A preliminary study of soluble CD14 levels in the serum of patients with hidradenitis suppurativa as a marker of “leaky gut”

Daniel G W Johnston; Roisin Hambly; Niamh Kearney; Desmond J Tobin; Brian Kirby

doi:10.12688/hrbopenres.13633.1

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Research Note

A preliminary study of soluble CD14 levels in the serum of patients with hidradenitis suppurativa as a marker of “leaky gut”

[version 1; peer review: 2 not approved]

Daniel G W Johnston^1,2, Roisin Hambly³, Niamh Kearney³, Desmond J Tobin^2,4^*, Brian Kirby^2,3^*

Daniel G W Johnston^1,2, Roisin Hambly³, [...] Niamh Kearney³, Desmond J Tobin^2,4^*, Brian Kirby^2,3^*

^* Equal contributors

PUBLISHED 25 Oct 2022

Author details Author details

¹ Discipline of Anatomy, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, D02 R590, Ireland
² UCD Charles Institute of Dermatology, University College Dublin, Dublin, D04 C7X2, Ireland
³ Charles Centre for Dermatology, Saint Vincent's University Hospital, Dublin, D04 T6F4, Ireland
⁴ Conway Institute for Biomedical and Biomolecular Sciences, University College Dublin, Dublin, D04 C7X2, Ireland

Daniel G W Johnston
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Writing – Original Draft Preparation, Writing – Review & Editing

Roisin Hambly
Roles: Investigation, Resources, Writing – Review & Editing

Niamh Kearney
Roles: Investigation, Resources, Writing – Review & Editing

Desmond J Tobin
Roles: Funding Acquisition, Project Administration, Resources, Supervision, Writing – Review & Editing

Brian Kirby
Roles: Funding Acquisition, Project Administration, Resources, Supervision, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

Abstract

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurring inflammatory lesions resulting from the rupture of occluded hair follicles. The aetiology of this disease is poorly understood, but it is clear that numerous immunological pathways are dysregulated, both locally and systemically. It is also increasingly appreciated that the gut and skin microbiomes of HS patients are deleteriously altered. Several lines of evidence indicate that this may lead to a “leaky gut” in HS patients, including the strong prevalence of Crohn’s disease as a co-morbidity, resulting in excessive bacterial translocation and lipopolysaccharide (LPS) circulation.
Methods: We sought to investigate whether soluble CD14, a proxy for circulating LPS and subsequent excessive monocyte activation, was elevated in the serum of HS patients. sCD14 levels in HS patients from a Dublin hospital were assessed using ELISA.
Results: We found that there was no significant difference in sCD14 levels present in the plasma of 12 healthy controls and 17 HS patients.
Conclusions: Our results indicate that sCD14 is not a useful marker of inflammation in HS patients and does not indicate a grossly compromised gut epithelial barrier.

Keywords

Hidradenitis suppurativa, dermatology, CD14, biomarker, LPS, inflammation

Corresponding author: Daniel G W Johnston

Competing interests: No competing interests were disclosed.

Grant information: Health Research Board Fulbright Health Impact scholarship [Fulbright-2021-2] awarded to Dr Daniel Johnston. This work was also supported by a Newman Fellowship awarded by UCD Foundation.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright: © 2022 Johnston DGW et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Johnston DGW, Hambly R, Kearney N et al. A preliminary study of soluble CD14 levels in the serum of patients with hidradenitis suppurativa as a marker of “leaky gut” [version 1; peer review: 2 not approved]. HRB Open Res 2022, 5:68 (https://doi.org/10.12688/hrbopenres.13633.1) First published: 25 Oct 2022, 5:68 (https://doi.org/10.12688/hrbopenres.13633.1) Latest published: 25 Oct 2022, 5:68 (https://doi.org/10.12688/hrbopenres.13633.1)

