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Nowotny, H.F.* ; Marchant Seiter, T.* ; Ju, J.* ; Gottschlich, A.* ; Schneider, H.* ; Zopp, S.* ; Vogel, F.* ; Tschaidse, L.* ; Auer, M.K.* ; Lottspeich, C.* ; Kobold, S. ; Rothenfußer, S. ; Beuschlein, F.* ; Reincke, M.* ; Braun, L.* ; Reisch, N.*

Major immunophenotypic abnormalities in patients with primary adrenal insufficiency of different etiology.

Front. Immunol. 14:1275828 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
INTRODUCTION: Patients with primary adrenal insufficiency (PAI) suffer from increased risk of infection, adrenal crises and have a higher mortality rate. Such dismal outcomes have been inferred to immune cell dysregulation because of unphysiological cortisol replacement. As the immune landscape of patients with different types of PAI has not been systematically explored, we set out to immunophenotype PAI patients with different causes of glucocorticoid (GC) deficiency. METHODS: This cross-sectional single center study includes 28 patients with congenital adrenal hyperplasia (CAH), 27 after bilateral adrenalectomy due to Cushing's syndrome (BADx), 21 with Addison's disease (AD) and 52 healthy controls. All patients with PAI were on a stable GC replacement regimen with a median dose of 25 mg hydrocortisone per day. Peripheral blood mononuclear cells were isolated from heparinized blood samples. Immune cell subsets were analyzed using multicolor flow cytometry after four-hour stimulation with phorbol myristate acetate and ionomycin. Natural killer (NK-) cell cytotoxicity and clock gene expression were investigated. RESULTS: The percentage of T helper cell subsets was downregulated in AD patients (Th1 p = 0.0024, Th2 p = 0.0157, Th17 p < 0.0001) compared to controls. Cytotoxic T cell subsets were reduced in AD (Tc1 p = 0.0075, Tc2 p = 0.0154) and CAH patients (Tc1 p = 0.0055, Tc2 p = 0.0012) compared to controls. NKCC was reduced in all subsets of PAI patients, with smallest changes in CAH. Degranulation marker CD107a expression was upregulated in BADx and AD, not in CAH patients compared to controls (BADx p < 0.0001; AD p = 0.0002). In contrast to NK cell activating receptors, NK cell inhibiting receptor CD94 was upregulated in BADx and AD, but not in CAH patients (p < 0.0001). Although modulation in clock gene expression could be confirmed in our patient subgroups, major interindividual-intergroup dissimilarities were not detected. DISCUSSION: In patients with different etiologies of PAI, distinct differences in T and NK cell-phenotypes became apparent despite the use of same GC preparation and dose. Our results highlight unsuspected differences in immune cell composition and function in PAI patients of different causes and suggest disease-specific alterations that might necessitate disease-specific treatment.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Acth ; Addison’s Disease ; Bilateral Adrenalectomy ; Congenital Adrenal Hyperplasia ; Cortisol ; Immunophenotype ; Primary Adrenal Insufficiency; Killer-cell Function; Regulatory T-cells; Cushings-syndrome; Addisons-disease; Mortality; Autoimmune; Therapy; Hydrocortisone; Epidemiology; Hyperplasia
ISSN (print) / ISBN 1664-3224
e-ISSN 1664-3224
Zeitschrift Frontiers in Immunology
Quellenangaben Band: 14, Heft: , Seiten: , Artikelnummer: 1275828 Supplement: ,
Verlag Frontiers
Verlagsort Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Unit for Clinical Pharmacology (KKG-EKLiP)
Förderungen Eva Luise und Horst Kohler Stiftung & Else Kroner-Fresenius-Stiftung
Forderprogramm fur Forschung und Lehre (FoFoLe)
FoFoLe
Bavarian Cancer Research Center (BZKF)
DFG
Elite Network of Bavaria
Melanoma Research Alliance
Marie Sklodowska-Curie Training Network for the Immunotherapy of Cancer (IMMUTRAIN) (Horizon 2020 programme of the European Union)
Marie Sklodowska-Curie Training Network for Optimizing Adoptive T Cell Therapy of Cancer (Horizon 2020 programme of the European Union)
Else Kroner-Fresenius-Stiftung
German Cancer Aid
Wilhelm-Sander-Stiftung
Deutsche Forschungsgemeinschaft (DFG)
Ernst Jung Stiftung
Institutional Strategy LMUexcellent of LMU Munich
Go-Bio-Initiative
Bavarian Ministry for Economical Affairs
Bundesministerium fur Bildung und Forschung
European Research Council
Fritz-Bender Foundation
Deutsche Jose Carreras Leukamie Stiftung
Bayerische Forschungsstiftung (BAYCELLator)
Hector Foundation