Table 2.
Diagnostic Biomarkers (GRADE Moderate/High)
| Biomarker | Statistical association |
Study type | Interpretation | Critical evaluation of biomarkers |
GRADE evidence profile |
References | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Population of comparison |
Significancea | External validation |
Analytical validation | Clinical validation |
Clinical utility |
|||||
| Serum IL-2R | HC | PPV, 0.68; P < .001 | Observational case-control | Elevation associated with HS | Yes | Yes (age, race, and sex matched in Matusiak et al,182015) | No | No | High | Wieland et al,19 2013 |
| HC | P < .001 | Matusiak et al,20 2009 | ||||||||
| HC | PPV, 0.8; P = .001 | Matusiak et al,182015 | ||||||||
| Serum hepcidin | HC | P < .01 | Observational case-control | Decreased levels associated with HS | Yes | No, insufficient info on controls in Ponikowska et al,21 2020 | No | No | Moderate | Ponikowska et al,21 2020 |
| HC | P = .03 | Ghias et al,22 2019 | ||||||||
| Combination of serum markers (E-selectin + VEGF + hBD2) | HC/IBD/staph infection | PPV, 85.3% | Multivariate analysis | Combination of markers identifies individuals with HS | Yes | Yes | No | No | Moderateb | Argyropoulou et al,23 2019b |
| Serum YLK-40/chitinase 3 | HC | PPV, 0.8; P < .001 | Observational case-control | Elevation associated with HS | No | Yes, matched for age, race, and sex | No | No | Moderate | Matusiak et al,18 2015 |
| Serum amyloid A | HC | P < .001 | Observational case-control | Elevation associated with HS | Yes | No, no matching for age or sex in Witte-Handel et al,24 2019 Matched for age and sex in Akdogan et al,25 2020 | No | No | Moderate | Witte-Händel et al,24 2019 |
| P = .008 | Akdogan et al,25 2020 | |||||||||
| Serum CRP | HC | P < .001 | Observational case-control | Elevation associated with HS | Yes | No, matched for age but not sex or BMI in Jiménez-Gallo et al,26 2017 No matching for age, sex or BMI in Jiménez-Gallo et al,27 2018 Matched for age and sex in Akdogan et al,25 2020 | No | No | Moderate | Jiménez-Gallo et al,26 2017 |
| P < .05 | Jiménez-Gallo et al,27 2018 | |||||||||
| P = .01 | Akdogan et al,25 2020 | |||||||||
| Serum IL-8 | HC | P < .01 | Observational case-control | Elevation associated with HS | Yes | No | No | No | Moderate | Jiménez-Gallo et al,27 2018 |
| Upregulated | Witte-Händel et al,24 2019 | |||||||||
| Serum IL-6 | HC | P < .01 | Observational case-control | Elevation associated with HS | Yes | No | No | No | Moderate | Witte-Händel et al,24 2019 |
| P < .001 | Jiménez-Gallo et al,27 2018 | |||||||||
| Serum adiponectin | HC | P < .001 | Observational case-control | Decreased levels associated with HS | Yes | No | No | No | Moderate | González-López et al,28 2020; Özkur et al,29 2020 |
| Serum resistin | HC | OR, 1.02; P = .02 | Elevation associated with HS | Yes | No | No | No | Moderate | ||
| Serum visfatin | HC | OR, 2.21; P < .001 | Elevation associated with HS | Yes | No | No | No | Moderate | ||
| Serum IL-17 | HC | P < .001 | Observational case-control | Elevation associated with HS | Yes | No | No | No | Moderate | Reviewed in Frew et al,4 2021 |
| P < .001 | Matusiak et al,30 2017 | |||||||||
| Serum S100A8/A9 | HC | PPV, 0.81; P < .001 | Observational case-control | Elevation associated with HS | No | Yes | No | No | Moderate | Wieland et al,19 2013 |
| Tissue and serum miRNAs | HC | miRNA-155-5p (P = .005); miRNA-223-p (P < .001); miRNA-31-5p (P = .04); miRNA-21–5p(P < .001); miRNA-146a-5p (P = .01) |
Observational case-control | Elevation associated with HS | Yes | No | No | No | Moderate | Radhakrishna et al,312019; Hessam et al,32 2017 |
| Nonlesional | miRNA-155-5p (P = .01); miRNA-223-5p (P = .01); miRNA-31-5p (P = .048); miRNA-21-5p (P = .01); miRNA-146a-5p (P = .04); miRNA-125b-5p (P = .04) |
Decrease associated with HS | ||||||||
