ECE2023 Poster Presentations Adrenal and Cardiovascular Endocrinology (72 abstracts)
Immunophenotypic differences in patients with primary adrenal insufficiency of different etiology
Hanna F. Nowotny 1 , Thomas Marchant Seiter 1 , Jing Ju 1 , Adrian Gottschlich 2 , Holger Schneider 1 , Stephanie Zopp 1 , Frederick Vogel 1 , Lea Tschaidse 1 , Matthias Auer 1 , Christian Lottspeich 1 , Sebastian Kobold 2,3,4 , Simon Rothenfußer 2 , Felix Beuschlein 1,5 , Martin Reincke 1 , Leah Braun 1 & Nicole Reisch 1
1LMU Klinikum, Medizinische Klinik and Poliklinik IV, Division of Endocrinology, Munich, Germany; 2LMU Klinikum, Medizinische Klinik and Poliklinik IV, Division of Clinical Pharmacology, Munich, Germany; 3German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany; 4Helmholtz Munich, Research Center for Environmental Health (HMGU), Einheit für Klinische Pharmakologie (EKLiP), Neuherberg, Germany; 5Universitätsspital Zürich (USZ) und Universität Zürich (UZH), Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Zurich, Switzerland
Background: Primary adrenal insufficiency (PAI) has been associated with increased risk of infection, adrenal crises and a higher mortality rate. This is caused by altered circadian cortisol profiles, which ultimately lead to immune cell dysregulation. In this study, we aim to characterize differences in immunophenotype of PAI patients of three different etiologies.
Methods: Cross-sectional single center study including 28 patients with congenital adrenal hyperplasia (CAH), 27 patients after bilateral adrenalectomy due to Cushing’s syndrome (BADx), 21 patients with Addison’s disease (AD) – all substituted with a stable daily median dose of 25 mg hydrocortisone (IQR 5 mg for BADx and AD and IQR 10 mg for CAH) – and 52 healthy controls. Peripheral blood mononuclear cells were isolated and used for analysis of immune cell subsets using multicolor flow cytometry after four-hour stimulation with phorbol myristate acetate (PMA)/Ionomycin, as well as a K562 based natural killer (NK-) cell cytotoxicity assay and qPCR analysis of clock gene expression.
Results: The percentage of IFNγ-secreting T helper (Th1) in AD (P=0.0024) and cytotoxic (Tc1) cells in CAH (P=0.0055) and AD patients (P=0.0075) was significantly reduced compared to controls. We additionally observed a downregulation of the percentage of IL-4+ Th2 cells in AD patients (P=0.0157) and Tc2 cells in AD (P=0.0154) and CAH patients (P=0.0012) compared controls. IL-17 producing T-cells were also downregulated in patients with AD compared to the other patient groups and controls (P<0.0001). NK-cell cytotoxicity (NKCC) was reduced in all subsets of PAI patients compared to controls with the smallest change in patients with CAH (mean specific lysis 57.5% in controls, 21.7% in CAH, -0.5% in AD and -28.7 in BADx). Activated NK-cell percentages were upregulated in BADx (P=0.0008) and AD patients (P=0.0348) compared to controls, also expressed as an increase in degranulation marker CD107a expression (BADx P<0.0001; AD P=0.0002). In contrast to NK-cell activating receptors, expression percentage of NK-cell inhibiting receptor CD94 was upregulated in both BADx and AD patients (P<0.0001).
Conclusion: This study presents novel data on immunophenotypic differences in subsets of PAI of differential etiology. Further analysis of potential influencing factors of immune regulation is necessary to determine the impact of imprinting effects of long-term GC excess and effects of elevated glucocorticoid and androgen precursors or 11oxC19 concentrations.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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