To understand molecular-immunologic processes in human-environment interactions is our research focus to improve diagnostics and therapy of the individual patient.
In contrast to large epidemiologic studies, we focus on rare monogenic diseases. Monogenic diseases allow a direct connection of gene defect, the consequential immunologic impairment, and clinical presentation. With the gained immunologic insights from our research, we develop novel diagnostic and research approaches.
In the center of our translational research are so-called inborn errors of atopic disease, a group of monogenic diseases presenting with allergy or atopic findings as one of the leading symptoms.
Here, hyper-IgE syndromes (HIES) are of particular interest to us. HIES are a group of rare inborn errors of immunity. In infancy HIES resemble atopic dermatitis. When the disease progresses, patients present with recurrent infections of skin and airways, which potentially lead to irreversible lung disease. Therefore, an early diagnosis is essential to prevent irreversible disease complications.
Since the differential diagnosis of inborn errors of immunity from diseases such as atopic dermatitis, asthma or allergies is challenging, we are developing molecular-genetic diagnostic procedures for many years.
Selection of our milestones on molecular-genetic diagnostics:
- original description of autosomal-recessive HIES (Renner et al. J. Ped. 2004), now called DOCK8-deficiency
- association of gene defects in STAT3 with the autosomal-dominant form of HIES and low TH17-cell blood counts (Renner et al. NEJM 2007, Renner et al. JACI 2008)
- complex molecular-genetic diagnostics of disease (Spielberger et al. JACI 2012 and Hagl&Spielberger et al. SciRep 2018).
To understand the effect of impaired molecular mechanisms on disease development and the environmental impact on the course of disease is another focus of our research. Currently, we are particularly addressing immunity in the context of recurrent infections with Staphyloccocus aureus (Stentzel et al. Clin Infect Dis. 2017, van de Veen&Krätz et al. Allergy 2019).
Based on the two previous subjects, our third research interest is to transfer our knowledge to improve and advance health care (=translational research).
Here, we showed that applying the treatment regimen of cystic fibrosis to STAT3-HIES patients in combination with immunoglobulin substitution therapy is beneficial to improve patients’ quality of life (Kröner et al. Allergy 2020).
In recent years, we had a major breakthrough in the development of an innovative therapeutic option of STAT3-HIES by functional repair of patient fibroblasts and induced pluripotent stem cells (iPSCs) by CRISPR/Cas9-based gene editing technology (Eberherr et al. CRISPR J 2021).
Our vision is to develop a curative treatment approach to repair destructive lung disease in STAT3-HIES e.g. by cell replacement therapy.
We are grateful for the generous financial support by:
German Research Association (DFG)
Helmholtz Future topic "Immunology and Inflammation" (ZT-0027)
Fritz Thyssen Foundation
Job Research Foundation
Christine Kühne – Center for Allergy Research and Education (CK-CARE)
and intramural support by Helmholtz Center Munich, LMU, and TUM.