ComplementRarity – Complement system in rare systemic and renal diseases: evolution in therapy

The Complement System (CS), traditionally viewed as a central effector of innate immunity, is well recognized as a dynamic regulator of immune balance whose dysregulation can cause and drive tissue injury and disease progression in rare systemic and renal disorders. Over the past decade, advances in molecular understanding have changed the vision of rare and complexes CS-mediated diseases, from mechanistic curiosities into paradigmatic models of potential targeted immunotherapy.Following the first edition of “ComplementRarity,” which redefined the CS as a key driver of rare immune-mediated diseases, the present Edition of the Research Topic focuses on the evolution in therapy of such rare disorders. The rapid increase of CS-targeting drugs, pathway-selective inhibitors, and biomarker-guided strategies has dramatically changed prognosis, treatment algorithms, and quality of life for patients affected by rare CS-mediated conditions. Furthermore, evidence strongly supports the role of the CS activation as a mediator of tissue remodeling in both the acute damage and the fibrosis: in this view, CS acts as a link between inflammatory injury and early fibrotic pathways in renal, vascular, and systemic diseases. Understanding this interplay between CS activation, immune-mediated damage, and fibrogenesis opens novel therapeutic perspectives aimed at preventing end-stage organ damage.This Research Topic aims to explore:1. Therapeutic evolution in primary CS disorders, including C1-inhibitor deficiency Hereditary Angioedema, Paroxysmal Nocturnal Hemoglobinuria, Atypical Hemolytic Uremic Syndrome, and C3 Glomerulopathy, with emphasis on long-term outcomes, treatment strategies, and quality-of-life in real life evidence from these genetically determined conditions.2. Potential CS-modulation in acquired and age-related conditions, including transplant ischemia/reperfusion injury, antibody-mediated rejection, cardiovascular risk, inflammaging, and retinal microvascular disease.3. Emerging evidence on CS-mediated mechanisms in systemic autoimmune diseases, IgG4 related Diseases, and vasculitides, with a main focus on renal involvement and organ damage progression.4. The interplay between CS, inflammation, and acute fibrosis, focusing on the transition from immune activation to fibrotic remodeling and the potential role of CS-targeted strategies in this context.5. Precision medicine and future directions, including potential biomarkers of CS activation, pharmacodynamic monitoring, adaptive treatment strategies, and the role of CS-inhibitors as disease-modifying therapies.By highliting the therapeutic evolution, this Research Topic support the idea of rare CS-mediated diseases as a model of translation immunology, where mechanistic insights directly provide innovative and personalized treatment strategies.Original research articles, randomized and real-world studies, systematic and narrative reviews, case series and reports, and translational investigations bridging bench and bedside are welcome.This Research Topic is the second volume in the successful collection on "ComplementRarity – Complement system in rare systemic and renal diseases: A new vision of an old system". Please find the first volume of this Research Topic here. Topic editors: Marzena Olesinska, Paola Triggianese, Anna Paola Mitterhofer Source: https://www.frontiersin.org/research-topics/77431/complementrarity---complement-system-in-rare-systemic-and-renal-diseases-evolution-in-therapy