Programme(s) to which this project applies:
|☑ MPhil/PhD||☒ MRes[Med]||☒ URIS|
Autoimmune and autoinflammatory diseases cause considerable long-term morbidity and mortality, especially in children. There is a need for patient stratification and outcome prediction to tailor immunosuppressive therapy according to deep knowledge of the pathomechanisms underlying immune dysregulation.
To identify immune cell phenotype and transcriptomic signatures that characterise childhood-onset autoimmune and immunodysregulatory disorders, using deep phenotyping methods such as flow cytometry and transcriptomic analysis
Hypothesis to be tested
We hypothesise that paediatric autoimmune and autoinflammatory diseases have distinct immune cell phenotype and gene expression pattern that can predict disease severity and response to specific disease-modifying treatment.
Standardised disease activity measurement, immunophenotyping by flow cytometry, transcriptome profiling by RNA-sequencing
Patients will be evaluated at diagnosis / disease relapse and after drug treatment for detailed phenotyping of clinical manifestations, immune cells and transcriptome
Main outcome measures
Cellular subsets and transcriptome signatures that are predictive of disease remission or persistence
Proportion of immune cell subpopulations in each disease entity will be compared in patients before and after treatment at specified time-points, using age-matched healthy controls as reference. Differentially expressed genes identified from transcriptome profiling of T-cells, B-cells and neutrophils will be analysed for pathway enrichment and mapping through bioinformatics pipeline. Genes and pathways that characterise each disease, and those modulated by treatment, will be identified.
Distinct cellular subpopulations and corresponding gene expression can identify pathways that can be targeted by biologic response modifiers, enabling treatment of autoimmune and autoinflammatory disease using a personalised medicine approach.
Dr PPW Lee, Department of Paediatrics and Adolescent Medicine
Field of Research
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