Clinical Research Unit 296 ‘Feto-maternal immune cross talk’
During pregnancy, the maternal immune system develops immunological tolerance to the fetus. This immunological tolerance arises from the intense dialogue of pregnancy hormones and immune cells and contributes to a complication-free course of pregnancy until the birth of the child. Significant benefits to the health of the mother are associated with mounting immunological tolerance, such as a mitigation of maternal autoimmune diseases. On the other hand, pregnant women are at a significant health disadvantage because they have a high susceptibility to infection, for example towards the influenza virus.
Challenges during pregnancy, such as infections, but also maternal stress and use of medication, may confer disadvantages to children's health later in life.
In the Clinical Research Unit 296, which is represented by Petra Arck as a speaker, includes physicians and basic researchers from a variety of medical disciplines, aims to understand the mechanisms underlying the health advantages and disadvantages for mother and child originating during pregnancy.
For more information visit the following UKE website: KFO 296
This network is funded by the German Research Foundation (Deutsche Forschungsgemeinschaft) Visit: https://gepris.dfg.de/gepris/projekt/255154572
The PRINCE Study (PRenatal IdeNtification of Children’s HEalth) is a prospective longitudinal pregnancy cohort study which commenced in 2011 at the University Medical Center Hamburg.
It is one of the most comprehensive cohorts of healthy pregnant women in Europe. The current number of mother-child pairs is 750. Pregnant PRINCE participants are seen three times during pregnancy, at the end of the first trimetser of pregnancy (gestation week 12-14), the second trimester (week 24) and the third trimester (week 34. At each study visit, ultrasound is performed and a maternal venous blood sample is taken. Pregnancy progression, health status and weight gain of the mother are documented, along with nutrition, stress perception, use of medication or infections. Pregnancy complications – if occuring - are recorded and immidiately treated. The health and early life environment of the babies born in the PRINCE study is documented using questionnaires, sent between the age of six month to four years. Queries include the use of childhood vaccination and the incidence of infections. At the age of five and ten years, the children participate in an on-site visit, where a physical examination is performed, blood is taken and lung function and neurocognitive performance are tested.
The aim of the PRINCE Study is to understand how children ‘s health is determined before birth – or how childhood diseases may be programmed very early.
Add-on studies to the PRINCE Study, in which healthy pregnant women are included, have ben initiated. These include the PRINCE_Covid Study, in which pregnant women suffering from COVID-19 have been recruited. Additonally, women vaccinated during pregnancy, i.e. with the Corona vaccine, are enrolled in the PRINCE-Vaccine Study. Furthermore, the PRINCE-Breast Study has just started. Here, women diagnosed with breats cancer during pregnancy are included.
The PRINCE Studies have been conceptionalized, initiated and are supervised by Anke Diemert, a certified OB/GYN specialist and Professor of Midwifery, and Petra Arck, Professor for Experimental Feto-Maternal Medicine.
If you are pregnant, live in or near Hamburg and interested in participating the study, please visit our German PRINCE website
Specialist in Obstetrics and Gynecology
Pregnancy-induced maternal microchimerism
shapes neurodevelopment and behavior
Schepanski S, Chini M, Sternemann V, Urbschat C, Thiele K, Sun T, Zhao Y, Poburski M, Woestemeier A, Thieme MT, Zazara DE, Alawi M, Fischer N, Heeren J, Vladimirov N, Woehler A, Puelles VG, Bonn S, Gagliani N, Hanganu-Opatz IL, Arck PC. Pregnancy-induced maternal microchimerism shapes neurodevelopment and behavior in mice.
Nat Commun. 2022 Aug 5;13(1):4571. doi: 10.1038/s41467-022-32230-2. PMID: 35931682; PMCID: PMC9356013.
