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In-Depth Analysis of the Hidradenitis Suppurativa Serum Proteome Identifies Distinct Inflammatory Subtypes.

ABSTRACT: Hidradenitis suppurativa is a chronic inflammatory dermatosis with presentations ranging from painful nodules and abscesses to draining tunnels. Using an unbiased proteomics approach, we assessed cardiovascular-, cardiometabolic-, and inflammation-related biomarkers in the serum of patients with moderate-to-severe hidradenitis suppurativa. The serum of patients with hidradenitis suppurativa clustered separately from that of healthy controls and had an upregulation of neutrophil-related markers (Cathepsin D, IL-17A, CXCL1). Patients with histologically diagnosed dermal tunnels had higher serum lipocalin-2 levels compared with those without tunnels. Consistent with this, patients with tunnels had a more neutrophilic-rich serum signature, marked by Cathepsin D, IL-17A, and IL-17D alterations. There was a significant serum‒skin correlation between proteins in the serum and the corresponding mRNA expression in skin biopsies, with healthy-appearing perilesional skin demonstrating a significant correlation with neutrophil-related proteins in the serum. CSF3 mRNA levels in lesional skin significantly correlated with neutrophil-related proteins in the serum, suggesting that CFS3 in the skin may be a driver of neutrophilic inflammation. Clinical significantly correlated with the levels of lipocalin-2 and IL-17A in the serum. Using an unbiased, large-scale proteomic approach, we demonstrate that hidradenitis suppurativa is a systemic neutrophilic dermatosis, with a specific molecular signature associated with the presence of dermal tunnels.

SUBMITTER: Navrazhina K

PROVIDER: S-EPMC8384651 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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In-Depth Analysis of the Hidradenitis Suppurativa Serum Proteome Identifies Distinct Inflammatory Subtypes.

Navrazhina Kristina K Garcet Sandra S Gonzalez Juana J Grand David D Frew John W JW Krueger James G JG

The Journal of investigative dermatology 20210322 9

Hidradenitis suppurativa is a chronic inflammatory dermatosis with presentations ranging from painful nodules and abscesses to draining tunnels. Using an unbiased proteomics approach, we assessed cardiovascular-, cardiometabolic-, and inflammation-related biomarkers in the serum of patients with moderate-to-severe hidradenitis suppurativa. The serum of patients with hidradenitis suppurativa clustered separately from that of healthy controls and had an upregulation of neutrophil-related markers ( ...[more]

PMID: 33766512

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Project description:ImportanceHidradenitis suppurativa (HS) and inflammatory bowel disease (IBD) are inflammatory diseases that share common genetic susceptibility and immunologic features. However, the link between HS and IBD has been largely unclear.ObjectiveTo conduct a meta-analysis to investigate the association between HS and IBD.Data sourcesA search of the MEDLINE, Cochrane Central Register of Controlled Trials, and Embase databases yielded 397 relevant studies from inception to June 10, 2018. Two additional studies were supplied by one of the investigators.Study selectionCase-control, cross-sectional, or cohort studies that examined the odds or risk of IBD in patients with HS were included. No geographic or language limitations were imposed.Data extraction and synthesisThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The Newcastle-Ottawa Scale was used to assess the risk of bias of included studies. Crohn disease and ulcerative colitis were analyzed separately, and a random-effects model meta-analysis was conducted.Main outcomes and measuresThe odds ratios (ORs) and hazard ratios (HRs) of IBD, Crohn disease, and ulcerative colitis in association with HS.ResultsFive case-control studies, 2 cross-sectional studies, and 1 cohort study with a total of 93 601 unique participants were included. The meta-analysis of case-control and cross-sectional studies showed significant associations of HS with Crohn disease (pooled OR, 2.12; 95% CI, 1.46-3.08) and ulcerative colitis (pooled OR, 1.51; 95% CI, 1.25-1.82). Two case-control studies found significant association of HS with IBD (ORs, 2.16 [95% CI, 1.40-3.34] and 10.00 [95% CI, 1.94-51.50]). One cohort study found an increased risk of IBD in patients with HS (HR, 5.6; 95% CI not reported; P < .002).Conclusions and relevanceThe evidence to date supports an association of HS with IBD. These results suggest that consultation with gastroenterologists should be sought when patients with HS present with recurrent abdominal pain, chronic diarrhea, bloody stool, and body weight loss.

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In-Depth Analysis of the Hidradenitis Suppurativa Serum Proteome Identifies Distinct Inflammatory Subtypes.

Publications

In-Depth Analysis of the Hidradenitis Suppurativa Serum Proteome Identifies Distinct Inflammatory Subtypes.

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