University of Sussex
Browse
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

Download (2.15 MB)
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 Newport
Background 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 Hygiene

ISSN

0035-9203

Publisher

Oxford University Press

Issue

12

Volume

114

Page range

926-936

Event location

England

Department affiliated with

  • Global Health and Infection Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2021-11-17

First Open Access (FOA) Date

2021-11-17

First Compliant Deposit (FCD) Date

2021-11-16

Usage metrics

    University of Sussex (Publications)

    Categories

    No categories selected

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC