36 research outputs found

    Mapping autism risk loci using genetic linkage and chromosomal rearrangements.

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    International audienceAutism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs

    Interleukin-17A as a Biomarker for Bovine Tuberculosis

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    T helper 17 (Th17)-associated cytokines are integral to the immune responses to tuberculosis, initiating both protective and harmful inflammatory responses. The aim of the present study was to evaluate applied aspects of interleukin-17 (IL-17) biology in the context of Mycobacterium bovis infection of cattle. Using transcriptome sequencing (RNA-Seq), numerous Th17-associated cytokine genes (including IL-17A, IL-17F, IL-22, IL-19, and IL-27) were upregulated >9-fold in response to purified protein derivative stimulation of peripheral blood mononuclear cells from experimentally M. bovis-infected cattle. Protective vaccines elicited IL-17A, IL-17F, IL-22, and IL-27 responses. Reduced IL-17A responses by vaccine recipients, compared to nonvaccinated animals, at 2.5 weeks after M. bovis challenge correlated with reduced disease burdens. Additionally, IL-17A and interferon gamma (IFN-Îł) responses were highly correlated and exhibited similar diagnostic capacities. The present findings support the use of Th17-associated cytokines as biomarkers of infection and protection in the immune responses to bovine tuberculosis

    A novel human CD32 mAb blocks experimental immune haemolytic anaemia in Fc gamma RIIA transgenic mice

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    A fully human IgG1 kappa antibody (MDE-8) was generated, which recognised Fc-gamma receptor IIa (Fc?RIIa) molecules on CD32 transfectants, peripheral blood monocytes, polymorphonuclear cells and platelets. This antibody blocked Fc?RIIa ligand-binding via its F(ab')2 fragment. Overnight incubation of monocytes with F(ab')2 fragments of MDE-8 leads to a c. 60% decrease in cell surface expression of Fc?RIIa. MDE-8 whole antibody induced a concomitant c. 30% decrease of Fc?RI on THP-1 cells and monocytes. In humans Fc?RIIa plays an important role in the clearance of antibody-coated red blood cells in vivo. As an equivalent of Fc?RIIa does not exist in mice, the in vivo effect of MDE-8 was studied in an Fc?RIIa transgenic mouse model. In these mice, antibody-induced anaemia could readily be blocked by MDE-8. These data document a new human antibody that effectively blocks Fc?RIIa, induces modulation of both Fc?RIIa and Fc?RI from phagocytic cells, and ameliorates antibody-induced anaemia in vivo

    Exacerbation of Autoantibody-Mediated Hemolytic Anemia by Viral Infection

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    Strong enhancement of the pathogenicity of an antierythrocyte monoclonal antibody was observed after infection of mice with lactate dehydrogenase-elevating virus. While injection of the antierythrocyte antibody alone induced only moderate anemia, concomitant infection with this virus, which is harmless in most normal mice, led to a dramatic drop in the hematocrit and to death of infected animals. In vitro and in vivo analyses showed a dramatic increase in the ability of macrophages from infected mice to phagocytose antibody-coated erythrocytes. These results indicate that viruses can trigger the onset of autoimmune disease by enhancing the pathogenicity of autoantibodies. They may explain how unrelated viruses could be implicated in the etiology of autoantibody-mediated autoimmune diseases
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