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