Digital spatial profiling of collapsing glomerulopathy.
COVID-19–associated nephropathy
HIV-associated nephropathy
collapsing glomerulopathy
digital spatial profiling
kidney biopsy
kidney pathology
Journal
Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
05
08
2021
revised:
08
12
2021
accepted:
13
01
2022
pubmed:
2
3
2022
medline:
27
4
2022
entrez:
1
3
2022
Statut:
ppublish
Résumé
Collapsing glomerulopathy is a histologically distinct variant of focal and segmental glomerulosclerosis that presents with heavy proteinuria and portends a poor prognosis. Collapsing glomerulopathy can be triggered by viral infections such as HIV or SARS-CoV-2. Transcriptional profiling of collapsing glomerulopathy lesions is difficult since only a few glomeruli may exhibit this histology within a kidney biopsy and the mechanisms driving this heterogeneity are unknown. Therefore, we used recently developed digital spatial profiling (DSP) technology which permits quantification of mRNA at the level of individual glomeruli. Using DSP, we profiled 1,852 transcripts in glomeruli isolated from formalin fixed paraffin embedded sections from HIV or SARS-CoV-2-infected patients with biopsy-confirmed collapsing glomerulopathy and used normal biopsy sections as controls. Even though glomeruli with collapsing features appeared histologically similar across both groups of patients by light microscopy, the increased resolution of DSP uncovered intra- and inter-patient heterogeneity in glomerular transcriptional profiles that were missed in early laser capture microdissection studies of pooled glomeruli. Focused validation using immunohistochemistry and RNA in situ hybridization showed good concordance with DSP results. Thus, DSP represents a powerful method to dissect transcriptional programs of pathologically discernible kidney lesions.
Identifiants
pubmed: 35227689
pii: S0085-2538(22)00163-6
doi: 10.1016/j.kint.2022.01.033
pmc: PMC9038707
mid: NIHMS1784261
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1017-1026Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK130386
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
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