Within the frame of this project, we aim to identify factors that contribute to or portend favourable or unfavourable response to biological therapy in SLE, with focus on B cell targeted therapies. 

We have shown that organ damage is associated with belimumab inefficacy in a Swedish real-life [1] and a clinical trial setting [2], with thrombotic events and neuropsychiatric damage mainly accounting for this association. In another study, we showed that positive titres of anti-Sm were a predictor of response to belimumab therapy [3]. Recently, we reported that levels of autoantibodies in immune complexes reflected clinical activity and portended response to belimumab better than free circulating autoantibody levels [4]. We did this by applying a novel technique for measuring autoantibody levels in immune complexes developed by Azita Sohrabian at Professor Johan Rönnelid’s laboratory facilities at the Uppsala University. In brief, C1q-bound immune complexes are eluted from C1q beads in two steps utilising 50 μL 0.1 M glycine-HCl (pH 2.5) and 100 μL 25% methanol (pH 11.5), as illustrated in the figure; the second step allows freeing of antibodies from corresponding antigens with preservation of antigen specificity. Levels of multiple autoantibodies against nuclear antigens in serum (free circulating) and in solubilised immune complexes were next determined using addressable laser bead immunoassay.