Multiplexed gene expression analysis of HLA class II-associated podoconiosis implicates chronic immune activation in its pat.pdf (2.15 MB)
Multiplexed gene expression analysis of HLA class II-associated podoconiosis implicates chronic immune activation in its pathogenesis
journal contribution
posted on 2023-06-10, 01:49 authored by Diana AlcantaraDiana Alcantara, Chris JonesChris Jones, Daniel M Altmann, Rosemary J Boyton, Muzlifah Haniffa, Melanie NewportMelanie NewportBackground Podoconiosis is a tropical lymphoedema of the leg resulting from barefoot exposure to irritant volcanic soils. Approximately 4 million people are affected, mainly in African highland regions. The pathogenesis of this neglected tropical disease is still largely unknown, although HLA class II (HLAII) polymorphisms are associated with the disease. Methods NanoString technology was used to assess expression of 579 immune-related genes in formalin-fixed and paraffin-embedded lymph node archival samples from podoconiosis patients and unaffected controls. Results Forty-eight genes were upregulated and 21 downregulated in podoconiosis samples compared with controls. Gene ontology analysis showed differentially expressed genes to be closely related to major histocompatibility complex protein, cytokine and TNF receptor binding genes. Pathway enrichment analysis revealed involvement of lymphocyte activation, adaptive immunity, cytokine signalling, antigen processing and the IL-12 pathways. Conclusions This exploratory study reports a multiplex gene expression analysis in podoconiosis and shows upregulation of pro-inflammatory transcripts compatible with the notion of local, chronic immune activation in this HLAII-associated disease. Implicated pathways will inform future research into podoconiosis immunopathogenesis.
History
Publication status
- Published
File Version
- Published version
Journal
Transactions of the Royal Society of Tropical Medicine and HygieneISSN
0035-9203Publisher
Oxford University PressExternal DOI
Issue
12Volume
114Page range
926-936Event location
EnglandDepartment affiliated with
- Global Health and Infection Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-11-17First Open Access (FOA) Date
2021-11-17First Compliant Deposit (FCD) Date
2021-11-16Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC