Elevated serum osteopontin levels in patients with severe cutaneous adverse drug reactions

Abstract

Osteopontin (OPN) was initially described as a protein involved in bone metabolism, but the roles played by OPN in the immune system and allergic reactions have attracted increasing attention. Here, we clarify the OPN‐related dynamics of severe cutaneous adverse drug reactions, and assess whether the OPN level has utility for classifying such reactions and serving as a biomarker of severity. Serum OPN levels in patients with drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and erythema multiforme‐type drug reaction (EM‐DR) were quantified by ELISA. The OPN sources were analyzed by dual immunofluorescence assay of DIHS, SJS/TEN and EM‐DR biopsy specimens. The serum OPN levels of DIHS/DRESS patients (489.1 ± 37.0 ng/mL) and SJS/TEN patients (508.5 ± 47.8 ng/mL) were significantly higher compared with controls (314.4 ± 14.3 ng/mL; p < 0.001). After treatment, the serum OPN level of DIHS/DRESS patients decreased to that of controls. In addition, OPN levels in DIHS/DRESS patients and SJS/TEN patients were higher than in patients with EM‐DR (Mann–Whitney U test, p < 0.05). However, when the Kruskal–Wallis test was used to compare the OPN levels among the three groups of patients, the difference was not significant (p = 0.055). Dual immunofluorescence assay revealed that T lymphocytes and macrophages were the main OPN sources in DIHS, SJS/TEN and EM‐DR patients. These data suggest that the OPN level can be used to evaluate the severity of inflammation in patients experiencing drug reactions.