Introduction

Hidradenitis suppurativa (HS) is a highly prevalent inflammatory skin disease, affecting 1–4% of the general population¹. It has a significant impact on patient quality of life, worse than other common conditions such as psoriasis and atopic dermatitis, with patients often suffering from multiple psychological co-morbidities such as depression². HS is characterized by recurrent abscesses which derive from the rupture of occluded hair follicles, but the aetiology of the disease is still poorly understood. It is known that the immune system is dysregulated in multiple ways in the skin and blood of HS patients¹. Pro-inflammatory cytokines such as interleukin (IL)-1β and IL-6 are elevated in HS patients and may result from increased infiltration of monocytes and macrophages into the skin^3,4. The causes of this immune dysregulation are unknown, but there is increased recognition that systemic factors may play a role in the disease. Crohn’s disease is a major co-morbidity of HS and is associated with significant impairment of the gut epithelial barrier⁵ termed "leaky gut". The gut and skin microbiomes of HS patients have been shown to be dysregulated, pointing towards a disrupted immunity barrier and a deleterious relationship between host and microbe in these patients^6–9. A leaky gut allows bacterial translocation from the gut lumen into circulation, leading to increased circulation of bacterial lipopolysaccharide (LPS)¹⁰. LPS is an agonist of innate immune receptors such as Toll-like receptor (TLR) 4, activating signalling pathways which result in pro-inflammatory cytokine release. LPS is presented to TLR4 via the adaptor molecules LPS-binding protein (LBP) and CD14¹¹. In response to the presence of excess LPS, monocytes can release CD14 in a soluble form (sCD14) which is a well described biomarker in diseases with barrier impairments¹⁰. Diseases that feature elevated patient sCD14 levels include acute and chronic conditions such as sepsis and HIV respectively, and notably the inflammatory skin condition atopic dermatitis^12–17. CD14 release from cell membranes in sepsis is governed by P2X7 receptor, which is also elevated in HS¹⁸. CD14 is primarily expressed by myeloid cells, such as monocytes and macrophages, which are overrepresented in HS patients³. Given the dysregulation of the microbiome, myeloid cell compartment and cutaneous inflammation associations we hypothesized that patients with HS have a leaky gut barrier. To address this, we sought to determine the levels of sCD14 present in the serum of HS patients as a proxy marker.

Methods

Ethics statements

The study was approved in advance by the Ethics and Medical Research Committee of St Vincent’s University Hospital (approval date 2/10/2019 and 11/02/2020). Written, signed informed consent was obtained via signature from each participant for sample collection, data collection and publication of results. Patient data was processed at sites covered under ethics approval provided by the Ethics and Medical Research Committee of St Vincent’s University Hospital. For this study, the data was de-identified using the Safe Harbour method and is available via Open Science Framework¹⁹.

