The sites at Arg97 and Arg163 are located within exposed regions as predicted by PoPS.39,41 The prediction of three C1s cleavage sites in HMGB1, a pro-inflammatory nuclear alarmin associated with SLE-like conditions,37 led us to examine whether C1s cleaves HMGB1 and inactivates its pro-inflammatory activities. This evidence concerns the gene HMGB1 and systemic lupus erythematosus.