The development of an accurate clinical assessment tool for adverse drug reaction severity based on blood serum biomarkers could lead to safer and more effective medical treatments. Osteopontin (OPN) is one such promising inflammation biomarker found in a patient’s blood. Originally described as a protein involved in bone metabolism, OPN serum levels also play a significant role in immune pathways, including cancer mediation and several types of severe adverse drug reactions that manifest on the skin.
A collaborative team of medical researchers at Japan’s Showa University and Yokohama City University led by Marie Suzuki (2022) has reported on the role of OPN as a serum biomarker in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), and erythema multiforme-type drug reaction (EM-DR). The work featured in the Journal of Dermatology measured OPN serum levels in thirty-one patients across these three experimental conditions in addition to twenty healthy control patients. They used Arbor Assays DetectX® Human Osteopontin ELISA Kit (K021-H1) to quantify and compare OPN readings. Serum from patients suffering a severe cutaneous adverse drug reaction was measured either before or after treatment with prednisolone (PSL). Mann-Whitney U and Kruskal-Wallis tests were used for statistical analysis and Spearman’s test was used to assess the correlation of DIHS/DRESS cases with the DIHS/DRESS severity (DDS) score.
The results showed that the serum osteopontin levels of DIHS/DRESS patients and SJS/TEN patients were significantly higher than in controls. While the pairwise Mann–Whitney U tests indicated the OPN levels in DIHS/DRESS and SJS/TEN patients were higher than in EM-DR patients, the Kruskal–Wallis assessment used to compare all three groups was not significant. The team found that in patients treated with PSL for DIHS/DRESS, the level of OPN decreased to that of controls. However, no correlation was found between the (DDS) score and OPN levels.
Dual immunoassay labeling techniques were used on patient biopsies to assess the source of OPN measured. These tests confirmed that OPN was expressed in the nuclei of keratinocytes and most inflammatory cell infiltrates, including CD8+, CD4+, and CD68+ immune cells. There was no significant difference among the DIHS/DRESS, SJS/TEN, and EM-DR biopsy samples, however, DIHS/DRESS samples contained more OPN expressing CD8+ cells/field than EM-DR samples.
The findings suggest that OPN can be used as a primary blood serum biomarker for evaluating the severity of inflammation in patients experiencing drug-induced reactions, but further studies are needed to confirm its clinical utility and compatibility with DDS scoring. Accurate diagnosis and early intervention are crucial for the successful mitigation of cutaneous adverse drug reactions. The current lack of biomarkers for early diagnosis underscores the importance of exploring potential biomarkers such as OPN.