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Objective High-functioning autism ( HFA) and schizophrenia ( SZ) are two of the main neurodevelopmental disorders, sharing several clinical dimensions and risk factors. Their exact relationship is poorly understood, and few studies have directly compared both disorders. Our aim was thus to directly compare neuroanatomy of HFA and SZ using a multimodal MRI design. Methods We scanned 79 male adult subjects with 3T MRI (23 with HFA, 24 with SZ and 32 healthy controls, with similar non-verbal IQ). We compared them using both diffusion-based whole-brain tractography and T1 voxel-based morphometry. Results HFA and SZ groups exhibited similar white matter alterations in the left fronto-occipital inferior fasciculus with a decrease in generalized fractional anisotropy compared with controls. In grey matter, the HFA group demonstrated bilateral prefrontal and anterior cingulate increases in contrast with prefrontal and left temporal reductions in SZ. Conclusion HFA and SZ may share common white matter deficits in long-range connections involved in social functions, but opposite grey matter abnormalities in frontal regions that subserve complex cognitive functions. Our results are consistent with the fronto-occipital underconnectivity theory of HFA and the altered connectivity hypothesis of SZ and suggest the existence of both associated and diametrical liabilities to these two conditions. [ABSTRACT FROM AUTHOR]

Abstract not provided [ABSTRACT FROM AUTHOR]

Purpose Autoimmune uveitis is a severe disease, responsible for approximately 10% of acquired blindness. The side effects induced by systemic steroids or immunosuppressive therapies have prompted us to search for more specific treatments. Recently, tyrosine kinase inhibitors, including imatinib and sunitinib, have shown interesting properties in several autoimmune diseases. Their immunomodulating properties make them potential interest in the treatment of autoimmune uveitis and we analyzed their therapeutic effects in the mouse model of experimental autoimmune uveitis. Methods We induced uveitis to C57BL6 mice by immunization with IRBP protein, and we performed a randomized blinded controlled trial in 30 mice treated with either sunitinib (50mg/kg/day), imatinib (50mg/kg/day) or placebo. We then compared the efficiency of these treatments by measuring the frequency and the severity of the uveitis induced. Results An effect of sunitinib in the prevention of experimental autoimmune uveitis was observed, with an average uveitis clinical score of 1.1 in the control group, 0.70 in the imatinib group (p=0.28) and 0.36 in the sunitinib group (p=0.02). This effect was confirmed by retina histological examination, with a histopathological score of 0.95 in the control group versus 0.19 (p=0.003) in the sunitinib group. We furthermore demontrasted that sunitinib efficiency is most likely related to the immunomodulation of the immune response, with a reduction in the Th17 response and an inhibition of T cell proliferation. Conclusion Thus, we report for the first time that a tyrosine kinase inhibitor can prevent experimental autoimmune uveitis or decrease its intensity. In particular, sunitinib could be considered as a potential treatment for autoimmune uveitis. [ABSTRACT FROM AUTHOR]

Objective: A disease resembling the human spondylarthropathies develops in HLA-B27-transgenic rats. This disease in rats is mediated by CD4+ T cells, but antigen-presenting cells (APCs) may also play a role. Dendritic cells (DCs) have been reported to be defective in allogeneic mixed lymphocyte culture in this model. Here, we further investigated the functional defect of APCs., Methods: DCs and B cells from nontransgenic, HLA-B27 (33-3)-transgenic, and HLA-B7 (120-4)-transgenic rats were used to stimulate T cells. Surface expression of HLA-B transgene and rat molecules on APCs and the formation of conjugates between DCs and T cells were monitored by flow cytometry., Results: We observed a strikingly defective stimulation of allogeneic and syngeneic T lymphocytes by APCs from HLA-B27 but not HLA-B7 rats, even if stimulation was driven in the presence of anti-T cell receptor (TCR) antibody. We found no evidence that HLA-B27 DCs were immature, lacked production of some diffusible factor, or produced an inhibitory factor for T cells. When comparing the levels of expression of class II major histocompatibility complex, CD2, intercellular adhesion molecule 1, lymphocyte function-associated antigen 1, B7, and CD40 molecules at the surface of DCs from 33-3, 120-4, and nontransgenic rats, we found little difference. However, HLA-B27-transgenic DCs formed fewer conjugates with T cells than did nontransgenic DCs. Furthermore, the proportion of conjugates formed between DCs and T cells, as well as the difference between nontransgenic and HLA-B27-transgenic DCs, were in large part reduced by blocking CD86 on DCs., Conclusion: We confirmed defective stimulation of T cells by APCs in HLA-B27 rats, the mechanism of which appears to implicate APC/T cell contact, independent of TCR engagement. In addition, decreased use of the CD86 costimulatory molecule by B27 DCs was observed. Impaired costimulatory function could result in a loss of tolerance toward microbial flora in this model.