Tailoring patient selection for biological therapy

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, wshowed 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. 


  1. Parodis I,Sjöwall C, Jönsen A, Ramsköld D, Zickert A, Frodlund M, Sohrabian A, Arnaud L, Rönnelid J, Malmström V, Bengtsson AA, Gunnarsson I. Smoking and pre-existing organ damage reduce the efficacy of belimumab in systemic lupus erythematosus. Autoimmunity Reviews. 2017; 16: 343–351

    Link: https://pubmed.ncbi.nlm.nih.gov/28216072/  


  1. Parodis I, Gomez A,Emamikia S, Chatzidionysiou K. Established organ damage reduces belimumab efficacy in systemic lupus erythematosus. Annals of the Rheumatic Diseases. 2019; 78(7): 1006–1007

    Link: https://pubmed.ncbi.nlm.nih.gov/30610063/  


  1. Parodis I,Åkerström E, Sjöwall C, Sohrabian A, Jönsen A, Gomez A, Frodlund M, Zickert A, Bengtsson AA, Rönnelid J, Gunnarsson I. Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus. International Journal of Molecular Sciences. 2020 May 14;21(10)

    Link: https://pubmed.ncbi.nlm.nih.gov/32422945/  


  1. SohrabianA, Parodis I, Carlströmer-Berthén N, Frodlund M, Jönsen A, Zickert A, Sjöwall C, Bengtsson AA, Gunnarsson I, Rönnelid J. Increased levels of anti-dsDNA antibodies in immune complexes before treatment with belimumab associate with clinical response in patients with systemic lupus erythematosus. Arthritis Research and Therapy. 2019 Nov 29;21:259 Contributed equally

    Link: https://pubmed.ncbi.nlm.nih.gov/31783909/