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

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...

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Autores principales: Alcantara, Diana R, Jones, Christopher I, Altmann, Daniel M, Boyton, Rosemary J, Haniffa, Muzlifah, Newport, Melanie J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738654/
https://www.ncbi.nlm.nih.gov/pubmed/33099652
http://dx.doi.org/10.1093/trstmh/traa107
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author Alcantara, Diana R
Jones, Christopher I
Altmann, Daniel M
Boyton, Rosemary J
Haniffa, Muzlifah
Newport, Melanie J
author_facet Alcantara, Diana R
Jones, Christopher I
Altmann, Daniel M
Boyton, Rosemary J
Haniffa, Muzlifah
Newport, Melanie J
author_sort Alcantara, Diana R
collection PubMed
description 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.
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spelling pubmed-77386542020-12-21 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 Newport, Melanie J Trans R Soc Trop Med Hyg Special Issue 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. Oxford University Press 2020-10-24 /pmc/articles/PMC7738654/ /pubmed/33099652 http://dx.doi.org/10.1093/trstmh/traa107 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Special Issue
Alcantara, Diana R
Jones, Christopher I
Altmann, Daniel M
Boyton, Rosemary J
Haniffa, Muzlifah
Newport, Melanie J
Multiplexed gene expression analysis of HLA class II-associated podoconiosis implicates chronic immune activation in its pathogenesis
title Multiplexed gene expression analysis of HLA class II-associated podoconiosis implicates chronic immune activation in its pathogenesis
title_full Multiplexed gene expression analysis of HLA class II-associated podoconiosis implicates chronic immune activation in its pathogenesis
title_fullStr Multiplexed gene expression analysis of HLA class II-associated podoconiosis implicates chronic immune activation in its pathogenesis
title_full_unstemmed Multiplexed gene expression analysis of HLA class II-associated podoconiosis implicates chronic immune activation in its pathogenesis
title_short Multiplexed gene expression analysis of HLA class II-associated podoconiosis implicates chronic immune activation in its pathogenesis
title_sort multiplexed gene expression analysis of hla class ii-associated podoconiosis implicates chronic immune activation in its pathogenesis
topic Special Issue
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738654/
https://www.ncbi.nlm.nih.gov/pubmed/33099652
http://dx.doi.org/10.1093/trstmh/traa107
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