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. Here, C1S is linked to systemic lupus erythematosus.