Although speculative, since our data from the cooling study showed higher HMGB1 release in SSc patients and the in vitro study showed higher IP-10 release after HMGB1 stimulation, HMGB1 and/or IP-10 serum concentrations might be beneficial as an early biomarker for elevated oxidative stress/tissue damage in SSc patients which warrant intervention. Here, HMGB1 is linked to systemic sclerosis.