Das Institut für Experimentelle Endokrinologie – Forschung an hormoneller Regulation und Wirkung
Die Wirkungen von Hormone begleiten uns unser Leben lang. Sie steuern unsere körperliche und geistige Entwicklung, beeinflussen unser bewusstes und unbewusstes Verhalten und unterliegen in ihrer Wirkung einem steten Wandel durch alle unsere Lebensphasen. Die Endokrinologie als wissenschaftliches Fachgebiet beschäftigt sich im weitesten Sinne mit deren Auf- und Abbau, Transport und Wirkung.
Am Institut für Experimetelle Endokrinologie wird aktiv an unserem Verständnis und Wissen über diese Vorgänge geforscht. Hierbei liegt ein besonderer Schwerpunkt auf den Schilddrüsenhormonen und deren vielfältigen Wirkungen in unserem Organismus.
In verschiedenen Projekten, geleitet und koordiniert von einem Stab an engagierten und renommierten Wissenschaftlerinnen und Wissenschaftlern, werden hier Erkenntnisse gesammelt, die in Bereichen der Biologie, Medizin und Labordiagnostik praktische Anwendung finden.
Autoren:Chillon TS, Maares M, Demircan K, Hackler J, Sun Q, Heller RA, Diegmann J, Bachmann M, Moghaddam A, Haase H, Schomburg L.
Background: Zinc (Zn) is an essential trace element with high relevance for the immune system, and its deficiency is associated with elevated infection risk and severe disease course. The association of Zn status with the immune response to SARS-CoV-2 vaccination is unknown.
Methods: A cohort of adult health care workers (n=126) received two doses of BNT162B2, and provided up to four serum samples over a time course of 6 months. Total SARS-CoV-2 IgG and neutralizing antibody potency was determined, along with total as well as free Zn concentrations.
Results: The SARS-CoV-2 antibodies showed the expected rise in response to vaccination, and decreased toward the last sampling point, with highest levels measured three weeks after the second dose. Total serum Zn concentrations were relatively stable over time, and showed no significant association with SARS-CoV-2 antibodies. Baseline total serum Zn concentration and supplemental intake of Zn were both unrelated to the antibody response to SARS-CoV-2 vaccination. Time resolved analysis of free Zn indicated a similar dynamic as the humoral response. A positive correlation was observed between free Zn concentrations and both the induced antibodies and neutralizing antibody potency.
Conclusion: While the biomarkers of Zn status and supplemental Zn intake appeared unrelated to the humoral immune response to SARS-CoV-2 vaccination, the observed correlation of free Zn to the induced antibodies indicates a diagnostic value of this novel biomarker for the immune system.
Zeitschrift (Journal):Front Immunol. Jahr:2022; Jahrgang (Volume):13
Autoren:Demircan K, Sun Q, Bengtsson Y, Seemann P, Vallon-Christersson J, Malmberg M, Saal LH, Rydén L, Minich WB, Borg Å, Manjer J, Schomburg L.
Background: Low concentrations of serum selenium (Se) and its main transporter selenoprotein P (SELENOP) are associated with a poor prognosis following breast cancer diagnosis. Recently, natural autoantibodies (aAb) with antagonistic properties to SELENOP uptake have been identified in healthy subjects, and in patients with thyroid disease. Given the potential transport disrupting properties, we hypothesized that breast cancer patients with SELENOP-aAb may have a poor prognosis.
Methods: SELENOP-aAb along with serum Se, SELENOP and GPX3 activity were determined in serum samples of 1988 patients with a new diagnosis of breast cancer enrolled in the multicentre SCAN-B study. Patients were followed for ∼9 years and multivariate Cox regression models were applied to assess hazard ratios.
Results: Applying a cut-off based on outlier detection, we identified 7.65% of patients with SELENOP-aAb. Autoantibody titres correlated positively to total Se and SELENOP concentrations, but not to GPX3 activity, supporting a negative role of SELENOP-aAb on Se transport. SELENOP-aAb were associated with age, but independent of tumor characteristics. After fully adjusting for potential confounders, SELENOP-aAb were associated with higher recurrence, HR(95%CI) = 1.87(1.17-2.99), particularly in patients with low Se concentrations, HR(95%CI) = 2.16(1.20-3.88). Associations of SELENOP-aAb with recurrence and mortality were linear and dose-dependent, with fully adjusted HR(95%CI) per log increase of 1.25(1.01-1.55) and 1.31(1.13-1.51), respectively.
Conclusion: Our results indicate a prognostic and pathophysiological relevance of SELENOP-aAb in breast cancer, with potential relevance for other malignancies. Assessment of SELENOP-aAb at time of diagnosis identifies patients with a distinctly elevated risk for a poor prognosis, independent of established prognostic factors, who may respond favourably to Se supplementation.
Zeitschrift (Journal):Redox Biol Jahr:2022; Jahrgang (Volume):53
Autoren:Demircan K, Chillon TS, Sun Q, Heller RA, Klingenberg GJ, Hirschbil-Bremer IM, Seemann P, Diegmann J, Bachmann M, Moghaddam A, Schomburg L.
