Integrating the skin and blood transcriptomes and serum proteome in hidradenitis suppurativa reveals complement dysregulation and a plasma cell signature.

Hidradenitis suppurativa (HS) is a chronic skin disease of the pilo-sebaceous apocrine unit characterized by significant inflammation and an impaired quality of life. The pathogenesis of HS remains unclear. To determine the HS skin and blood transcriptomes and HS blood proteome, patient data from pr...

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Main Authors: Lauren K Hoffman, Lewis E Tomalin, Gregory Schultz, Michael D Howell, Niroshana Anandasabapathy, Afsaneh Alavi, Mayte Suárez-Fariñas, Michelle A Lowes
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC6162087?pdf=render
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author Lauren K Hoffman
Lewis E Tomalin
Gregory Schultz
Michael D Howell
Niroshana Anandasabapathy
Afsaneh Alavi
Mayte Suárez-Fariñas
Michelle A Lowes
author_facet Lauren K Hoffman
Lewis E Tomalin
Gregory Schultz
Michael D Howell
Niroshana Anandasabapathy
Afsaneh Alavi
Mayte Suárez-Fariñas
Michelle A Lowes
author_sort Lauren K Hoffman
collection DOAJ
description Hidradenitis suppurativa (HS) is a chronic skin disease of the pilo-sebaceous apocrine unit characterized by significant inflammation and an impaired quality of life. The pathogenesis of HS remains unclear. To determine the HS skin and blood transcriptomes and HS blood proteome, patient data from previously published studies were analysed and integrated from a cohort of patients with moderate to severe HS (n = 17) compared to healthy volunteers (n = 10). The analysis utilized empirical Bayes methods to determine differentially expressed genes (DEGs) (fold change (FCH) >2.0 and false discovery rate (FDR) <0.05), and differentially expressed proteins (DEPs) (FCH>1.5, FDR<0.05). In the HS skin transcriptome (lesional skin compared to non-lesional skin), there was an abundance of immunoglobulins, antimicrobial peptides, and an interferon signature. Gene-sets related to Notch signalling and Interferon pathways were differentially activated in lesional compared to non-lesional skin. CIBERSORT analysis of the HS skin transcriptome revealed a significantly increased proportion of plasma cells in lesional skin. In the HS skin and blood transcriptomes and HS blood proteome, gene-sets related to the complement system changed significantly (FDR<0.05), with dysregulation of complement-specific DEGs and DEPs. These data point towards an exaggerated immune response in lesional skin that may be responding to commensal cutaneous bacterial presence and raise the possibility that this may be an important driver of HS disease progression.
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spelling doaj.art-f8fdfa2a137140a9887ee403d2476ff22022-12-22T02:01:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01139e020367210.1371/journal.pone.0203672Integrating the skin and blood transcriptomes and serum proteome in hidradenitis suppurativa reveals complement dysregulation and a plasma cell signature.Lauren K HoffmanLewis E TomalinGregory SchultzMichael D HowellNiroshana AnandasabapathyAfsaneh AlaviMayte Suárez-FariñasMichelle A LowesHidradenitis suppurativa (HS) is a chronic skin disease of the pilo-sebaceous apocrine unit characterized by significant inflammation and an impaired quality of life. The pathogenesis of HS remains unclear. To determine the HS skin and blood transcriptomes and HS blood proteome, patient data from previously published studies were analysed and integrated from a cohort of patients with moderate to severe HS (n = 17) compared to healthy volunteers (n = 10). The analysis utilized empirical Bayes methods to determine differentially expressed genes (DEGs) (fold change (FCH) >2.0 and false discovery rate (FDR) <0.05), and differentially expressed proteins (DEPs) (FCH>1.5, FDR<0.05). In the HS skin transcriptome (lesional skin compared to non-lesional skin), there was an abundance of immunoglobulins, antimicrobial peptides, and an interferon signature. Gene-sets related to Notch signalling and Interferon pathways were differentially activated in lesional compared to non-lesional skin. CIBERSORT analysis of the HS skin transcriptome revealed a significantly increased proportion of plasma cells in lesional skin. In the HS skin and blood transcriptomes and HS blood proteome, gene-sets related to the complement system changed significantly (FDR<0.05), with dysregulation of complement-specific DEGs and DEPs. These data point towards an exaggerated immune response in lesional skin that may be responding to commensal cutaneous bacterial presence and raise the possibility that this may be an important driver of HS disease progression.http://europepmc.org/articles/PMC6162087?pdf=render
spellingShingle Lauren K Hoffman
Lewis E Tomalin
Gregory Schultz
Michael D Howell
Niroshana Anandasabapathy
Afsaneh Alavi
Mayte Suárez-Fariñas
Michelle A Lowes
Integrating the skin and blood transcriptomes and serum proteome in hidradenitis suppurativa reveals complement dysregulation and a plasma cell signature.
PLoS ONE
title Integrating the skin and blood transcriptomes and serum proteome in hidradenitis suppurativa reveals complement dysregulation and a plasma cell signature.
title_full Integrating the skin and blood transcriptomes and serum proteome in hidradenitis suppurativa reveals complement dysregulation and a plasma cell signature.
title_fullStr Integrating the skin and blood transcriptomes and serum proteome in hidradenitis suppurativa reveals complement dysregulation and a plasma cell signature.
title_full_unstemmed Integrating the skin and blood transcriptomes and serum proteome in hidradenitis suppurativa reveals complement dysregulation and a plasma cell signature.
title_short Integrating the skin and blood transcriptomes and serum proteome in hidradenitis suppurativa reveals complement dysregulation and a plasma cell signature.
title_sort integrating the skin and blood transcriptomes and serum proteome in hidradenitis suppurativa reveals complement dysregulation and a plasma cell signature
url http://europepmc.org/articles/PMC6162087?pdf=render
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