NET-ting the autoreactive B cell memory by therapeutically targeting the humoral autoimmunity in patients with SLE

Concept

Patients with SLE typically have circulating autoantibodies against nuclear autoanti- gens, such as DNA, as a result of a humoral autoimmune response. This research project intends to comprehensively study the humoral autoimmune response in SLE patients. To do so, we intend to establish an in-depth understanding of the origins of SLE-specific autoantibodies in a unique cohort of SLE patients who are treated with new biological therapies specifically targeted at the formation of autoantibodies.

Facts and figures

Project lead
Y K O Teng
UMC Leiden
y.k.o.teng@lumc.nl
FOREUM research grant: € 300.000
2016 - 2019

Meet the team

Y K O Teng
UMC Leiden
L van Dam
UMC Leiden
R Voll
Albert Ludwig University Freiburg
D Isenberg
University College London

Objectives

This consortium aims to investigate the humoral autoimmune response in three different SLE patient cohorts treated with specific B cell-targeted therapies, i.e. Rituximab, Bortezomib and their combination.

The humoral autoimmune response will be studied on different aspects in SLE patients before and after therapy, as follows: The induction of neutrophil extracellular traps to quantify the autoantigenic load of nuclear material; Degradation of neutrophil extracellular traps by SLE sera to quantify the autoantigenic load of nuclear material; Autoantibodies recognizing dsDNA, nucleosomes, histones, alphaenolase and C1q to quantify the humoral autoimmune products; Autoantigen-specific B cells recognizing dsDNA, nucleosomes, histones, alphaenolase and C1q to quantify the humoral autoimmune memory.

Patient voice

The experimental nature of our research proposal limits the potential contribution of patient research partners. It is however noteworthy that patient representatives are involved in the separate clinical trials at each collaborating centre which investigate therapeutic strategies that specifically target humoral autoimmunity.

Interim results

Patients with SLE typically have circulating autoantibodies against DNA as a result of a humoral (auto-)immune response. This research project intends to  comprehensively study the pathophysiology of the humoral autoimmune response in SLE patients to establish an in-depth understanding of how autoantibodies  develop in  a unique cohort of SLE patients who are treated with new biological therapies specifically targeted at the formation of  autoantibodies. We have identified 38 refractory SLE patients with renal involvement who were treated with experimental treamtment regimens (i.e. rituximab, bortezomib or combination rituximab + belimumab). We are well on our way to perform in-depth analyses in these patients which eventually will inform us if and how these novel treatments influence the formation of autoantibodies in SLE patients.

Publications

  • Laura S. van Dam, Eline J. Arends, Tineke Kraaij, Sylvia W.A. Kamerling, Ton J. Rabelink, Cees van Kooten, Y.K. Onno Teng. A high-throughput assay to assess and quantify neutrophil extracellular trap formation. J Vis Exp. 2019 Jan 29;(143). doi: 10.3791/59150.
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  • Van Dam L, Osmani Z, Kraaij T, et al. FRI0311 The effect of b cell targeted therapies on autoantibodies and excessive neutrophil extracellular trap formation in systemic lupus erythematosus patients. Annals of the Rheumatic Diseases 2018;77:692.
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  • Laura S. van Dam, Ton J. Rabelink, Cees van Kooten, Y.K. Onno Teng. Clinical implications of excessive neutrophil extracellular trap formation in renal autoimmune diseases. Kidney Int Rep. 2018 Nov 19;4(2):196-211. doi: 10.1016/j.ekir.2018.11.005.
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  • Dam LV, Kraaij T, Kamerling S, et al. SAT0015 Anca-associated vasculitis- and systemic lupus erythematosus-induced neutrophil extracellular traps have intrinsically different features. Annals of the Rheumatic Diseases 2017;76:774.
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  • Dam LV, Kraaij T, Kamerling S, et al. SAT0015 Anca-associated vasculitis- and systemic lupus erythematosus-induced neutrophil extracellular traps have intrinsically different features. Annals of the Rheumatic Diseases 2017;76:774.
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