A new model for autoantibody formation in systemic sclerosis
Grantee: Rasmus Iversen, Postdoc, Oslo University Hospital, Norway
Amount: DKK 3,966,274
Grant category: Research Grants in open competition
Year: 2024
Geography: Norway
Rasmus Iversen’s project explores the hypothesis that complex formation between self- and non-self-antigen can drive pathogenic T cell-B cell interactions and autoantibody formation in autoimmune diseases like Systemic Sclerosis (SSc). Inspired by previous work on celiac disease, Rasmus Iversen and his team will use the function of the B-cell antigen as a starting point to decipher disease mechanisms. In SSc, the T-cell antigen(s) are unknown, but there is disease-specific production of autoantibodies to centromere proteins (CENPs) with CENP-B being a major B-cell antigen. To investigate autoantibody formation, Rasmus Iversen and the team will isolate CENP-B-specific B cells from blood of SSc patients. In the first step (WP1), they will characterize the cells’ phenotypes in detail. The cells will then be used for generation of recombinant CENP-B-specific monoclonal antibodies (mAbs) in WP2. These mAbs will be used for studying interactions between the immune system, CENP-B and target DNA. In WP3, they aim to identify DNA fragments of commensal bacteria that can form complexes with CENP-B and potentially drive T cell-B cell interactions.
The results of Rasmus Iversen’s project may provide Insight into disease mechanisms and can potentially lead to discovery of new therapeutic targets in e.g. systemic sclerosis (SSc), which is a serious autoimmune disease that affects the skin and internal organs.