B Diamond

..Under conditions of BBB compromise, and during fetal development, we think that these antibodies can alter brain function in otherwise healthy individuals...

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..We discuss the implications of this model for lupus and for identifying other antibodies that may contribute to brain disease...

..These observations necessitate a new look at the many interconnections of the immune system and the brain, suggesting new frontiers for research and new therapeutic strategies for neurodevelopmental diseases...

..Thus, it might be possible to treat the aspects of autoimmune disease without inducing major immunosuppression and ensuing infectious complications...

..In conclusion, the serum titer of autoantibodies against NR2A/B subunits is an indication of the potential for neuropsychiatric manifestations during the course of the disease...

..These studies suggest that an anatomic classification scheme for neuropsychiatric SLE may facilitate research on etiopathogenesis and the design of clinical trials...

..Moreover, ineffective tolerance checkpoints may exist before and after antigen activation in SLE...

..Moreover, we discuss how B cell survival and maturation are regulated centrally prior to antigen activation and in the periphery after antigen activation to form the repertoire that generates the spectrum of circulating antibodies...

..This methodology enables us to gain insight into the development and fate of DNA-reactive B cells in individual patients with SLE and paves the way ultimately to permit better and more customized therapies...

..There are significant implications for therapy...

..Thus, the IgM polyreactive repertoire in SLE includes antibodies that may acquire pathogenic function merely by undergoing class-switch recombination to become IgG antibodies...

..These data demonstrate that FcgammaRIIB preferentially limits activation of high affinity autoreactive B cells and can influence the activation of DC through an immune complex-mediated mechanism...

..Understanding the factors that regulate antigen-activated B cell differentiation and memory cell formation has implications for both antibody-mediated autoimmune disease and protective antibody responses...

..This methodology enables us to track the development of autoreactive B cells, which recognize peptide and dsDNA, in individual patients with SLE and permits the isolation of autoreactive B cells for further characterization...

..To understand the effects of long-term BLyS inhibition in human systemic lupus erythematosus (SLE)...

..This effort is based on already existing interactions among the investigators and will be substantially strengthened by the resources provided by the Program Project...

..I.: Michael Lockshin). The overall goal of this collaborative interactive program is to develop the scientific foundation for preventative therapies for cognitive decline in SLE. ..

..Finally, the Center will include an administrative core for coordination and implementation of Center activities. ..

..It cannot be emphasized too much that this study can be performed only in the cohort of patients in the SELENA trial. Another such study will not be performed. ..

..Expertise in immunology, neurology and neuroscience are all critical to this proposal. If this model can be validated, novel approaches to preventing neuropsychiatric symptoms that occur following trauma could be explored. ..

..This application represents a multidisciplinary approach to build on a novel model for neuropsychiatric manifestations of lupus and a novel paradigm for antibody-mediated changes in cognition and behavior. ..

..We will determine if an enhanced T cell response alters the repertoire of activated B cells. These studies, in composite, will help us understand how autoreactive B cells can be activated in vivo by antigen exposure. ..

..This application represents a multidisciplinary approach to build on a novel model for neuropsychiatric manifestations of lupus and a novel paradigm for antibody-mediated changes in cognition and behavior. ..

..Expertise in immunology, neurology and neuroscience are all critical to this proposal. If this model can be validated, novel approaches to preventing neuropsychiatric symptoms that occur following trauma could be explored. ..

..This application represents a multidisciplinary approach to build on a novel model for neuropsychiatric manifestations of lupus and a novel paradigm for antibody-mediated changes in cognition and behavior. ..

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..Many investigators consider it to be the premier meeting on autoimmunity. ..

..Ultimately, we hope to develop the scientific foundation for a clinical trial of NR2 receptor antagonists to protect against cognitive decline in SLE. ..

..Finally, we will investigate the differences in B cell responsiveness to estrogen in BALB/c and C57Bl/6 mice to understand what underlies an estrogen mediated breakdown in humoral self- tolerance. ..

..PUBLIC HEALTH RELEVANCE: This proposal identifies a non-immunosuppressive strategy for the treatment of systemic lupus. ..