Professor - Group leader
Prof. Dr. Leendert Trouw
Brief summary of research:
During my career, I have continuously focused on complement and (auto)antibodies. In my PhD-studies I became fascinated by the pathological consequences of complement and autoantibodies and was the first to show the pathogenicity of anti-C1q autoantibodies (J.Clin.Invest.2004). My post-doc studies in Sweden, revealed the importance of complement-inhibitors binding to free-DNA and dead cells (J.Exp.Med.2005). Subsequently, I choose to work (supported by a Veni-grant) in the Dept. of Rheumatology, LUMC, to implement obtained knowledge on complement and autoantibodies in a clinical setting. Several autoantibodies are known in Rheumatoid Arthritis but in 2011, with my team, I discovered a new autoantibody recognizing carbamylated-proteins (Proc.Natl.Acad.Sci.2011). During the last five years, using my Vidi-grant, I have unravelled the anti-CarP antibody response in depth and observed that they are present years before disease onset and are associated with development of RA and with disease severity. The predictive, diagnostic and prognostic properties have now been replicated in several international studies and following patenting, a commercial test is now being developed. How autoantibodies contribute to arthritis is still unknown, but I have demonstrated the complement activating potential of RA-associated antibodies. With my ERC-grant, we study the role of complement in autoantibody responses develop against modified self-proteins. In addition, I planned to use my expertise in complement and autoantibodies to develop modified-autoantibodies as therapeutics. Therefore, I have moved my group from the Rheumatology to the Immuno-Haematology (LUMC), one of the top Dutch immunology departments focusing on multiple disease areas, allowing a broad implementation of our findings.
Curriculum Vitae:
I studied Biology at Leiden University, specialising in Medical Biology and graduated in 1999. I did my PhD training with Prof. Daha at the Department of Nephrology at the Leiden University Medical Center and defended my thesis entitled ‘Pathologic significance of autoantibodies against C1q in the development of nephritis’ in 2004.
Current and previous positions:
2017-present Associate Professor, Dept. of Immunology, LUMC, Leiden
2016-2017 Associate Professor, Dept. of Rheumatology, LUMC, Leiden
2012-2016 Assistant Professor, Dept. of Rheumatology, LUMC, Leiden
2007-2012 Postdoc, Dept. of Rheumatology, LUMC, Leiden
2004-2007 Postdoc, Dept. of Clinical Chemistry, Lund University, Malmö, Sweden
Publications
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Targeted complement inhibition using bispecific antibodies that bind local antigens and endogenous complement regulators.
Wang H, van de Bovenkamp FS, Dijkstra DJ, Abendstein L, Borggreven NV, Pool J, Zuijderduijn R, Gstöttner C, Gelderman KA, Damelang T, Vidarsson G, Blom AM, Domínguez-Vega E, Parren PWHI, Sharp TH, Trouw LA.
Front Immunol. 2024 May 16;15:1288597. doi: 10.3389/fimmu.2024.1288597. eCollection 2024.
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Circulating levels of endogenous complement inhibitors correlate inversely with complement consumption in systemic lupus erythematosus.
van der Meulen S, Monahan RC, Gelderman KA, van Kooten C, Teng YKO, Huizinga TWJ, Steup-Beekman GM, Trouw LA.
Eur J Immunol. 2024 Aug 20:e2450998. doi: 10.1002/eji.202450998. Online ahead of print.
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Human anti-C1q autoantibodies bind specifically to solid-phase C1q and enhance phagocytosis but not complement activation.
Dijkstra DJ, van de Bovenkamp FS, Abendstein L, Zuijderduijn R, Pool J, Kramer CSM, Slot LM, Drijfhout JW, de Vor L, Gelderman KA, Rooijakkers SHM, Zaldumbide A, Vidarsson G, Sharp TH, Parren PWHI, Trouw LA.
Proc Natl Acad Sci U S A. 2023 Dec 12;120(50):e2310666120. doi: 10.1073/pnas.2310666120. Epub 2023 Dec 4.
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Antibodies against multiple post-translationally modified proteins aid in diagnosis of autoimmune hepatitis and associate with complete biochemical response to treatment.
van den Beukel MD, Stoelinga AEC, van der Meer AJ, van der Meulen S, Zhang L, Tushuizen ME, van Hoek B, Trouw LA.
Front Med (Lausanne). 2023 Jul 25;10:1195747. doi: 10.3389/fmed.2023.1195747. eCollection 2023
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Complement is activated by elevated IgG3 hexameric platforms and deposits C4b onto distinct antibody domains.
Abendstein L, Dijkstra DJ, Tjokrodirijo RTN, van Veelen PA, Trouw LA, Hensbergen PJ, Sharp TH.
Nat Commun. 2023 Jul 7;14(1):4027. doi: 10.1038/s41467-023-39788-5. PMID: 37419978
Groups:
Tutors | Complement and antibodies
