Caroline Grönwall

Autoreactive B cell and antibodies are central in the pathogenesis of rheumatic autoimmune diseases. Distinct autoantibody specificities are the hallmarks of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and idiopathic inflammatory myopathies (myositis). Yet, the autoreactivity is complex and heterogeneous and we still have limited knowledge about what drives the development of autoreactive B cells and how autoantibodies contribute to distinct tissue damage and inflammation. RA is characterized by anti-citrullinated protein autoantibodies (ACPA) and our recent single-cell studies have demonstrated that patient-derived ACPA have unexpected features. They have Fab N-glycosylations, high somatic hypermutations, and multi-reactivity to citrullinated targets, reflecting unusual B-cell processes. Interestingly, some ACPA clones promote pain and bone loss, but some have potent anti-inflammatory properties in murine arthritis. Our clonality data can now be translated into clinical assays for improved patient stratification. In this program I will use an interdisciplinary B-cell pipeline, patient immunomonitoring, and single-cell technology for studies of autoreactive B cells and patient-derived monoclonal autoantibodies. We will obtain in-depth data on the clonal epitope recognition in several diseases and patient subsets. Hereby we will increase the knowledge of fundamental processes in rheumatic disease and contribute to advancing personalized treatment.