Multiplexed gene expression analysis of HLA class II-associated podoconiosis implicates chronic immune activation in its pathogenesis

Alcantara, Diana R, Jones, Christopher I, Altmann, Daniel M, Boyton, Rosemary J, Haniffa, Muzlifah and Newport, Melanie J (2020) Multiplexed gene expression analysis of HLA class II-associated podoconiosis implicates chronic immune activation in its pathogenesis. Transactions of the Royal Society of Tropical Medicine and Hygiene, 114 (12). pp. 926-936. ISSN 0035-9203

[img] PDF - Published Version
Available under License Creative Commons Attribution.

Download (2MB)

Abstract

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.

Item Type: Article
Keywords: NanoString, archive, gene expression, immunology, lymph nodes, podoconiosis, Elephantiasis, Ethiopia, Gene Expression, Humans, Lymphedema, Neglected Diseases, Soil
Schools and Departments: Brighton and Sussex Medical School > Global Health and Infection
Brighton and Sussex Medical School > Primary Care and Public Health
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 17 Nov 2021 09:26
Last Modified: 17 Nov 2021 09:30
URI: http://sro.sussex.ac.uk/id/eprint/102951

View download statistics for this item

📧 Request an update