Emergence of immune memory and tissue resident immunity during reproduction
A successful pregnancy is associated with a significantly reduced risk of complications in subsequent pregnancies. Biological processes that contribute to this reduced risk of pregnancy complications are currently unknown. In the present project, we aim to identify immune markers through which this reduced risk of complications in subsequent pregnancies is mediated. We expect that the findings from the proposed project will allow us to form a solid basis for the development of diagnostic markers and therapeutic approaches, with the aim of improving the chances of a healthy (first) pregnancy.
This project is funded by the German Research Foundation (Deutsche Forschungsgemeinschaft)
Long-term programming of sex differences in immunity by prenatal exposure to stress
Prenatal adverse environments including the exposure to stress adversely program immunity later in life. Hereby, significant sex differences in childhood- and adult-onset immune disorders have been observed, which can perpetuate or reverse instinctive sex-specific immune responses. We here investigate how fetal exposure to prenatal glucocorticoid surges differentially modulates long-term immunity later in life of male and female offspring. We will provide insights on the degree of control of viral infections and tumor growth in male and female offspring challenged by an adverse prenatal environment.
If you want to learn more about the project: Visit their website
This project is embedded into the Research Unit 5068 ‘Sex differences in immunity’ and funded by the German Research Foundation (Deutsche Forschungsgemeinschaft)
Reducing the infection risk in children: understanding the trajectories of maternal and childhood vaccinations (REINFORCE):
The risk for childhood infections is greatly dependent on the complex interaction between maternal levels of antibodies during pregnancy, the order and response to childhood vaccinations, the sex of the child and the environment. In the present proposal, we seek to establish an international collaboration between experts in the field of early life infections based in Copenhagen and Hamburg in order to evaluate the trajectories of maternal and child vaccinations and early life infections in Norther European countries.
This network is funded by the Authority for Science, Research and Equality, Hamburg, Germany within the program to promote collaboration among research institutions located near the Baltic Sea
Research Network FV73 ‘Pregnancy, immunity and health risks in mother and child’
Pregnancy can be considered as a blueprint for understanding the immune response to infections and neuro-immunological cross talk. This research network expands is coordinated by Petra Arck as a speaker and links the repertoire of diseases addressed in the CRU 296.
In individual subprojects, we here investigate the pathogenesis of severe malaria during pregnancy, the long-term consequences of pre-eclampsia for mother and child, immune-metabolic trajectories of pregnancy and how maternal immune cells affect immunity and neurocognition in offspring. Further, we develop organoids relevant to understand feto-maternal immune cross talk as well as tools to improve data management and sharing.
This network is funded by the Authority for Science, Research and Equality, Hamburg, Germany (LFF-FV73)
Next Generation Partnerships – Thematische Netzwerke
Prediction of preterm birth - prevention of inequality among children
Each year, approx. 15 million babies worldwide are born prematurely, before gestation week 37. These children have an increased risk to die during their first year of life and to develop health problems. These include a greater susceptibility for infections, allergies, asthma and also poorer neurocognitive performances. In adult life, being born too soon can also affect the ability to work, which further aggravates the inequalities resulting from prematurity.
Despite continuous progress made in the field of preventive medicine over the last decades, the options to predict preterm birth are still very poor. Therefore, it is the goal of our project to characterize biological signatures that are predictive for preterm birth at a time point during pregnancies when no risk can be foreseen. Such knowledge will then inform future prenatal care and allows to identify pregnancies at risk for preterm birth by clinical routine screening.
Our network comprises of partners located at the Medical Faculty of the Universität Hamburg, at the University of Groningen, NL as well as at Stanford University and University of California San Diego, USA, which allows us to address the research question in a translational approach, combined with -omics technology-derived data and machine learning-based predictive modeling.
PRINCE: PRenatal IdeNtification of Children’s HEalth Study
Tissue‑resident immunity in the female and male reproductive tract
Yüzen D, Arck PC, Thiele K. Tissue-resident immunity in the female and male reproductive tract.
Semin Immunopathol. 2022 Apr 29:1–15. doi: 10.1007/s00281-022-00934-8. Epub ahead of print. PMID: 35488095; PMCID: PMC9053558.
Infant immunity against viral infections is advanced by theplacenta-dependent vertical transfer of maternal antibodies
Albrecht M, Pagenkemper M, Wiessner C, Spohn M, Lütgehetmann M, Jacobsen H, Gabriel G, Zazara DE, Haertel C, Hecher K, Diemert A, Arck PC. Infant immunity against viral infections is advanced by the placenta-dependent vertical transfer of maternal antibodies.
Vaccine. 2022 Mar 8;40(11):1563-1571. doi: 10.1016/j.vaccine.2020.12.049.
Epub 2021 Jan 9. PMID: 33431223.
A prenatally disrupted airway epithelium orchestrates the fetal origin of asthma in mice
Zazara DE, Wegmann M, Giannou AD, Hierweger AM, Alawi M, Thiele K, Huber S, Pincus M, Muntau AC, Solano ME, Arck PC. 2020 Jun; 145(6):1641-1654. doi: 10.1016/j.jaci.2020.01.050. Epub 2020 Apr 15. PMID: 32305348.
Vertically transferred maternal immune cells
promote neonatal immunity against early life infections
Stelzer IA, Urbschat C, Schepanski S, Thiele K, Triviai I, Wieczorek A, Alawi M, Ohnezeit D, Kottlau J, Huang J, Fischer N, Mittrücker HW, Solano ME, Fehse B,
Nat Commun. 2021 Aug
4;12(1):4706. doi: 10.1038/s41467-021-24719-z. PMID: 34349112; PMCID:
Inefficient Placental Virus Replication and Absence of Neonatal Cell-Specific Immunity Upon Sars-CoV-2
Infection During Pregnancy
Tallarek AC, Urbschat C, Fonseca Brito L, Stanelle-Bertram S, Krasemann S, Frascaroli G, Thiele K, Wieczorek A, Felber N, Lütgehetmann M, Markert UR, Hecher K, Brune W, Stahl F, Gabriel G, Diemert A, Arck PC.
Front Immunol. 2021 Jun 3;12:698578. doi:10.3389/fimmu.2021.698578. PMID: 34149740; PMCID: PMC8211452.
Vertically Transferred Immunity in Neonates: Mothers,
Mechanisms and Mediators
Albrecht M, Arck PC. 2020 Mar 31;11:555. doi:
10.3389/fimmu.2020.00555. PMID: 32296443; PMCID: PMC7136470
When 3 Rs meet a forth R: Replacement, reduction and refinement of animals in research on reproduction
Arck PC. When 3 Rs meet a forth R: Replacement, reduction and refinement of animals in research on reproduction. J Reprod Immunol. 2019 Apr;132:54-59. doi: 10.1016/j.jri.2019.03.004.
Epub 2019 Mar 25. PMID: 30951977.
Immunological implications of pregnancy-induced microchimerism
Kinder JM, Stelzer IA, Arck PC, Way SS. Nat Rev Immunol. 2017 Aug;17(8):483-494. doi:10.1038/nri.2017.38. Epub 2017 May 8.
PMID: 28480895; PMCID: PMC5532073.
Pregnancy-Related Immune Adaptation Promotes the
Emergence of Highly Virulent H1N1 Influenza Virus Strains in Allogenically Pregnant Mice
Engels G, Hierweger AM, Hoffmann J, Thieme R, Thiele S, Bertram S, Dreier C, Resa-Infante P, Jacobsen H, Thiele K, Alawi M, Indenbirken D, Grundhoff A, Siebels S, Fischer N, Stojanovska V, Muzzio D, Jensen F, Karimi K, Mittrücker HW, Arck PC, Gabriel G.
Cell Host Microbe. 2017 Mar 8;21(3):321-333. doi: 10.1016/j.chom.2017.02.020. PMID: 28279344.