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Circulating immune profiles in ACTH-dependent Cushing's syndrome
Jie Liu1,2, Xiang Zhou2,3, Huijuan Zhu2,3
1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
Insights
ACTH-dependent Cushing's syndrome causes immune dysfunction and infection. This study differentiated Cushing's disease (CD) from ectopic ACTH syndrome (EAS) using immune profiling and predicted infection risk, showing immune recovery post-surgery.
Area of Science:
- Endocrinology
- Immunology
- Medical Diagnostics
Background:
- ACTH-dependent Cushing's syndrome (CS) is linked to significant immune impairment and increased susceptibility to severe infections.
- Differentiating between Cushing's disease (CD) and ectopic ACTH syndrome (EAS) is crucial for appropriate management.
- Understanding immune cell dynamics and recovery post-treatment is essential for patient outcomes.
Purpose of the Study:
- To characterize immune cell phenotypes in ACTH-dependent CS.
- To develop predictive models for distinguishing CD from EAS and assessing infection risk.
- To evaluate immune system recovery following successful surgical remission.
Main Methods:
- A retrospective single-center study included 211 patients with ACTH-dependent CS (173 CD, 38 EAS).
- Flow cytometry analyzed lymphocyte subsets; severe infection incidence was recorded.
- Machine learning models were developed for disease differentiation and infection risk prediction.
Main Results:
- Ectopic ACTH syndrome (EAS) patients exhibited more severe immune suppression than Cushing's disease (CD) patients, with lower CD4+ T cells and CD3+ T cells, and a higher percentage of CD19+ B cells.
- A machine learning model integrating immune and non-immune parameters achieved 75.4% accuracy in differentiating CD from EAS.
- A multivariate model predicted severe infection risk with an AUC of 0.851, incorporating 24h UFC, serum potassium, CD19+ B cell percentage, and CD4+ T cell count.
- Following surgical remission, significant T cell reconstitution was observed within 8 weeks, with a threefold increase in CD4+ T cells.
Conclusions:
- Immune cell profiling effectively distinguishes between CD and EAS in ACTH-dependent CS.
- Predictive models incorporating specific clinical and immunological parameters can identify patients at high risk for severe infections.
- Surgical remission of ACTH-dependent CS promotes substantial immune reconstitution, particularly in T cell populations.
Objective:
ACTH-dependent Cushing's syndrome (CS) causes profound immune dysfunction and severe infections. This study aimed to characterize immune cell phenotypes, develop predictive models for differentiating Cushing's disease (CD) from ectopic ACTH syndrome (EAS) and predict infection risk, and evaluate immune recovery after surgical remission.
Design:
Retrospective single-center study.
Methods:
We studied 211 patients with ACTH-dependent CS (173 CD, 38 EAS) aged 11-75 years. Twelve patients were evaluated longitudinally after remission. Lymphocyte subsets were analysed by flow cytometry, severe infection incidence was documented, and machine learning models were developed for disease differentiation.
Results:
EAS patients showed more severe immune suppression than CD, with reduced CD4+ T cells (224 [158.0-390.0] vs. 442 [313.0-611.0] cells/μL, P < .001) and CD3+ T cells (505 [342.0-815.0] vs. 930 [713.0-1246.0] cells/μL, P < .001), while elevated percentage of CD19+ B cells (18.2% [13.3%-25.5%] vs. 9.6% [6.1%-14.4%], P < .001). Machine learning-based model integrating immune and non-immune parameters achieved improved balanced accuracy of 75.4% (AUC = .840, 95% CI: 0.770-0.910) for CD/EAS differentiation. Severe infections occurred in 13.7% of patients. The multivariate model incorporating 24 h UFC, serum potassium nadir, CD19+ B cell percentage, and CD4+ T cell count predicted severe infection risk (AUC = .851, 95% CI: 0.774-0.927; sensitivity 86.2%, specificity 68.7%). Following surgical remission, profound T cell reconstitution occurred after 8 weeks, with CD4+ T cells increasing 3-fold (P < .001).
Conclusions:
Immune profiling distinguishes CD/EAS and predicts infection risk in ACTH-dependent CS. Surgical remission facilitates immune reconstitution.
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