title: Immune complex pathophysiology.
abstract: Antigen-antibody (Ab) interactions that lead to the formation of immune complexes (ICs) are subtle biochemical processes determining health or disease according to the outcome. Good laboratory practice (GLP)-acknowledged IC detection methods reveal that plasma levels of up to 15 microg/mL heat-aggregated immunoglobulin G (IgG) equivalents are normal, indicating the physiological role of ICs. Among the major variables that influence the equilibrium association constant Ka, are specificity and epitope density of the antigen, Ig class/subclass of the Ab, IC complement (C)-activating capacity, Fc receptor (FcR) interaction, and cytokine activation pattern. The Ka of antigen-Ab binding at approximately 20 degrees C ranges from low affinity (105) to high affinity (107-1011). Beneficial ICs serve to remove and/or neutralize infectious or toxic antigens, following an infectious attack in immune and vaccinated hosts. Circulating ICs are more prone for benefit than tissue-bound ICs, which reflect in situ formation and/or undesired deposition in tissues due to overflow from insufficient reticuloendothelial system (RES) removal. The classical textbook topic on ICs still holds true but is under revision because of the improved knowledge of effector systems, such as C, cytokine, and FcR apparatus. Therapeutic options to treat IC-associated diseases include intravenous immunoglobulins (IVIG) at their onset and monoclonal antibodies (mAb) directed at C activation products and/or cytokines.
authors.affiliation: Medical Faculty, University of Berne, Switzerland. urs.nydegger@octapharma.ch
authors.forename: Urs E
authors.initials: UE
authors.lastname: Nydegger
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology*; D001183:Arthus Reaction / Q000097:blood / Q000276:immunology / Q000473:pathology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007154:Immune System Diseases / Q000276:immunology* / Q000503:physiopathology*; D015202:Protein Engineering