Ali Kabli, Ahmed Bamaga, Raed Gasemaltayeb, Mohammed Karami, Alaa Alkhotani, Majid Almansouri, Hussain Noorwali, Motaz Fadul, Adnan Badahdah, Riffat Mehboob, Abdulaziz Alqarni, Khalid Khashoggi, Amal Alkhotani, Amany Fathaddin, Amber Hassan, Humaira Waseem, Maher Kurdi
Elevated muscle 11 -HSD1 expression before glucocorticoid therapy was associated with an improved clinical response after therapy in IMs. These findings support the potential role of 11 -HSD1 as a predictive biomarker.
INTRODUCTION: Glucocorticoid therapy is commonly used in inflammatory myopathies (IMs); however, patients' responses are variable, and predictive biomarkers remain unavailable. 11 -hydroxysteroid dehydrogenase type 1 (11 -HSD1), a key enzyme regulating intracellular glucocorticoid activation, may influence treatment response. This study evaluated the relationship between muscle 11 -HSD1 expression and clinical response to glucocorticoid therapy.
MATERIAL AND METHODS: This study included 32 patients with biopsy-confirmed IMs, of whom 25 received post-biopsy prednisolone (0.5-1 mg/kg/day) for approximately 8 months without glucocorticoid-sparing agents. Clinical response was evaluated based on muscle strength, symptom improvement, and creatinine kinase (CK) reduction. Muscle 11 -HSD1 expression was assessed and categorized as low-medium or high. Associations between enzyme expression and response to glucocorticoid were analyzed. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of 11 -HSD1 expression.
RESULTS: Among the 25 treated patients with glucocorticoid therapy, 21 (84.0%) demonstrated clinical improvement, while 4 (16.0%) showed no clinical response. Baseline diagnostic subtypes and MHC class I expression were not significantly associated with treatment outcome (p = 0.37 and p = 0.59, respectively). In contrast, high 11 -HSD1 expression was significantly associated with clinical improvement (66.7% vs. 0% in non-responders; p = 0.026). High 11 -HSD1 expression was associated with increased odds of response (OR = 17.4, 95% CI: 0.77-392). ROC analysis demonstrated good predictive performance (AUC = 0.83).
CONCLUSIONS: Elevated muscle 11 -HSD1 expression before glucocorticoid therapy was associated with an improved clinical response after therapy in IMs. These findings support the potential role of 11 -HSD1 as a predictive biomarker.