| miRNA 155, 223, and 31 | miRNA-155-5p | P = .01 (L vs NL) | Observational case-control | Elevation associated with HS | Yes | No | No | No | Moderate | Radhakrishna et al,31 2019; Hessam et al,32 2017 |
| miRNA-223-5p | P = .01 | |||||||||
| miRNA-31-5p | P = .048 | |||||||||
| miRNA-21-5p | P = .01 | |||||||||
| miRNA-146a-5p | P = .04 | |||||||||
| miRNA-125b-5p | P = .04 | Decrease associated with HS | ||||||||
| Bacterial species | Corynebacterium (HC) | P < .001 | Observational case-control | Elevation associated with HS | Yes | No | No | No | Moderate | Ring et al,33 2017; Guet-Revillet et al,34 2017; Naik et al,35 2019; Ring et al,36 2019; Schneider et al,37 2020 |
| Acinetobacter/Moraxella (HC) | P = .10 | Yes | No | No | No | Moderate | ||||
| Staphylococcus epidermidis | Not given | Yes | No | No | No | Moderate | ||||
| Porphyromonas/Peptoniphilus (HC) | P = .02 | Yes | No | No | No | Moderate | ||||
| Propionibacterium acnes (NLT) | P < .001 | Yes | No | No | No | Moderate | ||||
| Tissue IL-17 | HC | P < .01 | Observational case-control | Elevation associated with HS | Yes | No, no matching for Witte-Händel et al,24 2019 | No | No | Moderate | Kelly et al,38 2015 |
| P < .001 | Wolk et al,39 2011 | |||||||||
| P < .01 | Hessam et al,40 2018 | |||||||||
| P < .001 | Witte-Händel et al,24 2019 | |||||||||
| Tissue IL-17A | NLT | P = .004 | Observational case-control | Elevation associated with HS | Yes | No | No | No | Moderate | Wolk et al,39 2011 |
| P = .05 | Kelly et al,38 2015 | |||||||||
| P < .001 | Witte-Händel et al,24 2019 | |||||||||
| P < .01 | Hotz et al,41 2016 | |||||||||
| P < .01 | Navrazhina et al,42 2020 | |||||||||
| Tissue IL-17F | NLT | P < .01 | Observational case-control | Elevation associated with HS | Yes | No | No | No | Moderate | Witte-Händel et al,24 2019; Navrazhina et al,42 2020 |
| Tissue IL-1B | HC | P < .01 | Observational case-control | Elevation associated with HS | Yes | No, no matching for age or sex in Witte-Händel et al,24 2019 | No | No | Moderate | Kelly et al,38 2015 |
| HC | P < .001 | Witte-Händel et al,24 2019 | ||||||||
| HC | P < .001 | Wolk et al,39 2011 | ||||||||
| Tissue IL-1B | NLT | 31-Fold increase, P = .003 | Observational case-control | Elevation associated with HS | Yes | No | No | No | Moderate | Wolk et al,39 2011 |
| P < .001 | Kelly et al,38 2015 | |||||||||
| P < .001 | van der Zee et al,43 2011 | |||||||||
| Tissue S100A7 | HC | P < .001 | Observational case-control | Elevation associated with HS | Yes | No | No | No | Moderate | Wolk et al,39 2011 |
| P = .002 | Batycka-Baran et al,44 2021 | |||||||||
| Tissue HBD3 | NLT | P < .05 | Observational case-control | Elevation associated with HS | Yes | No | No | No | Moderate | Wolk et al,39 2011 |
| P < .05 | Emelianov et al,45 2012 | |||||||||
| P < .01 | Multivariate logistic regression | Akdogan et al,25 2020 | ||||||||
| Tissue IFN-γ | NLT | P < .001 | Observational case-control | Elevation associated with HS | Yes | No | No | No | Moderate | Wolk et al,39 2011 |
| P < .01 | Hotz et al,412016 | |||||||||
| Tissue citrullinated H3 protein | HC | P = .03 | Observational case-control | Correlation with disease severity | Yes | No | No | No | Moderate | Byrd et al,46 2019 |
| P < .01 | Lowe et al,47 2020 | |||||||||
| Fecal calprotectin | Inactive disease | P < .001 | Observational case-control | Elevation associated with HS | Yes | No | No | No | Moderate | Eşer et al,48 2020 |
| Descriptive data only | Lloyd-McLennan et al,49 2021 | |||||||||
Abbreviations: BMI, body mass index; CRP, C-reactive protein; GRADE, Grading of Recommendations. Assessment, Development, and Evaluations; HC, healthy controls; HS, hidradenitis suppurativa; IBD, inflammatory bowel disease; L, lesional; miRNA, microRNA; NL, nonlesional; NLT, nonlesional tissue; OR, odds ratio; PPV, positive predictive value; staph, staphylococcus.
a
P values are reported as they were in the original sources.
b
Abstract only.