Sample collection and analysis

Blood was collected from 17 HS patients as part of their routine clinical visits to St Vincent’s University Hospital, and from nine healthy volunteers at the Charles Institute of Dermatology, University College Dublin. Samples were collected during monthly clinics between September 2020 and March 2021 at once off appointments with no follow-up. Healthy controls were deemed eligible if they were healthy and did not suffer from any inflammatory or infectious disease. HS patients were deemed eligible upon attendance of the HS clinic at Charles Centre for Dermatology, St Vincent’s University Hospital to treat their condition. HS patients recruited were not excluded based on current or previous therapeutic regimens. Of the HS patients, 41% were not undergoing treatment for their HS, 24% were being treated with anti-TNF biologics (adalimumab and infliximab), 6% were being treated with anti-IL-17 antibodies (brodalumab), 18% were being treated with Rifampicin and clindamycin and 12% were treated with other antibiotics (lymecyclin and sprinolcatone). 30% of HS patients were smokers, 35% were ex-smokers and 35% were non-smokers. Of the healthy controls, 77% were non-smokers, 11% were current and 11% were ex-smokers. The study size was determined with reference to similar studies in the literature with similar estimated effect sizes^4,20. A total of 5 ml of patient blood was collected using the BD Vacutainer system into BD Serum collection tubes (Becton, Dickinson U.K. Limited). These tubes were allowed to rest for 30 min at room temperature before centrifugation at 10,000 rpm for 10 min at 4°C. The serum was removed from the clot and immediately aliquoted in fresh polypropylene tubes and frozen at -80°C. Immediate freezing and aliquoting was done to remove day-to-day variability between sample collections and to prevent unwanted freeze-thaw artefacts, respectively. Once the sCD14 was measured in healthy control and HS serum by enzyme linked immunosorbent assay (ELISA) using Quantikine sCD14 ELISA kits (RnDSystems, Abingdon, UK). Serum was diluted 1 in 200 in reagent diluent included as part of the kit as per the manufacturer’s instructions. Absorbance at 450 nm was detected using a SpectraMax M3 plate reader with SoftMax Pro Version 6 analysis software (Molecular Devices, San Jose, CA, USA). Statistical analysis of the difference between the mean sCD14 levels of the control group and the HS group was performed using GraphPad Prism Version 9.00 (GraphPad Software, La Jolla, CA, USA.) and an unpaired Student’s t-test with significance of P <0.05 and correlation analysis using data recorded as part of the patient’s routine clinical examination or self-reported by healthy controls was performed using Spearman’s rank correlation co-efficient. Underlying data are available as a .csv file for analysis using SPSS and R can be used as an alternative open-source statistical analysis software¹⁹. Where patient data was incomplete (e.g. some HS BMI measurements) it has been indicated in the figure legends for clarity.

Results

The mean serum level of sCD14 was not significantly different in patients with HS (5.021 ng/ml ± 2.223, n = 17) when compared to healthy controls (3.680 μg/ml ± 1.691, n = 12, P = 0.09). This result is presented in Figure 1, and the accompanying patient demographics are presented in Table 1. In addition, to rule out differences in body mass index and age (BMI) which may impact interpretation of the results, sCD14 levels were correlated against BMI and age where this data was available. No significant correlations were observed, as presented in Figure 2. In addition, no correlation was found between sCD14 levels and C-reactive protein (CRP) levels measured at time of serum sampling as presented in Figure 3.

Figure 1. Soluble CD14 levels in healthy controls (HC) and patients with hidradenitis suppurativa (HS).

Dot plot represents individual samples (HS=square, HC=circles) with mean levels of soluble CD14 levels (red line) in each group. P=0.0902 by unpaired Student’s t-test.

Table 1. Demographics of healthy controls (HC) and hidradenitis suppurativa (HS) patients.

	N	Age [years]		BMI		Female	Male
	N	mean	range	mean	range	Female	Male
HS	17	38	27–54	35 (n=10)	24–54 (n=10)	13	4
HC	12	31	21–55	<25	22–26	7	5

Figure 2.

Correlation analysis of soluble CD14 levels with (a) age and (b) BMI in healthy controls (HC) and patients with hidradenitis suppurativa (HS). For b), n=9 and 10 respectively. Dot plot represents individual samples (HS=red, HC=black). r values derived from Spearman’s rank correlation co-efficient test.

Figure 3. Correlation analysis of soluble CD14 levels with C-reactive protein (CRP) levels in patients with hidradenitis suppurativa (HS).

N=9 and 14 respectively. Dot plot represents individual samples. r values derived from Spearman’s rank correlation co-efficient test.