The essential trace element selenium (Se) is of central importance for human health and particularly for a regular functioning of the immune system. In the context of the current pandemic, Se deficiency in patients with COVID-19 correlated with disease severity and mortality risk. Selenium has been reported to be associated with the immune response following vaccination, but it is unknown whether this also applies to SARS-CoV-2 vaccines. In this observational study, adult health care workers (n = 126) who received two consecutive anti-SARS-CoV-2 vaccinations by BNT162b2 were followed for up to 24 weeks, with blood samples collected at the first and second dose and at three and 21 weeks after the second dose. Serum SARS-CoV-2 IgG titres, neutralising antibody potency, total Se and selenoprotein P concentrations, and glutathione peroxidase 3 activity were quantified. All three biomarkers of Se status were significantly correlated at all the time points, and participants who reported supplemental Se intake displayed higher Se concentrations. SARS-CoV-2 IgG titres and neutralising potency were highest three weeks after the second dose and decreased towards the last sampling point. The humoral immune response was not related to any of the three Se status biomarkers. Supplemental Se intake had no effect at any time point on the vaccination response as measured by serum SARS-CoV-2 IgG levels or neutralising potency. Overall, no association was found between Se status or supplemental Se intake and humoral immune response to COVID-19 mRNA vaccination.
Zeitschrift (Journal):Redox Biol. Jahr:2022; Jahrgang (Volume):50
Autoren:Chillon TS, Demircan K, Heller RA, Hirschbil-Bremer IM, Diegmann J, Bachmann M, Moghaddam A, Schomburg L.
Titel:Relationship between Vitamin D Status and Antibody Response to COVID-19 mRNA Vaccination in Healthy Adults
The immune response to vaccination with SARS-CoV-2 vaccines varies greatly from person to person. In addition to age, there is evidence that certain micronutrients influence the immune system, particularly vitamin D. Here, we analysed SARS-CoV-2 IgG and neutralisation potency along with 25-hydroxy-cholecalciferol [25(OH)D] concentrations in a cohort of healthy German adults from the time of vaccination over 24 weeks. Contrary to our expectations, no significant differences were found in the dynamic increase or decrease of SARS-CoV-2 IgG as a function of the 25(OH)D status. Furthermore, the response to the first or second vaccination, the maximum SARS-CoV-2 IgG concentrations achieved, and the decline in SARS-CoV-2 IgG concentrations over time were not related to 25(OH)D status. We conclude that the vaccination response, measured as SARS-CoV-2 IgG concentration, does not depend on 25(OH)D status in healthy adults with moderate vitamin D status.
Zeitschrift (Journal):Biomedicines Jahr:2021; Jahrgang (Volume):9Ausgabe (Issue):(11)
Autoren:Demircan K, Bengtsson Y, Sun Q, Brange A, Vallon-Christersson J, Rijntjes E, Malmberg M, Saal LH, Rydén L, Borg Å, Manjer J, Schomburg L.
Titel:Serum selenium, selenoprotein P and glutathione peroxidase 3 as predictors of mortality and recurrence following breast cancer diagnosis: A multicentre cohort study
Even though screening and personalized therapy led to a significant improvement of prognosis over the last years, breast cancer has still caused 685,000 deaths worldwide just in 2020 (WHO).
In this manuscript, we describe new biomarkers for identifying those patients at exceptionally high risk for all-cause mortality, and breast cancer recurrence. The composite biomarker outperformed classical prognostic markers such as Nottingham Histologic Grade, Lymph node involvement or tumour size, and improved the prognostic model.
Zeitschrift (Journal):Redox Biol. Jahr:2021; Jahrgang (Volume):47
Titel:Selenium Deficiency Due to Diet, Pregnancy, Severe Illness, or COVID-19—A Preventable Trigger for Autoimmune Disease
Zeitschrift (Journal):Int. J. Mol. Sci Jahr:2021; Jahrgang (Volume):22Ausgabe (Issue):(6)
Autoren:Wandt VK, Winkelbeiner N, Lossow K, Kopp JF, Schwarz M, Alker W, Nicolai MM, Simon L, Dietzel C, Hertel B, Pohl G, Ebert F, Schomburg L, Bornhorst J, Haase H, Kipp AP, Schwerdtle T
Zeitschrift (Journal):Redox Biol. Jahr:2021;
Autoren:Hackler J, Heller RA, Sun Q, Schwarzer M, Diegmann J, Bachmann M, Moghaddam A, Schomburg L.
Zeitschrift (Journal):Nutrients . Jahr:2021; Jahrgang (Volume):13Ausgabe (Issue):(6)
Autoren:Kryczyk-Kozioł J, Zagrodzki P, Prochownik E, Błażewska-Gruszczyk A, Słowiaczek M, Sun Q, Schomburg L, Ochab E, Bartyzel M.
Titel:Positive effects of selenium supplementation in women with newly diagnosed Hashimoto's thyroiditis in an area with low selenium status
Zeitschrift (Journal):Int J Clin Pract. Jahr:2021;
Autoren:Latifa S. Kazi Tani, Alexandra T. Gourlan, Nouria Dennouni-Medjati, Philippe Telouk, Majda Dali-Sahi, Yahia Harek, Qian Sun, Julian Hackler, Moussa Belhadj, Lutz Schomburg and Laurent Charlet
Zeitschrift (Journal):Front. Med. Jahr:2021;