ComplementRarity – Complement system in rare systemic and renal diseases: A new vision of an old system

Although the Complement System (CS) is crucial in the innate immune response to host defense and homeostasis, its abnormal and/or uncontrolled activation acts as a driver of disease and tissue injury. In the last decade, new insights into the role of CS in rare diseases, both genetically determined and acquired, have been highlighted. At the same time, new drugs targeting CS and/or related pathways have changed prognosis and therapeutic strategies of rare diseases with systemic and renal involvement and have suggested a novel idea of CS as a target in the management of immune-inflammatory disorders, including transplant rejection, and age-related conditions.

This Research Topic on “ComplementRarity” aims to offer, first, an up-to-date view on evidence and perspectives on the role of the CS from a primary mechanism to a driver of progression of rare immune-mediated diseases with systemic and renal involvement. The related issue which the Research Topic would like to work on is the novel complement-targeting therapeutic strategy: that focus is closely associated with the first one and currently represents the main point of therapeutic research in this context because of its role in improving disease course and outcome as well as quality of life of patients. It follows that the Research Topic would also like to address the relevance of “complementarity” as a multi-disciplinary approach of rare diseases with systemic and renal involvement (e.g. immune-ne¬phropathies), necessary for the diagnostic suspicion, management, and therapies. In this context, disorders characterized by dysregulations of the CS, although rare (“Complement-Rarity”), represent a well-documented model and, at the same time, an intriguing focus of ongoing research.

The areas of the proposed Research Topic are Clinical Immunology and Nephrology with the focus on primary and acquired disorders of Complement System (CS) and complement-mediated mechanisms of damage in rare systemic and renal diseases. The Research Topic “ComplementRarity” would address five main issues:

1. Primary dysfunctions of CS, genetically determined diseases: update on Hereditary Angioedema, Paroxysmal Nocturnal Hemoglobinuria, Atypical Hemolytic Uremic Syndrome, and C3 Glomerulopathy would be provided.

2. Acquired dysfunctions of CS in both rare and age-related conditions: evidence on CS in organ transplant ischemia/reperfusion injury, allograft rejection, cardiovascular risk, inflammaging, and retinal changes as a model of disease would be included.

3. CS-mediated mechanisms in systemic autoimmune diseases from the point of view of organ damage: insights on lupus nephritis, antiphospholipid syndrome, Systemic Sclerosis, and obstetric-gynecological and pediatric implications would be provided.

4. CS-mediated mechanisms in rare vasculitides with prevalent renal-lung involvement: ANCA-related vasculitides and eosinophilic disorders would be included.

5. CS-targeting therapeutic strategies and their role in changing disease course, outcomes, and quality of life of patients: a novel vision foreseeing the idea of CS-targeting drugs as a “bridge” treatment strategy to disease remission.

Random clinical trials, narrative reviews, systematic reviews with and without meta-analyses, Case Reports, Case series, original research articles, and commentaries are welcome to be submitted to this Research Topic.