Large‐scale serum analysis identifies unique systemic biomarkers in psoriasis and hidradenitis suppurativa. (21st October 2021)

• Record Type: Journal Article
• Authors: Navrazhina, K.; Renert‐Yuval, Y.; Frew, J.W.; Grand, D.; Gonzalez, J.; Williams, S.C.; Garcet, S.; Krueger, J.G.
• Is Part Of: British journal of dermatology. Volume 186:Number 4(2022)
• Page Start: 684
• Page End: 693
• Publication Date: 2021-10-21
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.20642
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Background: Hidradenitis suppurativa (HS) is now recognized as a systemic inflammatory disease, sharing molecular similarities with psoriasis. Direct comparison of the systemic inflammation in HS with psoriasis is lacking. Objectives: To evaluate the serum proteome of HS and psoriasis, and to identify biomarkers associated with disease severity. Methods: In this cross‐sectional study, 1536 serum proteins were assessed using the Olink Explore (Proximity Extension Assay) high‐throughput panel in patients with moderate‐to‐severe HS ( n = 11), patients with psoriasis ( n = 10) and age‐ and body mass index‐matched healthy controls ( n = 10). Results: HS displayed an overall greater dysregulation of circulating proteins, with 434 differentially expressed proteins (absolute fold change ≥ 1·2; P ≤ 0·05) in patients with HS vs. controls, 138 in patients with psoriasis vs. controls and 503 between patients with HS and patients with psoriasis. Interleukin (IL)‐17A levels and T helper (Th)1/Th17 pathway enrichment were comparable between diseases, while HS presented greater tumour necrosis factor‐ and IL‐1β‐related signalling. The Th17‐associated markers peptidase inhibitor 3 (PI3) and lipocalin 2 (LCN2) were able to differentiate psoriasis from HS accurately. Both diseases presented increases of atherosclerosis‐related proteins. Robust correlations between clinical severity scores and immune and atherosclerosis‐related proteins were observed across both diseases. Conclusions: HS and psoriasis share significant Th1/Th17 enrichment and upregulation of atherosclerosis‐related proteins. Despite the greater body surface area involved in psoriasis, HS presents a greater serum inflammatory burden. Abstract : What is already known about this topic? Psoriasis is an inflammatory skin disease whose molecular profile has been extensively characterized, which has allowed the development of highly efficacious and pathway‐specific treatments. Psoriasis and hidradenitis suppurativa (HS) share overlapping immunological features, enabling the introduction of therapeutics originally developed for psoriasis into the HS therapeutic arena. Understanding of the mechanisms underlying HS is still lacking, potentially hindering the development of HS‐targeted treatments. What does this study add? By utilizing the largest panel of serum biomarkers to date, this study characterizes and compares the systemic dysregulation in serum of patients with psoriasis and HS. Despite a limited area of lesional involvement in HS, patients present with high systemic inflammation and an increase in cardiovascular/atherosclerosis‐related biomarkers. Robust correlations between clinical severity scores and immune and atherosclerosis‐related proteins were found across both diseases. What is the translational message? HS exhibits an overall greater dysregulation of circulating proteins than psoriasis. While T helper (Th)1/Th17 pathway enrichment was comparable between diseases, HS presented greater tumour necrosis factor and interleukin‐1β‐related involvement. A model using peptidase inhibitor 3 (PI3) and lipocalin 2 (LCN2) levels was able to differentiate the diseases accurately. These findings suggest that HS presents a great systemic burden despite limited skin involvement, with disease‐specific biomarkers that may be therapeutically targetable. Plain language summary available online