Discussion and conclusions

Our data demonstrate no statistically significant increase in sCD14 in HS patients, nor any correlation with age, BMI or circulating CRP levels. The clearest conclusion to draw from this study is that elevated sCD14 does not serve as an indicator of leaky gut in HS patients. This may be due to the absence of leaky gut in this condition, the presence of alternative redundant mechanisms, or a lesser degree of “leakiness” relative to other conditions. It is interesting in the context of the reported microbial dysregulation in the gut and skin of HS patients and may be a reflection of a low level of gut barrier disruption over a chronic time period as distinct from a more acute event. Commensal microbial involvement in inflammatory disease is complex and multi-faceted, and these results may point towards altered host:microbe interactions in non-innate immune compartments such as T and B cell responses. Several studies have demonstrated an expansion of plasma and B cell numbers in HS, as well as reports of elevated anti-fungal antibody titres that might point towards one such host:microbe interaction^21–25. Given the p value reported when comparing HS sCD14 levels to that of healthy controls, it could be concluded that this study is not large enough and includes too few patients. However, we believe that the study is sufficiently powered to capture any significant differences according to previously reported effect sizes^16,17. This may not be the case for correlation analysis, which may indeed require a larger study to properly interrogate. One limitation of this study is the fact that most of the patients (15/17) were Hurley Stage 2, which does not allow for analysis by disease stage. It would be interesting to test this hypothesis in a larger cohort of patients of varying disease severity, and with additional co-morbidities such as Crohn’s disease. In summary, these data do not indicate that sCD14 levels are indicative of a leaky gut in HS patients, but do not rule out a link between the disease and gastrointestinal dysfunction.

Consent

Written informed consent for publication of the patients’ details was obtained from the patients.

Data availability

Underlying data

Open Science Framework: Underlying data for ‘A preliminary study of soluble CD14 levels in the serum of patients with hidradenitis suppurativa as a marker of “leaky gut”’. “sCD14 in hidradenitis suppurativa”. https://doi.org/10.17605/OSF.IO/C9Y2W¹⁹.

This project contains the following underlying data:

Data file 1: HRB-OR_sCD14_ELISA.csv - raw data in open-source CSV format
Data file 2: HRB-OR_sCD14_ELISA.xlsx - raw data in Microsoft Excel format
Data file 3: HRB-OR_sCD14.pzf - processed data in GraphPad Prism format

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)

