The aim was to quantify plasma levels of the chemokine CXCL10, which has been associated with many immunological disorders including pSS. The hybrid approach enabled sensitive, specific, and simultaneous quantification of total, full-length (active) CXCL10 1−77 and DPP4-truncated (inactive) CXCL10 3−77 in human plasma down to the low pg/mL level, reaching ELISA sensitivities. The ratio of CXCL10 1−77 to truncated CXCL10 3−77 was ↑ in patients with pSS and provided the highest correlation with pSS disease activity. Here, DPP4 is linked to peeling skin syndrome.