title: HIV Coinfection Enhances Complement Activation During Sepsis.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV)-induced complement activation may play a role in chronic immune activation in patients with HIV infection and influence the complement system during acute illness. We determined the impact of HIV infection on the complement system in patients with asymptomatic HIV infection and HIV-infected patients with sepsis or malaria.
  
  
  METHODS
  We performed a prospective observational study of 268 subjects with or without HIV infection who were asymptomatic, were septic, or had malaria. We measured complement activation products (C3bc and C4bc) and native complement proteins (C3 and C4). levels of mannose-binding lectin and C1q-C4 were measured to examine activation of the lectin and classical pathways, respectively.
  
  
  RESULTS
  Asymptomatic HIV infection was associated with increased C4 activation, especially in patients with high HIV loads, and was accompanied by elevated C1q-C4 levels. Similarly, sepsis and malaria resulted in increased C4 activation and elevated C1q-C4 concentrations. HIV coinfection enhanced C4 activation and consumption in patients with sepsis; this effect was not detected in patients with malaria. Mannose-binding lectin deficiency (defined as a mannose-binding lectin level of <500 ng/mL) did not influence complement activation in any group.
  
  
  CONCLUSIONS
  HIV activates the complement system, predominantly via the classical pathway, and causes increased C4 activation and consumption during sepsis. HIV-induced complement activation may contribute to tissue injury during chronic infection and acute intercurrent bacterial infections.
authors: Center of Experimental and Molecular Medicine Center of Tropical Medicine and Travel Medicine, Division of Infectious Diseases Centre des Recherches Médicales de Lambaréné, Gabon.
authors: Michaëla A M
authors: MA
authors: Huson
authors: Department of Immunopathology, Sanquin Blood Supply Division of Research, Joint Academic Medical Center-Sanquin Landsteiner Laboratory, Amsterdam, The Netherlands.
authors: Diana
authors: D
authors: Wouters
authors: Department of Immunopathology, Sanquin Blood Supply Division of Research, Joint Academic Medical Center-Sanquin Landsteiner Laboratory, Amsterdam, The Netherlands.
authors: Gerard
authors: G
authors: van Mierlo
authors: Center of Tropical Medicine and Travel Medicine, Division of Infectious Diseases Centre des Recherches Médicales de Lambaréné, Gabon Institute of Tropical Medicine, University of Tübingen, Germany.
authors: Martin P
authors: MP
authors: Grobusch
authors: Department of Hematology, Academic Medical Center, University of Amsterdam Department of Immunopathology, Sanquin Blood Supply Division of Research, Joint Academic Medical Center-Sanquin Landsteiner Laboratory, Amsterdam, The Netherlands.
authors: Sacha S
authors: SS
authors: Zeerleder
authors: Center of Experimental and Molecular Medicine.
authors: Tom
authors: T
authors: van der Poll
mesh_terms: D000328:Adult; D060085:Coinfection / Q000276:immunology* / Q000382:microbiology* / Q000503:physiopathology / Q000821:virology; D003167:Complement Activation; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000382:microbiology* / Q000503:physiopathology / Q000821:virology; D006801:Humans; D008288:Malaria / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology / Q000821:virology; D055815:Young Adult
keywords: HIV; complement system proteins; malaria; mannose-binding lectin; sepsis