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

• Published in: PloS one Vol. 13; no. 9; p. e0203672
• Main Authors: Hoffman, Lauren K, Tomalin, Lewis E, Schultz, Gregory, Howell, Michael D, Anandasabapathy, Niroshana, Alavi, Afsaneh, Suárez-Fariñas, Mayte, Lowes, Michelle A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.09.2018; Public Library of Science (PLoS)
• Subjects: Antimicrobial peptides; Autoimmune diseases; Bayes Theorem; Bayesian analysis; Biology and Life Sciences; Blood; Blood - metabolism; Blood proteins; Cellular signal transduction; Complement; Complement activation; Cytokines; Data points; Dermatitis; Dermatology; Disease; Empirical analysis; Gangrene; Gene expression; Gene Expression Regulation; Genetic aspects; Genomics; Hidradenitis Suppurativa - genetics; Hidradenitis Suppurativa - metabolism; Humans; Hypotheses; Immune response; Immune system; Immunoglobulins; Interferon; Medicine; Medicine and Health Sciences; Metabolism; Pathogenesis; Patients; Peptides; Plasma cells; Protein expression; Proteins; Proteome; Proteomes; Quality of life; Risk factors; Signal transduction; Signal Transduction - genetics; Skin - metabolism; Skin diseases; Statistical analysis; Transcriptome; Tumor necrosis factor-TNF; New York; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0203672

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.