Understanding chronic inflammation in the developing children
Chronic inflammation in childhood
Juvenile idiopathic arthritis (JIA) is the most frequent chronic inflammatory disease in childhood with a prevalence of approximately 1 : 1000. Since the clinical presentation, the prevalence of co-morbidities, and the prognosis of children with JIA differ significantly from adults with different rheumatic diseases, knowledge about the pathogenesis obtained in adults cannot simply be transferred to children. JIA-specific markers for classifying disease subtypes, defining endotypes and predicting therapeutic response are missing.
In cooperation with the research group of Mir-Farzin Mashreghi, we aim to define molecular immune cell signatures in the inflamed synovia and in the peripheral blood of children suffering from different forms of JIA. With these results we will define markers specific for the different forms of JIA which can be traced in peripheral blood. Using data from newly established cohorts, we aim to analyze the suitability of these tools to classify the disease, monitor the disease activity and finally to predict the response to different therapeutic regimens. This translational approach will help to establish JIA-specific endotypes, which are fundamental for the development of personalised treatment strategies.
Monogenic alterations causing systemic inflammatory diseases usually manifest in early childhood. They are characterized by excessive production of pro-inflammatory cytokines and are referred to as autoinflammatory diseases (AID). In the last decade, analysis of these underlying molecular genetic alterations has uncovered new immunological pathomechanisms, e.g. the dysregulation of the inflammasome reaction. Analyzing our cohort of patients with defined, (e.g. interferonopathies, inflammasomopathies) as well as unassigned AID, we aim to comprehensively immunophenotype different immune cell populations in order to develop diagnostic markers and unravel the pathological processes leading to excessive cytokine production.
Juvenile idiopathic arthritis
PD Dr. Tilmann Kallinich
Dr. Carl Christoph Goetzke
Dr. Sae-Lim von Stuckrad
Dr. Banu Orak
- Dr. Dirk Föll, Universität Münster, Klinik für Pädiatrische Rheumatologie und Immunologie, Münster, Germany
- Dr. Raphaela Goldbach-Mansky, National Institut of Health, Translational Autoinflammatory Disease Studies Section, Bethesda, USA
- Dr. Elke Krüger, Universitätsmedizin Greifswald, Institut für Medizinische Biochemie und Molekularbiologie, Greifswald, Germany
- Dr. Klaus Tenbrock, Klinik für Kinder- und Jugendmedizin, Aachen, Germany
1. Patrick Maschmeyer, Gitta Anne Heinz, Christopher Mark Skopnik, Lisanne Lutter, Alessio Mazzoni, Frederik Heinrich, Sae Lim von Stuckrad, Lorenz Elias Wirth, Cam Loan Tran, René Riedel, Katrin Lehmann, Imme Sakwa, Rolando Cimaz, Francesco Giudici, Marcus Alexander Mall, Philipp Enghard, Bas Vastert, Hyun-Dong Chang, Pawel Durek, Francesco Annunziato, Femke van Wijk, Andreas Radbruch*, Tilmann Kallinich*, Mir-Farzin Mashreghi*
Antigen-driven PD-1+TOX+BHLHE40+ and PD-1+TOX+EOMES+ T lymphocytes regulate juvenile idiopathic arthritis in situ
Eur J Immunol. 2020 Dec 9. Epub ahead of print.
2. Orak B, Ngoumou G, Ebstein F, Zieba B, Goetzke CC, Knierim E, Kaindl AM, Panzer A, Theophil M, Berns M, Krüger E, Meisel C, Unterwalder N, Kallinich T.
SIGLEC1 (CD169) as a potential diagnostical screening marker for monogenic interferonopathies
Pediatr Allergy Immunol. 2020 Oct 25. doi: 10.1111/pai.13400
3. Stoler I, Freytag J, Orak B, Unterwalder N, Henning S, Heim K, von Bernuth H, Krüger R, Winkler S, Eschenhagen P, Seipelt E, Mall MA, Foell D, Kessel C, Wittkowski H, Kallinich T.
Gene-Dose Effect of MEFV Gain-of-Function Mutations Determines ex vivo Neutrophil Activation in Familial Mediterranean Fever
Front Immunol. 2020 Jun 11;11:716
4. Outcome of children with oligoarticular juvenile idiopathic arthritis compared to polyarthritis on methotrexate – data of the German BIKER registry
Raab A, Kallinich T, Huscher D, Foeldvari I, Weller-Heinemann F, Dressler F, Kuemmerle-Deschner JB, Klein A, Horneff G. Pediatr Rheumatol Online J. 2021 Mar 22;19(1):41
5. Omarjee S., Quiniou G., Moreews M, Ainouze M., Frachette C., Melki I., Dumaine C., Gerfaud-Valentin M., Duquesne A., Kallinich T., Turanli E., Malcus C., Viel S., Pescarmona R., Georgin-Lavialle S., Jamilloux Y., Larbre J.-P., Sarrabay G, Magnotti F., Rice G., Bleicher F., Reboulet J., Merabet S., Henry T., Crow Y., Faure M., Walzer T., Belot A.
LACC1 deficiency defines a novel form of juvenile arthritis associated with reduced autophagy and metabolism in macrophages.
Journal of Experimental Medicine, 2021 Mar 1;218
6. [Evidence-based treatment recommendations for familial Mediterranean fever : A joint statement by the Society for Pediatric and Adolescent Rheumatology and the German Society for Rheumatology].
Kallinich T, Blank N, Braun T, Feist E, Kiltz U, Neudorf U, Oommen PT, Weseloh C, Wittkowski H, Braun J.
Z Rheumatol. 2019 Feb;78(1):91-101