To assess serum levels of high mobility group box chromosomal protein 1 (HMGB‐1) and the soluble receptor for advanced glycation end products (sRAGE) in patients with Sjögren's syndrome (SS) and explore correlations with disease activity.

Thirty‐nine patients with SS and 21 healthy controls were included in this cross‐sectional study. Clinical and laboratory values were obtained from all patients. Disease activity was assessed using the European League Against Rheumatism SS Disease Activity Index (ESSDAI). Serum samples were collected and HMGB‐1 and sRAGE levels were measured using enzyme‐linked immunosorbent assay (ELISA), and HMGB‐1 concentrations were semiquantified by Western blotting.

In ELISA, HMGB‐1 serum levels did not differ between healthy controls and patients with SS (P = 0.783). When measured by semiquantitative Western blotting, HMGB‐1 levels were increased in patients with SS compared to healthy controls (P = 0.012). HMGB‐1 serum levels detected by Western blotting were higher in patients with extraglandular manifestations (P = 0.003) and were correlated with ESSDAI disease activity (r = 0.544, P < 0.0001). Furthermore, sRAGE was elevated in the sera of patients with SS (P = 0.003) compared to healthy controls and was also correlated with the ESSDAI (r = 0.545, P = 0.002).

Serum levels of total HMGB‐1 and sRAGE were elevated in patients with SS compared to healthy controls and correlated with disease activity as measured by the ESSDAI. Patients with extraglandular involvement had high serum levels of HMGB‐1.