Abstract
Background: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm with inflammatory characteristics. This study aims to investigate the correlation between sCD25 levels and clinical characteristics and prognosis in pediatric LCH.
Procedure: Serum sCD25 levels were measured in 370 LCH patients under 18 years old using ELISA assays. The patients were divided into two cohorts based on different treatment regiments. We further assessed the predictive value for prognosis impact of sCD25 in a test cohort, which was validated in the independent validation cohort.
Results: The median serum sCD25 level at diagnosis was 3908 pg/ml (range: 231-44 000). sCD25 level was significantly higher in MS RO+ LCH patients compared to SS LCH patients (P <0.001). Patients with increased sCD25 were more likely have involvement of risk organs, skin, lung, lymph node, or pituitary (all P < 0.05). sCD25 level could predict LCH progression and relapse with an area under the ROC curve of 60.6%. The best cutoff value was determined at 2921 pg/ml. High-sCD25 group had a significantly worse progression-free survival than those in the low-sCD25 group (P< 0.05).
Conclusion: Elevated serum sCD25 levels at initial diagnosis was associated with high-risk clinical features and worse prognosis. sCD25 levels can predict the progression/recurrence of LCH after treatment with first-line chemotherapy.
Keywords: Langerhans cell histiocytosis, sCD25, prognosis, relapse
Introduction
Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder, which includes a broad range of clinical manifestations and outcomes, ranging from self-limited lesions to life-threatening disseminated disease1,2. Over the past decade, recurrent somatic activating gene mutations in mitogen-activated protein kinase (MAPK) pathway have been identified in approximately 85% of LCH lesions3,4. More research advances defined LCH as an inflammatory myeloid neoplasia with the extent of disease corresponding to the cell of origin in which activating mutations arise5. LCH lesions contain Langerhans cells (CD1a+/CD207+dendritic cells) along with a prominent inflammatory infiltrate of various immune cells (T cells, macrophages, eosinophils, neutrophils, and natural killer cells, et al.) that also contributes to aspects of pathogenesis6-8. These infiltrating cells produce large amounts of pro-inflammatory cytokines and chemokines, creating a lesional cytokine storm9,10. Several studies have shown that increased serum cytokine and chemokines, such as IL-6, IL-10, IL-18, TNF-α, et al., were associated with the disease extent or the mutation status in LCH11-13.
Soluble CD25 (sCD25), a soluble form of the α-subunit of interleukin-2 receptor (IL-2Rα), is generated exclusively by the proteolytic cleavage of the membrane-bound IL-2Rα, and its concentration is thought to reflect the immune activation during infection or inflammation14-17. Elevated serum sCD25 has been detected in autoimmune inflammatory diseases, cancers, and infectious disorders, and it has been used as a biomarker of disease progression and prognosis18-22. Several studies have observed that pre-treatment sCD25 was increased in LCH patients compared to healthy controls, and it significantly correlated with disease extent and survival of LCH23-25. However, the clinical relevance and prognostic impact of sCD25 have not been fully clarified in pediatric LCH. In the present study, we retrospectively evaluated the correlation between sCD25 levels and clinical-biological characteristics of pediatric LCH patients. We further assessed the predictive value for progression/relapse and prognosis impact of sCD25 in a test cohort, which was validated in the independent validation cohort.
MATERIALS AND METHODS