Candidate targets identified in RNAi B-cell activation screen sorted by availability of structural data.

The top ten candidate targets are suitable for structure-based drug repositioning screening. For 10 candidate targets (number 11 to 20) no structures were available and thus they could not be used for structure -based drug repositioning. Silencing of all listed candidate targets leads to strong the downregulation of CD70 and CD80 expressions in the B cell Namalwa cell line activated by the TLR9 agonist ODN2006 without causing cell death (column cell survival). A literature study links nearly all candidate targets to cancer (C) and some to autoimmune diseases (AD) or cancer of the immune system (CIS). Overall, there are many novel autoimmune candidate targets and KDR (VEGFR2) emerges as one very promising with 36 protein structures, potent decrease in expression of CD70 and CD80 following knock out of target in activated Namalwa cells without affecting cell viability and links to both cancer and auto-immunity.