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This record contains raw data related to article “Pressure Overload induces a self-antigen-driven, autoimmune-like mechanism, permitting preventive Heart Failure vaccine therapy in mice"

Abstract: Background Heart Failure (HF) is strongly associated with inflammation. In pressure overload (PO)-induced HF, cardiac stress triggers adaptive immunity, ablation or inhibition of which blocks disease progression. We hypothesized that PO HF might fulfill the formal criteria of autoimmunity: if so, the associated adaptive immune response would be not only necessary but also sufficient to induce HF; it should also be possible to identify self-antigens driving the autoimmune response. Finally, we hypothesized that such an antigen-specific response can be manipulated to preventively reduce severity of PO-HF, in a tolerizing vaccine. Methods  We used transfer of lymphocytes or serum from PO-HF mice into healthy recipients, to assess whether the adaptive response is sufficient to induce disease. We devised a novel pipeline to identify self-antigens driving the response. We immunized healthy mice with the novel antigens to assess whether they induce disease. To determine whether these antigens could be present in human patients, we sought to detect existing responses against these antigens in HF patients. Finally, we used the antigens in an oral tolerance protocol to preventively protect mice from subsequently-induced PO HF, analyzing the results with next generation sequencing. Results We found that PO-HF fulfills criteria of an autoimmune disease, albeit partially, and identified novel cardiac self-antigens, capable of inducing cardiac dysfunction. The novel antigens in a tolerizing vaccine formulation pre-emptively reduced the severity of disease triggered by subsequent application of PO, via induction of effector regulatory T cells, enabling a potent reduction of PO-driven loss of systolic function, cardiac inflammation and pro-inflammatory CD4+ T cell expansion. Conclusions We demonstrate that PO HF is triggered by hemodynamic stress and then sets off an autoimmune-like response against cardiac self-antigens. The antigens can be used to reduce severity of future-onset disease, via oral tolerization, effectively acting as a protective vaccine.