia Promedio de la comuna de Concepción. Los alumnos fueron pareados por sexo, edad y nivel socio económico. Mediante un método cuantitativo, descriptivo, comparativo y transversal, se evaluaron a 10 varones; cinco alumnos DE (M= 12,65 [4,18]) y cinco del grupo comparativo (M=12,48 [4,10]). Al comparar funcionamiento ejecutivo entre grupos, se observó que los alumnos con DE presentan mejor desempeño en Razonamiento Fluido (p=0,04) y, según la percepción de los docentes, un mejor control Inhibitorio (p=0,04). A pesar de que no se encontraron otras diferencias significativas entre grupos, el perfil de alumnos DE si mostró un déficit en funciones ejecutivas, pero únicamente en la manifestación conductual de las mismas. Los resultados asociados al bienestar subjetivo, indican que no existen diferencias significativas entre grupos. El perfil de alumnos DE refleja que mantienen “moderada” satisfacción con la vida y mayor Afecto Positivo que Negativo

Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients

Galectin-8 belongs to a family of mammalian lectins that recognize glycoconjugates present on different cell surface components and modulate a variety of cellular processes. A role of Gal-8 in the immune system has been proposed based on its effects in immune cells, including T and B lymphocytes, as well as the presence of anti-Gal-8 autoantibodies in the prototypic autoimmune disease systemic lupus erythematosus (SLE). We have previously described that Gal-8 induces apoptosis in activated T cells interacting with certain β1 integrins and this effect is counteracted by the anti-Gal-8 autoantibodies. Given that Gal-8 can potentially interact with several glycoproteins, here we analyzed the β2 integrin Lymphocyte Function-Associated Antigen-1 (LFA-1), which is involved in leukocyte cell adhesion and immunological synapses. We show by GST-pull down assays that Gal-8 interacts with LFA-1 and this interaction is inhibited by anti-Gal-8 autoantibodies isolated from SLE patients. In cell adhesion assays, Gal-8 precluded the interaction of LFA-1 with its ligand Intracellular Adhesion Molecule-1 (ICAM-1). These results suggest that Gal-8 can exert immunosuppressive action not only by inducing apoptosis in activated T cells but also by negatively modulating the crucial function of LFA-1 in the immune system, while function-blocking autoantibodies counteract these effects

Galectin-8 promotes migration and proliferation and prevents apoptosis in U87 glioblastoma cells

BACKGROUND: Glioblastoma is one of the most aggressive cancers of the brain. Malignant traits of glioblastoma cells include elevated migration, proliferation and survival capabilities. Galectins are unconventionally secreted glycan-binding proteins that modulate processes of cell adhesion, migration, proliferation and apoptosis by interacting with beta-galactosides of cell surface glycoproteins and the extracellular matrix. Galectin-8 is one of the galectins highly expressed in glioblastoma cells. It has a unique selectivity for terminally sialylated glycans recently found enhanced in these highly malignant cells. A previous study in glioblastoma cell lines reported that Gal-8 coating a plastic surface stimulates two-dimensional motility. Because in other cells Gal-8 arrests proliferation and induces apoptosis, here we extend its study by analyzing all of these processes in a U87 glioblastoma cell mode.l METHODS: We used immunoblot and RT-PCR for Gal-8 expression analysis, recombinant Gal-8 produced in a bacteria system for Gal-8 treatment of the cells, and shRNA in lentivirus transduction for Gal-8 silencing. Cell migration as assessed in transwell filters. Cell proliferation, cell cycle and apoptosis were analyzed by FACS. RESULTS: Gal-8 as a soluble stimulus triggered chemotactic migration of U87 cells across the polycarbonate filter of transwell chambers, almost as intensively as fetal bovine serum. Unexpectedly, Gal-8 also enhanced U87 cell growth. Co-incubation of Gal-8 with lactose, which blocks galectin-glycan interactions, abrogated both effects. Immunoblot showed Gal-8 in conditioned media reflecting its secretion. U87 cells transduced with silencing shRNA in a lentiviral vector expressed and secreted 30-40 % of their normal Gal-8 levels. These cells maintained their migratory capabilities, but decreased their proliferation rate and underwent higher levels of apoptosis, as revealed by flow cytometry analysis of cell cycle, CFSE and activated caspase-3 staining. Proliferation seemed to be more sensitive than migration to Gal-8 expression levels. CONCLUSIONS: Gal-8, either secreted or exogenously enriched in the media, and acting through extracellular glycan interactions, constitutes a strong stimulus of directional migration in glioblastoma U87 cells and for the first time emerges as a factor that promotes proliferation and prevents apoptosis in cancerous cells. These properties could potentially contribute to the exaggerated malignancy of glioblastoma cells

Galectin-8 as an immunosuppressor in experimental autoimmune encephalomyelitis and a target of human early prognostic antibodies in multiple sclerosis.

