The project validated novel assays for autoantigen monitoring in SLE patients in relation to treatment and clinical response. As such the researchers were able to combine autoantigen monitoring with autoantibody monitoring in SLE patients that were treated with RTX, RTX+BLM and BTZ, novel B-cell targeted strategies that differentially target B cell and plasma cell subsets. In a reverse translational study, it was demonstrated that autoantibody levels decreased upon each treatment strategy, but the extent of targeted autoantibodies was most significant for RTX+BLM in a quantitative manner (reduced autoantibody repertoire) as well as a qualitative manner (reduced low, medium and highavidity anti-dsDNA autoantibodies). These effects were less pronounced for RTX only and not observed in BTZ-treated patients. Especially the reversal of anti-C1q to seronegative was associated with reduced IC-mediated inflammation and clinical disease activity, which happened most frequent after RTX+BLM, less after RTX and not after BTZ treatment. Lastly, hints of persisting
autoreactive memory in SLE patients were found despite a clinical response to B-cell targeted therapy. These observations collectively demonstrated the relevance of in-depth monitoring of the immunological effects of B-cell targeted strategies that have potential implications for the clinic.