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.
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
Carbamylation reduces the capacity of IgG for hexamerization and complement activation.
Verheul MK, Janssen GMC, de Ru A, Stoeken-Rijsbergen G, Levarht EWN, Kwekkeboom JC, Bomer N, Ioan-Facsinay A, Meulenbelt I, Cordfunke RA, Drijfhout JW, Toes REM, van Veelen PA, Trouw LA
Clin Exp Immunol. 2020 Apr;200(1):1-11.
Expression and production of the SERPING1-encoded endogenous complement regulator C1-inhibitor in multiple cohorts of tuberculosis patients.
Lubbers R, Sutherland JS, Goletti D, de Paus RA, Dijkstra DJ, van Moorsel CHM, Veltkamp M, Vestjens SMT, Bos WJW, Petrone L, Malherbe ST, Walzl G, Gelderman KA, Groeneveld GH, Geluk A, Ottenhoff THM, Joosten SA, Trouw LA.
Mol Immunol. 2020 Apr;120:187-195.
Secretory form of rheumatoid arthritis-associated autoantibodies in serum are mainly of the IgM isotype, suggesting a continuous reactivation of autoantibody responses at mucosal surfaces.
van Delft MAM, van der Woude D, Toes REM, Trouw LA.
Ann Rheum Dis. 2019 Jan;78(1):146-148.