Galectin-8 (Gal-8) is a member of a glycan-binding protein family that regulates the immune system, among other functions, and is a target of antibodies in autoimmune disorders. However, its role in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system (CNS), remains unknown. We study the consequences of Gal-8 silencing on lymphocyte subpopulations and the development of experimental autoimmune encephalitis (EAE), to then assess the presence and clinical meaning of anti-Gal-8 antibodies in MS patients. Lgals8/Lac-Z knock-in mice lacking Gal-8 expression have higher polarization toward Th17 cells accompanied with decreased CCR6+ and higher CXCR3+ regulatory T cells (Tregs) frequency. These conditions result in exacerbated MOG35-55 peptide-induced EAE. Gal-8 eliminates activated Th17 but not Th1 cells by apoptosis and ameliorates EAE in C57BL/6 wild-type mice. β-gal histochemistry reflecting the activity of the Gal-8 promoter revealed Gal-8 expression in a wide range of CNS regions, including high expression in the choroid-plexus. Accordingly, we detected Gal-8 in human cerebrospinal fluid, suggesting a role in the CNS immune-surveillance circuit. In addition, we show that MS patients generate function-blocking anti-Gal-8 antibodies with pathogenic potential. Such antibodies block cell adhesion and Gal-8-induced Th17 apoptosis. Furthermore, circulating anti-Gal-8 antibodies associate with relapsing-remitting MS (RRMS), and not with progressive MS phenotypes, predicting clinical disability at diagnosis within the first year of follow-up. Our results reveal that Gal-8 has an immunosuppressive protective role against autoimmune CNS inflammation, modulating the balance of Th17 and Th1 polarization and their respective Tregs. Such a role can be counteracted during RRMS by anti-Gal-8 antibodies, worsening disease prognosis. Even though anti-Gal-8 antibodies are not specific for MS, our results suggest that they could be a potential early severity biomarker in RRMS

Galectin-8 Favors the Presentation of Surface-Tethered Antigens by Stabilizing the B Cell Immune Synapse

International audienceComplete activation of B cells relies on their capacity to extract tethered antigens from immune synapses by either exerting mechanical forces or promoting their proteolytic degradation through lysosome secretion. Whether antigen extraction can also be tuned by local cues originating from the lymphoid microenvironment has not been investigated. We here show that the expression of Galectin-8-a glycan-binding protein found in the extracellular milieu, which regulates interactions between cells and matrix proteins-is increased within lymph nodes under inflammatory conditions where it enhances B cell arrest phases upon antigen recognition in vivo and promotes synapse formation during BCR recognition of immobilized antigens. Galectin-8 triggers a faster recruitment and secretion of lysosomes toward the B cell-antigen contact site, resulting in efficient extraction of immobilized antigens through a proteolytic mechanism. Thus, extracellular cues can determine how B cells sense and extract tethered antigens and thereby tune B cell responses in vivo

Detection of Gal-8 autoantibodies in sera and CSF from MS patients.

<p>Immunoblot of sera and CSF from different MS patients (Pn) against Gal-8 indicating its (-) or (+) anti-Gal-8 reactivity compared with a negative control (C) from a healthy individual. In some patients (e.g. P2 and P10) anti-Gal-8 reactivity was detected in both sera and CSF, while in others (e.g. P3) was only detected in CSF. P14 is shown only in CSF but is also positive in serum (analyzed in other immunoblot), while P15 and P17 are negative both in CSF and serum (not shown). In most patients (e.g. P4-6) only sera could be analyzed. P9 was only analyzed in CSF.</p

Function-blocking activity of anti-Gal-8 autoantibodies.

<p>(A) Anti-Gal-8(+) sera block the adhesion of PBMC to Gal-8-coated coverslips. Graph shows number of adhered cells (Average ± SE of three anti-Gal-8(-) and three anti-Gal-8(+) sera tested in triplicate) (***p<0.001; Student’s <i>t</i>-test). (B) Anti-Gal-8 autoantibodies inhibit Gal-8-induced apoptosis of Th17 cells. <i>In vitro</i> differentiated Th17 cells from IL-17A-GFP reporter mice were purified based on IL-17A expression (GFP+) and incubated with Gal-8 (20 μg/ml) in the presence of lactose, sucrose or anti-Gal-8 antibodies affinity purified from pooled serum of MS patients. The extent of apoptosis was quantified as the frequency of Annexin V+ 7AAD+ cells of the sample relative to the frequency of Annexin V+ 7AAD+ cells of the untreated control. Representative contour plots are shown in upper panels. Quantification of a representative experiment is shown in the lower panel. Values represent mean + SEM of triplicates. Data from a representative from four independent experiments is shown. **, p<0.01; ***, p < .001 by one-way ANOVA followed by Tukey’s post-hoc test.</p