Virginia Pascual

..In this issue of Immunity, Gall et al. (2012) characterize, in a murine model of autoimmunity, the origin and progression of the type I interferon response leading to disease...

..This novel information is leading to the development of IFN antagonists as a potential therapeutic intervention in SLE, thus bringing hope to SLE patients...

..We expect this to crystallize within the coming decade, as these methods become part of the personalized medicine armamentarium...

..This review summarizes the recently uncovered role of dendritic cell subsets and one of their products, interferon-alpha, in the pathophysiology of systemic lupus erythematosus...

..We conclude that IL-1 is a major mediator of the inflammatory cascade that underlies SoJIA and that this cytokine represents a target for therapy in this disease...

..Finally, our pilot clinical trials using IL-1 blockers have shown remarkable clinical benefits in SoJIA patients refractory to other medications...

..Availability of early diagnostic markers may allow prompt initiation of therapy and prevention of disabilities...

..It may also provide an explanation for spreading of the autoimmune repertoire as autoimmunity develops...

..Indeed, what we learn from studying autoimmunity will help us induce strong vaccine specific immunity, either protective, as in the case of microbes, or therapeutic, as in the case of tumors...

..Collectively, our study suggests that a direct myeloid DC-B cell interplay might contribute to the pathogenesis of SLE...

..Blood gene expression profiling can be used to identify such biomarkers. This review will summarize recent studies in the field and will discuss some of the challenges raised by the use of this technology in biomarker discovery...

..In this article, we summarize our recent studies aimed at a better understanding of the DC system to unravel the pathophysiology of human diseases and design novel human vaccines...

..Thus, our results reveal a novel dialog between Ms and B cells, in which IP-10 acts as a PC differentiation factor...

..These findings bring new perspectives for the application of blood leukocyte expression signatures for diagnosis and early disease detection...

..These plasma cells display the high levels of CD38 found on tissue plasma cells. Thus, pDCs are critical for the generation of plasma cells and antibody responses...

..Our results reveal an unsuspected role for neutrophils in SLE pathogenesis and identify a novel link between nucleic acid-recognizing antibodies and type I IFN production in this disease...

..These results, therefore, might provide a mechanistic explanation for the development of anti-dsDNA antibodies and lupus-like syndrome in patients undergoing anti-TNF therapy...

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..Therefore, while the IFN signature confirms the central role of this cytokine in SLE, microarray analysis of blood cells reveals that immature granulocytes may be involved in SLE pathogenesis...

..Thus, this work describes the implementation and application of a methodology designed to support systems-scale analysis of the human immune system in translational research settings...

..Recent technological and methodological advances that will carry the blood transcriptome research field forward are also discussed...

..50% of SLE patients have high serum levels of IFNalpha, which could explain T/B lymphopenia. Yet, plasmacytoid DCs, a major IFNalpha source, are 80% decreased. pDCs and IFNalpha may play a role in SLE pathogenesis and therapy...

..This model complements the Type 1/Type 2 paradigm. Therefore, immunity can be viewed as a dynamic system driven by two sets of opposite vectors: IFN-alpha/beta/TNF and IFN-gamma/IL-4...

..Another pathway includes plasmacytoid DCs, which promptly secrete large amounts of IFN-alpha/beta viral encounter. Thus, insights into in vivo DC functions are important to understand the launching and modulation of immunity...

..Alterations of the DC system result in diseases such as autoimmunity, allergy, and cancer. Conversely, DCs can be exploited for vaccination, and novel vaccines that directly target DCs in vivo are being designed...

..Thus, our work provides new insights into effectiveness and limitations of the current SLE therapies...

..Clinical trials to test several of these novel therapies are currently underway...

..Importantly, the skewing of subsets correlated with disease activity and frequency of blood plasmablasts. Collectively, our study suggests that an altered balance of Tfh cell subsets contributes to human autoimmunity...

..Although IFN-alpha remains at the center of immunologic aberrations in SLE, it remains to be determined whether increased shedding of soluble TNF receptors could also be ascribed to IFN-alpha...

..We also emphasize how information accumulated through in vitro as well as in vivo studies of genetically engineered mice can help in the understanding and treatment of human diseases...

..Genetic alterations in lineages other than B cells might explain other autoimmune syndromes where type I IFNs appear to be involved...

..Understanding its unique pathogenesis will hopefully lead to the development of better, more targeted and less toxic therapies...

..Understanding the mechanisms that underlie neutrophil activation, migration, survival and their various forms of death in health and disease might provide us with new approaches to treat chronic inflammatory conditions...

..A dramatic improvement in his pyoderma gangrenosum was observed after one infusion of infliximab, and a second infusion led to its resolution. Our observation extends the therapeutic use of infliximab to this component of PAPA syndrome...

..Study of the antigens reacting with monoclonal IgMs may provide further insight into the pathogenesis of WM...

..Taken together, our results show that human GC B cells differ from naive and memory B cells by their aggregated MIIC that lack HLA-DO...

..This component will also maintain a website with video files from the Symposia and Workshops. A five person external Advisory Committee is in place to serve the program. ..

..Our ultimate goal is to design novel therapies to antagonize the causative agent and/or the genetic pathways responsible for the establishment of this intriguing disease. ..

..3. To identify the + _ nature and function of the SLE-restricted CD19- CD20- cell populations that co-purify with B cells. 4. To determine the clinical relevance of the + _ accumulation f IgD+ CD38+ B cells and/or CD19- CD20- cells. ..

..humanimmunologybiodefense.com?) will be created. Three components will be proposed on the Website: Standard Operating Procedures, Human Immunology and Infectious Diseases Reviews, and Symposium recording. ..

..These studies may help reaching a better understanding of the connections between the processes of normal B cell differentiation and the development of germinal center malignancies. ..

..Understanding the basis of IL-1 dysregulation might shed light on very basic aspects of cytokine biology and help finding novel therapeutic targets for this disease. ..