Faculty Opinions recommended

References

1. Johnston DGW, Kirby B, Tobin DJ: Hidradenitis suppurativa: A folliculotropic disease of innate immune barrier dysfunction? Exp Dermatol. 2021; 30(10): 1554–68. PubMed Abstract | Publisher Full Text
2. Nguyen TV, Damiani G, Orenstein LAV, et al.: Hidradenitis suppurativa: an update on epidemiology, phenotypes, diagnosis, pathogenesis, comorbidities and quality of life. J Eur Acad Dermatol Venereol. 2021; 35(1): 50–61. PubMed Abstract | Publisher Full Text
3. van der Zee HH, de Ruiter L, Boer J, et al.: Alterations in leucocyte subsets and histomorphology in normal-appearing perilesional skin and early and chronic hidradenitis suppurativa lesions. Br J Dermatol. 2012; 166(1): 98–106. PubMed Abstract | Publisher Full Text
4. Kelly G, Hughes R, McGarry T, et al.: Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa. Br J Dermatol. 2015; 173(6): 1431–9. PubMed Abstract | Publisher Full Text
5. Zhang M, Chen QD, Xu HX, et al.: Association of hidradenitis suppurativa with Crohn's disease. World J Clin Cases. 2021; 9(15): 3506–16. PubMed Abstract | Publisher Full Text | Free Full Text
6. Naik HB, Jo JH, Paul M, et al.: Skin Microbiota Perturbations Are Distinct and Disease Severity-Dependent in Hidradenitis Suppurativa. J Invest Dermatol. 2020; 140(4): 922–5.e3. PubMed Abstract | Publisher Full Text | Free Full Text
7. McCarthy S, Barrett M, Kirthi S, et al.: Altered Skin and Gut Microbiome in Hidradenitis Suppurativa. J Invest Dermatol. 2022; 142(2): 459–68.e15. PubMed Abstract | Publisher Full Text
8. Ring HC, Bay L, Nilsson M, et al.: Bacterial biofilm in chronic lesions of hidradenitis suppurativa. Br J Dermatol. 2017; 176(4): 993–1000. PubMed Abstract | Publisher Full Text
9. Ring HC, Thorsen J, Saunte DM, et al.: The Follicular Skin Microbiome in Patients With Hidradenitis Suppurativa and Healthy Controls. JAMA Dermatol. 2017; 153(9): 897–905. PubMed Abstract | Publisher Full Text | Free Full Text
10. Hoshiko H, Feskens EJM, Oosterink E, et al.: Identification of leaky gut-related markers as indicators of metabolic health in Dutch adults: The Nutrition Questionnaires plus (NQplus) study. PLoS One. 2021; 16(6): e0252936. PubMed Abstract | Publisher Full Text | Free Full Text
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12. Thijs JL, Strickland I, Bruijnzeel-Koomen C, et al.: Moving toward endotypes in atopic dermatitis: Identification of patient clusters based on serum biomarker analysis. J Allergy Clin Immunol. 2017; 140(3): 730–7. PubMed Abstract | Publisher Full Text
13. Yaegashi Y, Shirakawa K, Sato N, et al.: Evaluation of a newly identified soluble CD14 subtype as a marker for sepsis. J Infect Chemother. 2005; 11(5): 234–8. PubMed Abstract | Publisher Full Text
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16. Lien E, Aukrust P, Sundan A, et al.: Elevated levels of serum-soluble CD14 in human immunodeficiency virus type 1 (HIV-1) infection: correlation to disease progression and clinical events. Blood. 1998; 92(6): 2084–92. PubMed Abstract | Publisher Full Text
17. Wüthrich B, Kägi MK, Joller-Jemelka H: Soluble CD14 but not interleukin-6 is a new marker for clinical activity in atopic dermatitis. Arch Dermatol Res. 1992; 284(6): 339–42. PubMed Abstract | Publisher Full Text
18. Alarcón-Vila C, Baroja-Mazo A, de Torre-Minguela C, et al.: CD14 release induced by P2X7 receptor restricts inflammation and increases survival during sepsis. eLife. 2020; 9: e60849. PubMed Abstract | Publisher Full Text | Free Full Text
19. Johnston DGW: sCD14 in hidradenitis suppurativa. OSF. [Dataset], 2022. http://www.doi.org/10.5923/27518
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21. Gudjonsson JE, Tsoi LC, Ma F, et al.: Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis. JCI Insight. 2020; 5(19): e139930. PubMed Abstract | Publisher Full Text | Free Full Text
22. Lowe MM, Naik HB, Clancy S, et al.: Immunopathogenesis of hidradenitis suppurativa and response to anti-TNF-α therapy. JCI Insight. 2020; 5(19): e139932. PubMed Abstract | Publisher Full Text | Free Full Text
23. Moran B, Sweeney CM, Hughes R, et al.: Hidradenitis Suppurativa Is Characterized by Dysregulation of the Th17:Treg Cell Axis, Which Is Corrected by Anti-TNF Therapy. J Invest Dermatol. 2017; 137(11): 2389–95. PubMed Abstract | Publisher Full Text
24. Musilova J, Moran B, Sweeney CM, et al.: Enrichment of Plasma Cells in the Peripheral Blood and Skin of Patients with Hidradenitis Suppurativa. J Invest Dermatol. 2020; 140(5): 1091–1094.e2. PubMed Abstract | Publisher Full Text
25. Assan F, Gottlieb J, Tubach F, et al.: Anti-Saccharomyces cerevisiae IgG and IgA antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa. J Allergy Clin Immunol. 2020; 146(2): 452–455.e5. PubMed Abstract | Publisher Full Text

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Version 1

VERSION 1 PUBLISHED 25 Oct 2022

Author details Author details

¹ Discipline of Anatomy, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, D02 R590, Ireland
² UCD Charles Institute of Dermatology, University College Dublin, Dublin, D04 C7X2, Ireland
³ Charles Centre for Dermatology, Saint Vincent's University Hospital, Dublin, D04 T6F4, Ireland
⁴ Conway Institute for Biomedical and Biomolecular Sciences, University College Dublin, Dublin, D04 C7X2, Ireland

