Editorial: Immune Complexes in Disease Pathology

Specialty section: This article was submitted to Alloimmunity and Transplantation, a section of the journal Frontiers in Immunology Foreign and modified self-antigens bind to natural IgM to form immune complexes (ICs). This facilitates the instructive phase of immunity, which programs immune response to generate class-switched high affinity antibodies required for IC formation, resulting in pathogen clearance. ICs are the first responders of immune challenge. However, accumulation of abnormal IC levels triggers disease pathologies such as nephropathies, autoimmunity, cancers, infections, and lung injury. ICs are dynamic in their size and composition, present either in systemic circulation or formed locally in tissue. In seven reviews in the topic " Molecular Mechanisms of Immune Complex Physiology, " the authors describe various pathological and physiological aspects of IC-driven pathologies. Krishna and Nadler summarize the consequence of ICs formed by biologics and their role in antigenicity to biotherapeutics. Knoppova et al. summarize how galactose-deficient IgA1 bound to IgG or IgA, upon forming ICs deposits in glomeruli activate mesangial cells, induce renal injury, and trigger cellular proliferation. In membranous nephropathy, autoantibodies to phospholipase A2 receptor expressed by podocytes form ICs in situ. Borza discusses how renal injury results from dysregulation of the alternate pathway of complement due to loss of heparin sulfate chains. Classical complement pathway activation by ICs results in the production of C5a, a potent anaphylatoxin, and membrane attack complex (MAC or C5b-9). Sublytic C5b-9 triggers signaling and induces growth factors and cytokine secretion in various cell types. C5b-9 in CD4 + T-cells triggers membrane rafts (MRs) clustering , a function attributed to CD28 cosignaling. MRs are membrane organelles rich in signaling proteins that play a crucial role in lymphocyte activation. Ward et al. describe in their mini-review how ICs participate in the development of acute respiratory distress syndrome and acute lung injury. These authors further describe how generation of C5a by ICs upon binding to C5aR1/C5aR2 promotes the appearance of extracellular histones, which are a major component of neutrophil extracel-lular traps (NETs). In autoimmunity, ribonucleoprotein-containing ICs induce NETosis. It is now proposed that the histone citrullination and reactive oxygen species are important for NETosis (1). Juvenile idiopathic arthritis (JIA) is characterized by the presence of elevated ICs, and IC deposits are observed in patient joints. Moore reviews the presence of ICs in JIA and discusses the role of citrullinated peptide antigens such as type II collagen and fibrinogen, which form ICs that contribute …