Epilogue: The “DAMPome” as a Key Player in the Pathogenesis of Many Human Diseases

Abstract

In the Epilogue of Part VIII, the new notions about DAMP-based diagnostics, prognostics, and therapeutics in human diseases are cursorily sketched. The premise is that any infectious or sterile cell stress and/or tissue injury—even the slightest molecular perturbation of the intra- or extracellular microenvironment—can lead to a human disorder, provided the inciting insult is severe, perpetual/constant, or chronic/repetitive, and/or the induced innate/adaptive immune response turns out to be uncontrolled and dysregulated. Depending on the nature and strength of the underlying insult, the medical picture of the diseases is more or less clear to be evaluated. For example, in a polytrauma patient, the determination of DAMPs in the blood will soon give information about the magnitude of lesions caused by the previous accident and may warn the intensive care physician about the development of a life-threatening multiple organ failure, if not immediately treated. Regarding cerebro-cardiovascular accidents, for instance, myocardial infarction, the measurement of DAMPs may be helpful in assessing the additional damage of the myocardium caused by subsequent reperfusion and, thus, may call for an “anti-DAMP treatment.” Metabolic diseases reflect another scenario. For example, type 2 diabetes represents a prototypical innate immune disease where DAMP-induced, PRM-triggered sterile autoinflammatory processes in islets lead to β cell dysfunction and ultimately cell death in the form of pyroptosis. The phenomenon of stress-induced innate immune-mediated inflammation is also encountered in neurodegenerative diseases. For example, DAMPs such as amyloid β, “ASC specks,” HMGB1, and the S100 proteins represent vital components of the innate immune reaction observed in Alzheimer patients and have opened a new avenue for therapeutic intervention. These few clinical examples should just give a first vague impression on the role of DAMPs in human diseases and, in this context, may give rise to talk about the role of the “DAMPome” in human diseases. This topic will be described in Volume 2 of the book in detail by discussing the currently available international literature.