I. Jongerius PhD publications

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Publications PhD I. Jongerius

Positions
Associate Professor, Research Associate
Main activities
Education, Research
Specialisation
Complement Research, Immunology
Focus of research

Research lines

Characterization of alternative complement pathway regulator Factor H and Factor H related proteins

Factor H (FH) is an abundant plasma glycoprotein, and is the main regulator of the alternative complement pathway. FH serves as a cofactor for Factor I (FI) in the inactivation of C3b to iC3b and has decay-accelerating activity towards C3 convertases. FH binds to host cell surfaces, by binding to host specific glycosaminoglycans (GAGs) on the cell surface following initial complement activation and targets C3b to inhibit further complement activation. Dysfunctional FH may lead to severe inflammatory disease due to uncontrolled complement activation on the endothelial cells of the vasculature. As the major inhibitor of the alternative pathway of complement, FH may potentially be used as therapeutic agent for several complement mediated human diseases.

We have developed a purification strategy to isolate functional FH from human plasma. In addition, in close collaboration with Prof. T.W. Kuijpers (AMC-UMC) and Dr. T. Rispens (Sansquin) we have developed several antibodies against FH and Factor H Related proteins (FHRs). We investigate FH and FHRs levels and function in health and disease. In addition, we have developed a novel specific monoclonal antibody that potentiates the function of FH on human cell surfaces.

Complement activation and regulation on red blood cells

All healthy human cells are equipped with several surface complement regulators to prevent damage through unwanted complement activation. Endothelial cells and blood cells are particularly well protected, as these are constantly exposed to the complement system in plasma. Red blood cells (RBCs) bear all membrane complement regulators, except CD46, which is only expressed on nucleated cells

Various diseases are associated with complement mediated RBC destruction, which may be antibody mediated (autoimmune hemolytic anemia (AIHA), allo-immunization) or the result of defective complement regulation (atypical hemolytic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH)). Disease severity and response to existing complement inhibiting therapeutics is variable in these patients. This illustrates the urgent need to better understand both the triggering mechanisms of complement activation in these diseases and how the balance of complement activation and regulation on different cell surfaces is maintained.

We are investigating how RBCs are protected from unwanted complement activation, both in normal and pathological conditions, e.g. in AIHA and PNH. To answer our research questions we make use of a human cell line (HAP1) that is genetically engineered by CRISPR/Cas9 technology to lose one or several complement regulators (collaboration with Dr. R. Spaapen, Sanquin). Furthermore, we use isolated RBCs from healthy donors and PNH patients and plasma samples of AIHA patients.

Amsterdam UMC Research Institutes
AMC departments
All publications

2021

  • Zeerleder Sacha, Engel Ruchira, Zhang Tao, Roem Dorina, van Mierlo Gerard, Wagenaar‐bos Ineke, van Ham Sija Marieke, Wuhrer Manfred, Wouters Diana, Jongerius Ilse Sugar matters: Improving in vivo clearance rate of highly glycosylated recombinant plasma proteins for therapeutic use Pharmaceuticals 2021;14 (1):1-13 [PubMed]

2020

  • Baas Inge, Delvasto-Nuñez Laura, Ligthart Peter, Brouwer Conny, Folman Claudia, Reis Edimara S., Ricklin Daniel, Lambris John D., Wouters Diana, de Haas Masja, Jongerius Ilse, Zeerleder Sacha S. Complement C3 inhibition by compstatin Cp40 prevents intra- and extravascular hemolysis of red blood cells Haematologica 2020;105 (2):e57-e60 [PubMed]
  • Urban Aleksandra, Volokhina Elena, Felberg Anna, Stasiłojć Grzegorz, Blom Anna M., Jongerius Ilse, van den Heuvel Lambertus, Thiel Marcel, Ołdziej Stanisław, Arjona Emilia, de Córdoba Santiago Rodriguez, Okrój Marcin Gain-of-function mutation in complement C2 protein identified in a patient with aHUS Journal of allergy and clinical immunology 2020;146 (4):916-919.e11 [PubMed]
  • Tromp Angelino T., Zhao Yuxi, Jongerius Ilse, Heezius Erik C. J. M., Abrial Pauline, Ruyken Maartje, van Strijp Jos A. G., de Haas Carla J. C., Spaan András N., van Kessel Kok P. M., Henry Thomas, Haas Pieter-Jan A. Pre-existing antibody-mediated adverse effects prevent the clinical development of a bacterial anti-inflammatory protein Disease models & mechanisms 2020;13 (9) [PubMed]
  • de Boer Esther C. W., van Mourik Anouk G., Jongerius Ilse Therapeutic Lessons to be Learned From the Role of Complement Regulators as Double-Edged Sword in Health and Disease Frontiers in immunology 2020;11 [PubMed]
  • Dekkers Gillian, Brouwer Mieke C., Jeremiasse Jorn, Kamp Angela, Biggs Robyn M., van Mierlo Gerard, Lauder Scott, Katti Suresh, Kuijpers Taco W., Rispens Theo, Jongerius Ilse Unraveling the Effect of a Potentiating Anti-Factor H Antibody on Atypical Hemolytic Uremic Syndrome-Associated Factor H Variants Journal of immunology (Baltimore, Md. 2020;205 (7):1778-1786 [PubMed]

