| Summary: | Despite recent advancements in human immune-genetics, graft-versus-host
disease (GvHD) continues to be the major and potentially fatal complication of
hematopoietic stem cell transplantations affecting up to 80% of transplant patients
[1]. Very little is known regarding the pathophysiologic mechanisms behind the
manifestation of either acute or chronic GvHD. Diagnosis and treatment assessment
are often hindered as they rely primarily on ambiguous clinical symptoms, such as
tissue inflammation. It is likely that the outcome for patients diagnosed with GvHD
could be improved if they were treated in a pre-emptive fashion, before the
development of full-scale clinical symptoms.
Using flow cytometry high content screening [2], 123 subsets of immune cells
were identified from blood samples taken at multiple time points from 31 patients
who underwent allogenic bone marrow transplantations. I assembled a novel
analysis pipeline specifically designed to process this high-throughput clinical flow
cytometry dataset. The pipeline included a novel quality assurance test [3] and
temporal classification via functional linear discriminant analysis [4]. Temporal
patterns of multiple immune cell abundances both after the transplantation and
around the acute GvHD diagnosis were screened for potential discriminative power
for either acute or chronic GvHD.
Among many potential discriminative patterns: higher proportion values in
immune cell with CD3⁺CD4⁺CD8β⁺ phenotype were found in acute GvHD patients
(21), compared to the patients unaffected by GvHD (3), between zero and 120 days
post-transplant. I also generated a list of recommendations for an extended study
designed to validate the current findings. The global approach of the highthroughput
flow cytometry technique and the novel temporal analysis pipeline,
implemented according to the list of recommendations would be beneficial in elucidating pathophysiologic mechanisms of complex immunologically based
diseases including GvHD. === Science, Faculty of === Graduate
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