Quantifying lymphocyte vacuolization serves as a measure of CLN3 disease severity

JIMD Reports
Willemijn F E KuperPeter M van Hasselt

Abstract

The CLN3 disease spectrum ranges from a childhood-onset neurodegenerative disorder to a retina-only disease. Given the lack of metabolic disease severity markers, it may be difficult to provide adequate counseling, particularly when novel genetic variants are identified. In this study, we assessed whether lymphocyte vacuolization, a well-known yet poorly explored characteristic of CLN3 disease, could serve as a measure of disease severity. Peripheral blood obtained from healthy controls and CLN3 disease patients was used to assess lymphocyte vacuolization by (a) calculating the degree of vacuolization using light microscopy and (b) quantifying expression of lysosomal-associated membrane protein 1 (LAMP-1), using flow cytometry in lymphocyte subsets as well as a qualitative analysis using electron microscopy and ImageStream analysis. Quantifying lymphocyte vacuolization allowed to differentiate between CLN3 disease phenotypes (P = .0001). On immunofluorescence, classical CLN3 disease lymphocytes exhibited abundant vacuole-shaped LAMP-1 expression, suggesting the use of LAMP-1 as a proxy for lymphocyte vacuolization. Using flow cytometry in lymphocyte subsets, quantifying intracellular LAMP-1 expression additionally allowed to di...Continue Reading

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Mar 11, 2020·JIMD Reports·Willemijn F E KuperPeter M van Hasselt

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Citations

Oct 20, 2020·Acta Ophthalmologica·Willemijn F E KuperMaria M van Genderen
Nov 27, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·An N Dang DoForbes D Porter

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Methods Mentioned

BETA
flow
light microscopy
flow cytometry
FACS

Software Mentioned

FlowJo
ggplot2
nlme
ImageStream
FACS Diva
IDEAS
R project for statistical computing

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