Tailored Immunotherapy for Paediatric SIRS (TIPS)

TIPS is a project on personalised medicine for improved understanding and management of paediatric severe inflammatory response syndrome (SIRS). SIRS, which can affect children without predisposing factors is a life-threatening event due to an uncontrolled activation of the immune system as a results of, often, unknown triggers. For the majority of patients, acute management of SIRS is based on clinical features and routine laboratory parameters without distinct stratification, demonstrating the need for better and precise diagnostics. 

We aim to generate personalised immune profiling and to identify diagnostic patterns in order to develop individualized therapies to improve patient outcome. In this transnational endeavour, we will integrate consideration of ethico-legal aspects of patient safety and data protection.

TIPS is designed as a multicenter study linking five institutions from four European countries. Clinicians and scientists work closely together in this interdisciplinary project, covering all disciplines relevant to children's health and development from the fields of medicine, life sciences, ethics and computer science.

Dresden (Germany)

The University Hospital Carl Gustav Carus Dresden is one of the leading healthcare institutions in Germany with a large catchment area beyond Eastern Saxony.As part of the Technische Universität Dresden (TUD) -“University of Excellence” since 2012 -it is committed to highest standards in applied medicine, medical research and teaching. 

At the Children’s Hospitalwe offer state-of-the-art diagnostics and therapeutics, providing care for infants, children, and adolescents with congenital and acquired diseases.In addition, the close connection between patient care and research enables a wide range of clinical and basic research. 

The Dresden team is the coordinator of the European multicentric TIPS study and responsible for organizing and coaching all partners. Additionally, we provide samples and clinical data of SIRS patients beyond the project period. In conjunction with Helsinki, Dresden will lead the immune phenotyping (ImmunOMICs) and lipid profiling (LipidOMICs) of the acquired samples. 

Contact:

Prof. Dr. med. Catharina Schütz

Department of Pediatrics

Pediatric Immunology

University Hospital Carl Gustav Carus

Technische Universität Dresden (TUD)

Fetscherstraße 74

01307 Dresden

Germany


Members:

Prof. Dr. med. Sebastian Brenner

Dr. rer. nat. Sebastian Thieme

Dr. rer. nat. Ralf Wiedemuth

Sissi Lina Fritsch (project coordination)


Link to institution

Helsinki (Finland)

HiLIFE Helsinki Institute of Life Science is one of the leading life science research institutes in the Nordics. It fosters outstanding research and generation of innovations across the University of Helsinki campuses to create an attractive international environment where today’s grand challenges in health are solved.

The Pediatric Research Center is the Finland’s largest research community for pediatric diseases, located in Helsinki. Our research groups are affiliated in the largest Faculty of Medicine in Finland, the largest children’s hospital in the Nordic countries and several other research institutes located in the area. Our research comprises of basic, clinical and translational research. The research data we generate can be refined to be used when treating patients. On the other hand, we use patient samples in the investigation of disease mechanisms and diagnoses.

As a part of this multicentric, international study, the Helsinki team will provide clinical data and collect up samples from pediatric SIRS patients, particularly from those with an underlying autoinflammatory disease. Helsinki team also leads two work packages; the proteome analysis (ProteOMICs); and gene expression profiling (TranscriptOMICs); as well as is the other partner in immunoprofiling (ImmunOMICs).

Contact:

Res. Dir. Dr. Markku Varjosalo

University of Helsinki, HiLIFE – Helsinki Institute of Life Science

Institute of Biotechnology

Biocenter 3

Viikinkaari 1, P.O.Box 65

FI-00014 University of Helsinki

Finland


Members:

Docent Kristiina Aalto (MD, PhD)

Heli Salmi (MD, PhD)

Docent Mikko Seppänen (MD, PhD)



Link to institution

Istanbul (Turkey)

The Istanbul University-Cerrahpasa Medical School, Department for Paediatric Rheumatology is one of the main referral centres for paediatric rheumatology in Turkey. A significant number of patients with autoinflammatory conditions, including Familial Mediterranean fever (FMF) as the most common autoinflammatory entity, places this centre in leading position in the field of autoinflammation. As a part of this multicentric, international study, Istanbul team will provide clinical data and collect up samples from paediatric SIRS patients, particularly from those with an underlying autoinflammatory disease. Consequently, project partners from Istanbul will have the lead for the clinical assessment and translation of study results. Additionally, Istanbul will be responsible for organising the genome sequencing (GenOMICs), to be undertaken by a subcontractor.

Contact:

Prof. Dr. Ozgur Kasapcopur

Istanbul University-Cerrahpasa, Cerrahpasa Medical School

Department of Pediatric Rheumatology

Kocamustafapaşa Cd. No: 53 Cerrahpaş

34098 Fatih/İstanbul

Turkey


Members:

Assoc. Prof. Sezgin Sahin

Assoc. Prof. Fatih Aygun 

Assoc. Prof. Amra Adrovic


Link to institution

Luxembourg (Luxembourg)

The Luxembourgish party is inovolved in the bioinformatics analysis of the generated multiomics data. A novel multiomics-based computational pipeline for patient classification will be developed based on the data generated. First, we aim to identify novel diagnostic patterns/biomarkers that match clinical findings. Then, we will identify accurate predictors for the three major patient groups (groups 1, 2 & 3). Next, a computational algorithm for predicting the clinical outcome of patients will be developed. We also aim to refine this model by including interaction terms for the three groups, 1-like, 2-like, and 3-like. Finally, the model will be validated in a follow-up cohort. Overall, the proposed computational pipeline will enable us to design a composite scoring system to be used by treating physicians, which will aid in future clinical trials of new treatment regimen, such as patient group-adapted treatment intensity versus historical treatment options.

Contact:

Prof. Dr. Antonio del Sol

Biotech II (BT2)

University of Luxembourg

Campus Belval

6, avenue du Swing

L-4367 Belvaux

Luxembourg


Member:

Dr. Satoshi Okawa


Link to institution

Ulm (Germany)

Generating multiOMICs data in paediatric patients raises ethical and legal concerns. Therefore, the aim of the ethical part of the project is to thoroughly study children as vulnerable subjects of research in general, appraise risk-benefit for study participants, debate the responsible use of personal information and data, patient information and informed consent, and deal with challenges posed by different national and regional regulatory frameworks.


The research on ethico-legal aspects will be conducted at Ulm University during the whole duration of the project, parallel to the steps implemented at other research institutes participating in the consortium.

Contact:

Prof. Dr. Florian Steger

Institute of the History, Philosophy and Ethics of Medicine

Ulm University

Parkstraße 11

89073 Ulm

Germany


Members:

Dr. Marcin Orzechowski

Dr. Elisa Groff



Link to institution

Partner

Heinrich-Heine-University Hospital

Department of Pediatrics

Moorenstr. 5 

40225 Düsseldorf

University Hospital Hamburg-Eppendorf 

Department of Pediatrics

Martinistr. 52

20246 Hamburg

Essen University Hospital

Department of pediatics

Infectious Diseases

Hufelandstr. 55

45122 Essen

Jena University Hospital

Department of Pediatrics

Bachstrasse 18 

D-07743 Jena

Department of Pediatrics

Tübingen University Hospital

Hoppe-Seyler-Str. 1

72076 Tübingen

Funding

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