ECE2023 Eposter Presentations Pituitary and Neuroendocrinology (234 abstracts)
Immune landscape of peripheral blood mononuclear cells in patients with Cushing’s syndrome and mild autonomous cortisol secretion
Ariane Bäuerle 1 , Hanna F Nowotny 1 , Natalie Doll 1 , Stephanie Zopp 1 , Elisabeth Nowak 1 , Frederick Vogel 1 , Adrian Gottschlich 2 , Thomas Marchant Seiter 1 , Nicole Reisch 1 , Simon Rothenfußer 2 , Kroiss Matthias 1 , Leah Braun 1 & Martin Reincke 1
1University Hospital LMU Munich, Department of Internal Medicine IV, Munich, Germany; 2University Hospital LMU Munich, Division of Clinical Pharmacology, Medicine IV, Munich, Germany
Background: Endogenous Cushing’s syndrome (CS) is associated with increased susceptibility to infections and mortality. Previously reported effects of hypercortisolism on immune function include a reduced CD4+/CD8+ ratio with a shift towards IL4+T helper cells (Th2), suppressed NK-cell cytotoxic activity as well as a low-grade inflammatory profile.
Aim: This cross-sectional single center study aims to compare immune phenotype in patients with overt CS, mild autonomous cortisol secretion (MACS), CS on long-term adrenostatic treatment (> 5 months, LAT) and healthy controls.
Methods: T- and NK-cell subsets from peripheral blood mononuclear cells (PBMCs) isolated by density gradient centrifugation were analyzed using multicolor flow cytometry in 20 overt CS, 15 MACS, 15 LAT patients and 63 age and sex matched healthy controls.
Results: We found a significant reduction of CD4+/CD8+ ratio in patients with overt CS (median 1.7, IQR 0.65) and LAT (median 1.61, IQR 0.89), compared to healthy controls (median 3.18, IQR 2.43), with a significant shift towards Th2 differentiation. In contrast, there was no significant reduction of CD4+/CD8+ ratio in MACS (median 2.47, IQR 1.4), while the shift towards Th2 differentiation was still significantly present. FoxP3+ regulatory T cells (Tregs) and the overall NK-cell count were significantly reduced in patients with overt CS, LAT and MACS (P<0.0001), compared to healthy controls, with upregulated CD56dimCD16bright NK-cells and CD107a expression. Patients with overt CS presented with a significant reduction of activating (P=0.0028) and inhibitory (P=0.0161) NK-cell receptors. Patients on LAT and patients with MACS were found to have reduced NKp46 expression (P<0.0001) with no significant change in inhibitory NK-cell receptors, overall outweighing the presence of activating NK-cell receptors.
Conclusion: Altered CD4+/CD8+ ratios in patients with overt CS and LAT suggest a higher susceptibility to opportunistic and viral infections. The suppression of Tregs implies a chronic inflammatory state in all patient subgroups. Upregulation of cytotoxic NK-cell subsets may be a compensatory mechanism to suppression of activating NK-cell receptors. Changes in immunophenotype found in patients with MACS indicate less pronounced alterations compared to overt CS. Immunophenotype of patients with CS appears to be unchanged by LAT.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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