2019

  • Rijkers Maaike, Schmidt David, Lu Nina, Kramer Cynthia S M, Heidt Sebastiaan, Mulder Arend, Porcelijn Leendert, Claas Frans H J, Leebeek Frank W G, Jansen A J Gerard, Jongerius Ilse, Zeerleder Sacha S, Vidarsson Gestur, Voorberg Jan, de Haas Masja Anti-HLA antibodies with complementary and synergistic interaction geometries promote classical complement activation on platelets Haematologica 2019;104 (2):403-416 [PubMed]
  • Jongerius Ilse, Porcelijn Leendert, van Beek Anna E., Semple John W., van der Schoot C. Ellen, Vlaar Alexander P. J., Kapur Rick The Role of Complement in Transfusion-Related Acute Lung Injury Transfusion medicine reviews 2019;33 (4):236-242 [PubMed]

2018

  • Hovingh Elise Sofie, Mariman Rob, Solans Luis, Hijdra Daniëlle, Hamstra Hendrik-Jan, Jongerius Ilse, van Gent Marjolein, Mooi Frits, Locht Camille, Pinelli Elena Bordetella pertussis pertactin knock-out strains reveal immunomodulatory properties of this virulence factor Emerging microbes and infections 2018;7 (1):39 [PubMed]
  • Hovingh Elise S., Kuipers Betsy, Bonačić Marinović Axel A., Jan Hamstra Hendrik, Hijdra Danielle, Mughini Gras Lapo, van Twillert Inonge, Jongerius Ilse, van Els Cecile A. C. M., Pinelli Elena Detection of opsonizing antibodies directed against a recently circulating Bordetella pertussis strain in paired plasma samples from symptomatic and recovered pertussis patients Scientific reports 2018;8 (1) [PubMed]
  • van Beek Anna E., Kamp Angela, Kruithof Simone, Nieuwenhuys Ed J., Wouters Diana, Jongerius Ilse, Rispens Theo, Kuijpers Taco W., Gelderman Kyra A. Reference intervals of factor H and factor H-related proteins in healthy children Frontiers in immunology 2018;9 (AUG) [PubMed]
  • Hollingshead S, Jongerius I, Exley R M, Johnson S, Lea S M, Tang C M Structure-based design of chimeric antigens for multivalent protein vaccines Nature communications 2018;9 (1):1051 [PubMed]
  • Hovingh Elise S. Unraveling the interactions between Borderella pertussis and the innate immune system 2018. 246p. ISBN 9789402809343. [UvA Dissertations Online] Utrecht University. (Supervisor: van Strijp J. A. G.; Co-supervisors: Pinelli E., Jongerius Ilse)
  • Hovingh Elise S., de Maat Steven, Cloherty Alexandra P. M., Johnson Steven, Pinelli Elena, Maas Coen, Jongerius Ilse Virulence associated gene 8 of Bordetella pertussis enhances contact system activity by inhibiting the regulatory function of complement regulator C1 inhibitor Frontiers in immunology 2018;9 (JUN) [PubMed]

2017

  • Hovingh Elise S., van den Broek Bryan, Kuipers Betsy, Pinelli Elena, Rooijakkers Suzan H. M., Jongerius Ilse Acquisition of C1 inhibitor by Bordetella pertussis virulence associated gene 8 results in C2 and C4 consumption away from the bacterial surface PLoS pathogens 2017;13 (7) [PubMed]

2016

  • Hovingh Elise S, van den Broek Bryan, Jongerius Ilse Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion Frontiers in microbiology 2016;7:2004 [PubMed]

