Complement & pentraxin immunity: mechanisms, disease pathogenesis, and therapeutic opportunities

The complement system is a cornerstone of innate immunity - an evolutionarily ancient yet remarkably versatile effector network that eliminates pathogens, clears apoptotic debris, and orchestrates the transition between innate and adaptive immune responses. Its influence extends into tissue homeostasis, synaptic pruning, and the regulation of inflammatory resolution. Pentraxins - a superfamily of soluble pattern recognition molecules encompassing the short pentraxins CRP and SAP, and the long pentraxins PTX3, PTX4, and the neuronal pentraxins - are functionally coupled to complement at multiple regulatory checkpoints. By engaging complement initiating molecules and regulatory proteins alike, pentraxins act as context-dependent rheostats that amplify or restrain complement activity, thereby shaping inflammatory outcomes across a wide range of physiological and pathological settings.Dysregulation of complement and pentraxin pathways underlies a striking breadth of human disease - from sepsis and autoimmune disorders to neurodegeneration, atherosclerosis, and cancer. Yet despite mounting recognition of complement-pentraxin crosstalk as a functionally coherent axis, its mechanistic architecture, context-specific behavior, and therapeutic tractability remain incompletely defined. The field is now at an inflection point. Structural and cryo-EM studies are resolving complement-pentraxin interaction interfaces at atomic resolution. Multi-omics strategies are mapping pathway activity across disease states with new granularity. Clinical trials of complement-targeted biologics - including inhibitors of C3, C5, factor B, and factor D - are generating translational insights that demand mechanistic interpretation. Simultaneously, CRP and PTX3 are gaining traction as dynamic biomarkers in neuroinflammation, cardiovascular risk, and infectious disease. This Research Topic brings together cutting-edge mechanistic studies, translational findings, and emerging therapeutic concepts to build a comprehensive picture of how complement and pentraxin networks intersect in health and disease — and how that intersection can be exploited for patient benefit.We welcome contributions from immunologists, structural biologists, clinicians, and translational researchers working at the forefront of complement and pentraxin biology. This Research Topic invites Original Research, Reviews, Mini-Reviews, Perspectives, Commentaries, and Opinion articles addressing, but not limited to, the following themes:• Structural and mechanistic basis of pentraxin-complement interactions, including pathway activation, regulation, and immune evasion• Complement-pentraxin crosstalk in host defense against bacterial, viral, and fungal pathogens• Contributions of the complement-pentraxin axis to autoimmune and systemic inflammatory diseases, including lupus, rheumatoid arthritis, and vasculitis• Roles of complement and pentraxins in neurodegeneration and neuroinflammation, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis• Complement and pentraxin biology in cardiovascular pathology, ischemia-reperfusion injury, and metabolic disease• Pentraxins as biomarkers and modulators of complement-mediated pathology in infection and cancer• Complement-targeted therapeutics: mechanisms, resistance, and opportunities for combination strategies involving pentraxin biology Topic editors: Ying Jie Ma, Marina Noris Source: https://www.frontiersin.org/research-topics/85665/complement-pentraxin-immunity-mechanisms-disease-pathogenesis-and-therapeutic-opportunities