Abstract
BackgroundPodoconiosis 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.MethodsNanoString 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.ResultsForty-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.ConclusionsThis 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.
Highlights
Podoconiosis, known as endemic non-filarial elephantiasis, is a progressive lymphoedema of the lower limb observed in people living and working barefoot on red clay soils of volcanic origin.[1]
Purified RNA samples were successfully obtained from femoral lymph node blocks of podoconiosis patients and controls
Low RNA integrity number (RIN) scores are considered typical for archival formalin-fixed and paraffin-embedded (FFPE) extractions.[20]
Summary
Podoconiosis, known as endemic non-filarial elephantiasis, is a progressive lymphoedema of the lower limb observed in people living and working barefoot on red clay soils of volcanic origin.[1] Recent evaluation of the worldwide distribution and burden of podoconiosis identified its presence in 32 countries, with tropical African regions being the worst affected.[2,3] Globally, approximately 4 million people have podoconiosis. The resulting fibrogenic inflammatory response causes obstruction of lymphatic drainage This in turn leads to swelling of the feet and legs, which progresses. 4 million people are affected, mainly in African highland regions. The pathogenesis of this neglected tropical disease is still largely unknown, HLA class II (HLAII) polymorphisms are associated with the disease
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