Pathogenesis of SLE

Break of immunological tolerance is at the basis of the development of autoimmunity and consequently autoimmune diseases. As the presence of disease-specific auto-antibody responses and the efficacy of B cell targeting therapies indicate a pivotal role for B cells in disease pathogenesis in several rheumatic diseases.

Aim and focus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease hallmarked by a plethora of autoantibodies, most prominently anti-nuclear antibodies (ANA). These autoantibodies are pathogenic and associate with severe clinical complications, including lupus nephritis. Autoantibodies are produced by plasma cells, the antibody producing cells. Plasma cells differentiate from activated precursor B cells and can be generated via several distinct differentiation pathways and cellular precursors. Although developments in recent years have led to increased understanding of B cell tolerance checkpoints for autoreactive B cells, there is a lack of understanding of the exact pathways leading to autoantibody production.

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Aim and focus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease hallmarked by a plethora of autoantibodies, most prominently anti-nuclear antibodies (ANA). These autoantibodies are pathogenic and associate with severe clinical complications, including lupus nephritis. Autoantibodies are produced by plasma cells, the antibody producing cells. Plasma cells differentiate from activated precursor B cells and can be generated via several distinct differentiation pathways and cellular precursors. Although developments in recent years have led to increased understanding of B cell tolerance checkpoints for autoreactive B cells, there is a lack of understanding of the exact pathways leading to autoantibody production.

By studying these pathways we aim to obtain in-depth insight into the cellular and molecular sources of pathogenic antibodies in SLE. The final goal is to identify different therapeutic targets to achieve quiescent disease without global immunosuppression. We believe these can be achieved by specific targeting of the causative pathways for autoantibody production.

We use high dimensional analysis methods, such as spectral flow cytometry and single cell RNA-sequencing, and serological studies, to uncover B cell activation and differentiation pathways.

projects

Themes for innovation / Societal Outreach

Key publications

Our Team members

  • Jolien Suurmond: group leader
  • Hugo van Dooren: PhD student
  • Sophie-Anne Smith: PhD student
  • Lars van Vliet: PhD student
  • Annemarie Dorjée: research technician
  • René Toes: head of the laboratory of experimental rheumatology