Functional Analysis of Immunocompromised Patients’ Leucocytes by Single-cell Mass Cytometry

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Ressource 1Download: Mémoire no 6879 M. Porret.pdf (530.62 [Ko])
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Download: Mémoire no 6879 Annexes M. Porret.pdf (22758.50 [Ko])
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Serval ID
serval:BIB_E0D00485046A
Type
A Master's thesis.
Publication sub-type
Master (thesis) (master)
Collection
Publications
Institution
Title
Functional Analysis of Immunocompromised Patients’ Leucocytes by Single-cell Mass Cytometry
Author(s)
PORRET R.
Director(s)
PANTALEO G.
Codirector(s)
FENWICK C.
Institution details
Université de Lausanne, Faculté de biologie et médecine
Publication state
Accepted
Issued date
2019
Language
english
Number of pages
40
Abstract
Immunodeficiencies make up a large group of diseases characterized by heterogeneous clinical
manifestations, including life-threatening infections, autoimmunity, chronic inflammation, allergy
and malignant diseases. They are classically divided in primary (PID) and secondary (SID)
immunodeficiencies and they can be caused by monogenic defects or be secondary to exogenous
factors, malignant or non-malignant diseases. In the last 20 years, accelerating progress has been
made in identifying new forms of PIDs thanks to the advances of molecular and genetic
characterizations. These disorders are either diagnosed early in life or even later, in adults. It is
estimated that 1-2% of the population might be affected with any type of the whole PID
spectrum.
Immune cell characterization, particularly by flow cytometry techniques, has extensively showed
its importance in the clinical management of patients presenting immune deficiencies with
quantitative cell defects, as well as in the understanding of the immune system. It has already
improved the classification of immunological diseases, as well as contributed to improve
treatment efficacy and follow-up. Recently, mass cytometry techniques have been used for
diagnostic purposes, significantly increasing the breadth and depth of the functional and
phenotypic characterization of a patient’s immune cells, in comparison to traditional flow
cytometry techniques. These advancements are driven by the great increase in measurable
parameters provided by mass cytometry, which allows for all major known immune cell
populations and subpopulations to be characterized with a single analysis.
The major contribution of this research resides in directly testing the functional activity and
response of a patient's immune cells to different stimuli. The highly multiparametric nature of
mass cytometry allows for both a broad and in depth characterization of the functional immune
response using only a minimal volume of a patient's blood (1 mL) with results available within
one day, thus drastically improving time to diagnosis. In addition to having a proportional and
phenotypic characterization of a patient's immune cells, identifying the functionally abnormal
cell population(s) will provide the clinicians with an even better understanding of their patient's
immunological defect. Interpretation of the mass cytometry results along with the patient's
clinical data will allow for the identification of signatures associated with specific immunological
defects, new classes of immunodeficiencies and therapies that are best adapted to a specific class
of an immunological disorder, hence improving the diagnosis and the benefits for
immunocompromised patients.
Keywords
immunology, immunodeficiency, cytometry, bioinformatics, molecular signatures
Create date
03/09/2020 15:05
Last modification date
05/02/2021 7:11
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