Refractory lupus nephritis: a tissue-based pathophysiological approach performed within the frame of a clinical trial designed to test the efficacy of rituximab

Objectives of the Project

Lupus nephritis (LN) remains a severe complication of SLE. Several studies have demonstrated that an absence of early response to therapy is a poor long-term renal prognostic factor and special care should be given to these patients.

In order to test the efficacy of rituximab (RTX) in this niche indication, an investigator-initiated trial, entitled RING, was designed. REFRACT is a RING sub-study in which baseline and 6-month repeat renal biopsy will be performed. Cells infiltrating the kidneys, especially B-cells responsible for autoantibody production, will be scrutinized (flow cytometry, transcriptome, cloning, etc.), in order to unravel the mechanisms underlying refractoriness.

One of the hypothesis to explain resistance to therapy is that the kidney itself is not only a target for autoantibodies but also acts as a true lymphoid organ that hosts immunologically relevant processes resulting in further B-cell stimulation.

Facts and Figures

Project Lead
Prof. F Houssiau
Cliniques Universitaire Saint-Luc, Université catholique de Louvain
FOREUM research grant: € 298.860
2016 - 2019

Meet the Team

Prof. F Houssiau
Cliniques Universitaire Saint-Luc, Université catholique de Louvain
Prof. M Mahévas
Université Paris-Descartes
Prof. R van Vollenhoven
Karolinska Institutet
Prof. D Jayne
Adensbrooke's Hospital, University of Cambridge
Prof. R Cervera
Fundacio Clinic per a la Recerca Biomedica Barcelona
Dr. P Remy
Université Paris-Est
Mr. D Mazzoni
Lupus Europe

Patient Voice

We have involved Lupus Europe in the process as a patient partner organisation.

Interim Results

Lupus nephritis (LN) remains a severe complication of systemic lupus erythematosus, impacting long-term survival and quality of life.  Despite significant improvement in immunosuppressive drugs and regimens, at least 20% of LN patients still develop renal impairment, if not end-stage renal disease, requiring dialysis or renal transplantation.  The aim of this tissue-based project is to unravel the cellular and molecular mechanisms underlying renal injury in LN, in particular in cases not responding to standard of care immunosuppressive therapy, taking advantage of renal biopsy samples obtained within the frame of long-term clinical trials.


Pamfil C, Makowska Z, De Groof A, et al. Intrarenal activation of adaptive immune effectors is associated with tubular damage and impaired renal function in lupus nephritis. Annals of the Rheumatic Diseases Published Online First: 31 July 2018. doi: 10.1136/annrheumdis-2018-213485
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