title: Overview of Laboratory Testing and Clinical Presentations of Complement Deficiencies and Dysregulation.
abstract: Historically, complement disorders have been attributed to immunodeficiency associated with severe or frequent infection. More recently, however, complement has been recognized for its role in inflammation, autoimmune disorders, and vision loss. This paradigm shift requires a fundamental change in how complement testing is performed and interpreted. Here, we provide an overview of the complement pathways and summarize recent literature related to hereditary and acquired angioedema, infectious diseases, autoimmunity, and age-related macular degeneration. The impact of complement dysregulation in atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria, and C3 glomerulopathies is also described. The advent of therapeutics such as eculizumab and other complement inhibitors has driven the need to more fully understand complement to facilitate diagnosis and monitoring. In this report, we review analytical methods and discuss challenges for the clinical laboratory in measuring this complex biochemical system.
authors.affiliation: National Jewish Health, Denver, CO, United States.
authors.forename: A
authors.initials: A
authors.lastname: Frazer-Abel
authors.affiliation: Mayo Clinic, Rochester, MN, United States.
authors.forename: L
authors.initials: L
authors.lastname: Sepiashvili
authors.affiliation: Mayo Clinic, Rochester, MN, United States.
authors.forename: M M
authors.initials: MM
authors.lastname: Mbughuni
authors.affiliation: Mayo Clinic, Rochester, MN, United States. Electronic address: Willrich.MariaAlice@mayo.edu.
authors.forename: M A V
authors.initials: MA
authors.lastname: Willrich
mesh_terms: D003182:Complement C5 / Q000037:antagonists & inhibitors; D003165:Complement System Proteins / Q000032:analysis* / Q000172:deficiency / Q000502:physiology; D006801:Humans
chemical_list: D003182:Complement C5; D003165:Complement System Proteins
keywords: Acquired angioedema; Age-related macular degeneration; Alternative pathway; Atypical hemolytic uremic syndrome; C3 glomerulopathies; Classical pathway; Complement deficiency; Complement dysregulation; Complement system; Complement therapeutics; Eculizumab; HCV; Hemolytic assays; Hereditary angioedema; Lectin pathway; Lupus nephritis; Paroxysmal nocturnal hemoglobinuria; Systemic lupus erythematosus; Terminal complement complex