Medizinische Universität Graz - Research portal
Selected Publication:
Koeppen, J.
The Diagnostic, Prognostic, and Predictive Potential of Immune Exhaustion and Senescence Biomarkers in Children and Adolescents with Severe Immune Cytopenias
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2021. pp. 108
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- Authors Med Uni Graz:
- Advisor:
- Karastaneva Anna
- Seidel Markus
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- Abstract:
- Introduction: Severe immune cytopenias (SIC), such as autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP) and Evans syndrome (ES) are syndromes with a remarkable association to immune dysregulation. Immune dysregulation with consequential occurrence of autoimmunity and immune-mediated cytopenia stands in close relationship to premature immunosenescence and a lymphocyte exhaustion phenotype in many inborn errors of immunity (IEI). The patterns of immune phenotypes might be associated with underlying disease mechanisms, and consequently, with treatment responses of SIC in patients with or without a known IEI. Methods: This longitudinal, prospective, multicentric study represents an early interim analysis, based on the Sic-reg.org registry including pediatric and adolescent SIC patients. We included 12 study patients (mean age: 10 years, range: 4-16 years; male, n=5) diagnosed with either AIHA, ITP or ES, of which 3 patients were included as retrospective patients after relapse of their cytopenia. In addition, 19 observational patients with known IEI were analysed. Measurement time points were initially, after 6 and after 12 months. At every time point quantitative FACS analyses of naïve and memory T and B cell subsets and age-associated / senescent lymphocyte subsets were performed. Results: The first observation is that 10 of 12 SIC patients demonstrated a clearly pathological longitudinal pattern of at least one of the naïve or memory or senescent T- or B-lymphocyte subset panels over the first three time points. 8 of 19 observational patients showed at least one pathological longitudinal pattern in a lymphocyte subset. Additionally, certain lymphocyte subsets changed strikingly over time in some patients, allowing a correlation evaluation of these parameters with the clinical courses of the patients. Discussion: Based on these preliminary results the systematic analysis of lymphocytic differentiation patterns should be further elaborated to serve as prognostic and diagnostic biomarker signatures. First, by analysing our follow up measurements, potential adjustments of the applied lymphocyte marker profile could be adapted to a more specific one. Secondly, by expanding the immune phenotypic characterization into broader differentiation of lymphocyte subsets, and thirdly, by combining this data with single-cell transcriptome profiling could yield further insights identifying disease-associated and potentially targetable cell types.