• Yvonne Sundström, Ming-Mei Shang, Sudeepta Kumar Panda, Caroline Grönwall, Fredrik Wermeling, Iva Gunnarsson, Ingrid E Lundberg, Michael Sundström, Per-Johan Jakobsson, and Louise Berg.
• Division of Rheumatology, Department of Medicine Solna, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
• Transl Res. 2021 Mar 1; 229: 69-82.

AbstractB-cell secretion of autoantibodies drives autoimmune diseases, including systemic lupus erythematosus and idiopathic inflammatory myositis. Few therapies are presently available for treatment of these patients, often resulting in unsatisfactory effects and helping only some of the patients. We developed a screening assay for evaluation of novel targets suspending B-cell maturation into antibody secreting cells, which could contribute to future drug development. The assay was employed for testing 43 high quality chemical probes and compounds inhibiting under-explored protein targets, using primary cells from patients with autoimmune disease. Probes inhibiting bromodomain family proteins and histone methyl transferases demonstrated abrogation of B-cell functions to a degree comparable to a positive control, the JAK inhibitor tofacitinib. Inhibition of each target rendered a specific functional cell and potential disease modifying effect, indicating specific epigenetic protein targets as potential new intervention points for future drug discovery and development efforts.Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

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