2015

  • Jongerius Ilse, Schuijt Tim J, Mooi Frits R, Pinelli Elena Complement evasion by Bordetella pertussis: implications for improving current vaccines Journal of molecular medicine (Berlin, Germany) 2015;93 (4):395-402 [PubMed]

2014

  • van der Veen Stijn, Johnson Steven, Jongerius Ilse, Malik Talat, Genovese Alessia, Santini Laura, Staunton David, Ufret-Vincenty Rafael L, Pickering Matthew C, Lea Susan M, Tang Christoph M Nonfunctional variant 3 factor H binding proteins as meningococcal vaccine candidates Infection and immunity 2014;82 (3):1157-63 [PubMed]

2013

  • Jongerius Ilse, Lavender Hayley, Tan Lionel, Ruivo Nicola, Exley Rachel M, Caesar Joseph J E, Lea Susan M, Johnson Steven, Tang Christoph M Distinct binding and immunogenic properties of the gonococcal homologue of meningococcal factor h binding protein PLoS pathogens 2013;9 (8):e1003528 [PubMed]
  • Ko Ya-Ping, Kuipers Annemarie, Freitag Claudia M, Jongerius Ilse, Medina Eva, van Rooijen Willemien J, Spaan András N, van Kessel Kok P M, Höök Magnus, Rooijakkers Suzan H M Phagocytosis escape by a Staphylococcus aureus protein that connects complement and coagulation proteins at the bacterial surface PLoS pathogens 2013;9 (12):e1003816 [PubMed]
  • Amdahl Hanne, Jongerius Ilse, Meri Taru, Pasanen Tanja, Hyvärinen Satu, Haapasalo Karita, van Strijp Jos A, Rooijakkers Suzan H, Jokiranta T Sakari Staphylococcal Ecb protein and host complement regulator factor H enhance functions of each other in bacterial immune evasion Journal of immunology (Baltimore, Md. 2013;191 (4):1775-84 [PubMed]

2012

  • Jongerius Ilse, von Köckritz-Blickwede Maren, Horsburgh Malcolm J, Ruyken Maartje, Nizet Victor, Rooijakkers Suzan H M Staphylococcus aureus virulence is enhanced by secreted factors that block innate immune defenses Journal of innate immunity 2012;4 (3):301-11 [PubMed]

2010

  • Stork Michiel, Bos Martine P, Jongerius Ilse, de Kok Natasja, Schilders Ingrid, Weynants Vincent E, Poolman Jan T, Tommassen Jan An outer membrane receptor of Neisseria meningitidis involved in zinc acquisition with vaccine potential PLoS pathogens 2010;6:e1000969 [PubMed]
  • Jongerius Ilse, Garcia Brandon L, Geisbrecht Brian V, van Strijp Jos A G, Rooijakkers Suzan H M Convertase inhibitory properties of Staphylococcal extracellular complement-binding protein Journal of biological chemistry 2010;285 (20):14973-9 [PubMed]
  • Roussel-Jazédé Virginie, Jongerius Ilse, Bos Martine P, Tommassen Jan, van Ulsen Peter NalP-mediated proteolytic release of lactoferrin-binding protein B from the meningococcal cell surface Infection and immunity 2010;78 (7):3083-9 [PubMed]
  • ten Broeke-Smits Nicole J P, Pronk Tessa E, Jongerius Ilse, Bruning Oskar, Wittink Floyd R, Breit Timo M, van Strijp Jos A G, Fluit Ad C, Boel C H Edwin Operon structure of Staphylococcus aureus Nucleic acids research 2010;38 (10):3263-74 [PubMed]
  • Jongerius Ilse, Puister Manon, Wu Jin, Ruyken Maartje, van Strijp Jos A G, Rooijakkers Suzan H M Staphylococcal complement inhibitor modulates phagocyte responses by dimerization of convertases Journal of immunology (Baltimore, Md. 2010;184 (1):420-5 [PubMed]

2009

  • Jongerius Ilse, Ram Sanjay, Rooijakkers Suzan Bacterial complement escape Advances in experimental medicine and biology 2009;666:32-48 [PubMed]

2007

  • Jongerius Ilse, Köhl Jörg, Pandey Manoj K, Ruyken Maartje, van Kessel Kok P M, van Strijp Jos A G, Rooijakkers Suzan H M Staphylococcal complement evasion by various convertase-blocking molecules Journal of experimental medicine 2007;204 (10):2461-71 [PubMed]
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