Michaëla A M Huson1, Diana Wouters2, Gerard van Mierlo2, Martin P Grobusch3, Sacha S Zeerleder4, Tom van der Poll5. 1. Center of Experimental and Molecular Medicine Center of Tropical Medicine and Travel Medicine, Division of Infectious Diseases Centre des Recherches Médicales de Lambaréné, Gabon. 2. Department of Immunopathology, Sanquin Blood Supply Division of Research, Joint Academic Medical Center-Sanquin Landsteiner Laboratory, Amsterdam, The Netherlands. 3. 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. 4. 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. 5. Center of Experimental and Molecular Medicine.
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.
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-infectedpatients 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: Anna E van Beek; Richard B Pouw; Victoria J Wright; Neneh Sallah; David Inwald; Clive Hoggart; Mieke C Brouwer; Rachel Galassini; John Thomas; Leo Calvo-Bado; Colin G Fink; Ilse Jongerius; Martin Hibberd; Diana Wouters; Michael Levin; Taco W Kuijpers Journal: Front Immunol Date: 2022-05-26 Impact factor: 8.786
Authors: Michaëla A M Huson; Brendon P Scicluna; Lonneke A van Vught; Maryse A Wiewel; Arie J Hoogendijk; Olaf L Cremer; Marc J M Bonten; Marcus J Schultz; Marek Franitza; Mohammad R Toliat; Peter Nürnberg; Martin P Grobusch; Tom van der Poll Journal: PLoS One Date: 2016-02-12 Impact factor: 3.240
Authors: Thomas C Morris; Clive J Hoggart; Novel N Chegou; Martin Kidd; Tolu Oni; Rene Goliath; Katalin A Wilkinson; Hazel M Dockrell; Lifted Sichali; Louis Banda; Amelia C Crampin; Neil French; Gerhard Walzl; Michael Levin; Robert J Wilkinson; Melissa S Hamilton Journal: Front Immunol Date: 2021-02-25 Impact factor: 7.561
Authors: Michaëla A M Huson; Arie J Hoogendijk; Alex F de Vos; Martin P Grobusch; Tom van der Poll Journal: J Int AIDS Soc Date: 2016-05-16 Impact factor: 5.396
Authors: Mehran Alizadeh Aghdam; Mignon van den Elzen; Harmieke van Os-Medendorp; Marijke R van Dijk; Edward F Knol; André C Knulst; Heike Röckmann; Henny G Otten Journal: Clin Transl Allergy Date: 2021-07-03 Impact factor: 5.871