When autoimmunity gets more than skin deep
Concept
SLE and many rheumatic autoimmune diseases are characterized by autoantibodies, which are produced when B cells derange and recognize self-tissue as foreign. This is referred to as tolerance breakthrough. The tolerance checkpoints regulating B cell activation and terminal plasma cell differentiation are ill defined and understood.
We aim to identify the immunological mechanisms underlying the breach of tolerance checkpoints that lead to autoantibody production. We will take a unique approach by studying tolerance checkpoints in the cutaneous B cell response in SLE compared to chronic cutaneous lupus erythematosus (CCLE). Most patients with CCLE have skin involvement and no autoantibodies, but some subsequently develop SLE with loss of tolerance and systemic B cell autoimmunity.
Thus, this approach provides an exceptional opportunity to delineate tolerance checkpoints at the local site where B cell activation and break of tolerance occurs.
Facts and Figures
Assistant professor, PhD Jolien Suurmond
Leiden University Medical Center
j.suurmond@lumc.nl
Meet the Team
Project Lead
Assistant professor, PhD Jolien SuurmondLeiden University Medical Center
j.suurmond@lumc.nl
NVLE
Patient Research Partner
NVLE (Dutch Patient Organization for lupus, APS, scleroderma en MCTD)
Patient Research Partner
Objectives
To define the tolerance checkpoints in the cutaneous B cell response and to identify the immunological mechanisms underlying the break of tolerance checkpoints in SLE.
The specific objectives are:
- Identify B cell tolerance checkpoints in the skin and its breakthrough in SLE
- Define which plasma cells in the skin originate from local precursor B cells
- Determine the mechanisms for plasma cell differentiation in the skin
Goals/Milestones
- M1: Building a clinical database for the study
- M2: Spectral flow cytometry assays to determine the frequency of autoreactive B cells.
- M3: Cultures of cutaneous B cells.
- M4: Imaging cytof.
- M5: scRNAseq data analysis.
Patient Voice
Patients will be recruited from the outpatient clinics of the LUMC department of dermatology or rheumatology. Based on the number of patients that are currently being seen at our clinic and recruitment rate for similar studies in recent years we expect that recruitment for this study should be possible within 24 months.
We have approached two patient representatives who agreed to help us writing our patient information sheets and communicating our results. Two patient representatives with skin lupus, one with and one without SLE agreed to help us with this study. They have been involved in writing the patient information form, and we will continue to discuss the results and next steps throughout the project. Besides this, we will also ask for advice from the patient council of our department, which consists of patients with different rheumatic diseases including SLE.