1. The NET effect of novel treatments in lupus nephritis
- Author
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Kraaij, T., Kooten, C. van, Rabelink, T.J., Teng, Y.K.O., Huizinga, T.W.J., Bajema, I.M., Hak, A.E., Berger, S.P., and Leiden University
- Subjects
Cell death ,Lupus nephritis ,Neutrophils ,SLE ,Rituximab ,ANCA-associated vasculitis ,Neutrophil extracellular traps ,Belimumab - Abstract
First, we described a method to quantify NETs which has the potential to monitor autoantigen load in the setting of autoimmune diseases where NETs play a role in its pathophysiology. The use of confocal microscopy with multiple z-stacks, makes it a sensitive method. We provided a context of how NETs can be quantified in SLE and AAV. We demonstrated that not all NETs are created equally and translation of NET formation to a digital quantification creates a narrow view. We showed higher ex vivo NET formation in AAV patients with active disease compared to AAV patients with an underlying infection supporting that excessive NET formation is an autoimmune phenomenon. Also, we demonstrated that the observed excessive NET formation is independent of ANCAs.In the next part of this thesis, we focused on new treatments in lupus nephritis. Most importantly, the results of the Sybiose study are shown; a phase 2 proof-of-concept study that included 15 patients with severe, refractory SLE treated with rituximab and belimumab. We showed that RTX+BLM has the ability to reduce autoantibodies, thereby indirectly reducing excessive NET formation in SLE, presumably due to the targeting of autoreactive B cells. Further, we observed a clinical response in our patients while tapering immunosuppressive medication.
- Published
- 2020