Daniel G W Johnston
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Writing – Original Draft Preparation, Writing – Review & Editing

Roisin Hambly
Roles: Investigation, Resources, Writing – Review & Editing

Niamh Kearney
Roles: Investigation, Resources, Writing – Review & Editing

Desmond J Tobin
Roles: Funding Acquisition, Project Administration, Resources, Supervision, Writing – Review & Editing

Brian Kirby
Roles: Funding Acquisition, Project Administration, Resources, Supervision, Writing – Review & Editing

Competing interests

No competing interests were disclosed.

Grant information

Health Research Board Fulbright Health Impact scholarship [Fulbright-2021-2] awarded to Dr Daniel Johnston. This work was also supported by a Newman Fellowship awarded by UCD Foundation.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Published: 25 Oct 2022, 5:68

https://doi.org/10.12688/hrbopenres.13633.1

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© 2022 Johnston DGW et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Johnston DGW, Hambly R, Kearney N et al. A preliminary study of soluble CD14 levels in the serum of patients with hidradenitis suppurativa as a marker of “leaky gut” [version 1; peer review: 2 not approved]. HRB Open Res 2022, 5:68 (https://doi.org/10.12688/hrbopenres.13633.1)

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Reviewer Report 05 Jul 2023

Rafael Luís Luporini, Department of Medicine, Federal University of São Carlos (UFSCar), São Carlos, Brazil

Not Approved

https://doi.org/10.21956/hrbopenres.14905.r34605

The considerations presented above as inadequate refer to the lack of a sample calculation that justifies the small number of patients studied in both the HS group and the control group. It is possible that the lack of statistical significance ... Continue reading

The considerations presented above as inadequate refer to the lack of a sample calculation that justifies the small number of patients studied in both the HS group and the control group. It is possible that the lack of statistical significance is due to the apparent small number of participants in the study. The authors' reasoning that they believe the size is appropriate based on previous publications is not appropriate because the populations involved are very different (HIV and dermatitis).

Is the work clearly and accurately presented and does it cite the current literature?

Partly
Is the study design appropriate and is the work technically sound?

Partly
Are sufficient details of methods and analysis provided to allow replication by others?

Partly
If applicable, is the statistical analysis and its interpretation appropriate?

No
Are all the source data underlying the results available to ensure full reproducibility?

Yes
Are the conclusions drawn adequately supported by the results?

No

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Inflammatory cytokines, Crohn's disease, Ulcerative colitis, Hidradenitis suppurativa

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

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Reviewer Report 28 Jun 2023

Chiara Moltrasio, Dermatology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

Not Approved

https://doi.org/10.21956/hrbopenres.14905.r34599

The rationale of this study would be sound. Based on literature, the authors determine the levels of sCD14 present in the serum of HS patients as a proxy marker. The idea is good but I think that the experimental design ... Continue reading

The rationale of this study would be sound. Based on literature, the authors determine the levels of sCD14 present in the serum of HS patients as a proxy marker. The idea is good but I think that the experimental design is not appropriate. The authors should have selected a "homogeneous" patient's cohort. For example, the authors should have selected patients with moderate-to severe degree of disease, non-smokers, in the absence of comorbidities, and after pharmacological wash-out.
It cannot be ruled out, because the full pathogenetic mechanisms underlying HS are not yet known, whether or not treatment with other biologics may affect sCD14 levels.

Is the work clearly and accurately presented and does it cite the current literature?

Yes
Is the study design appropriate and is the work technically sound?

No
Are sufficient details of methods and analysis provided to allow replication by others?

Yes
If applicable, is the statistical analysis and its interpretation appropriate?

Partly
Are all the source data underlying the results available to ensure full reproducibility?

Yes
Are the conclusions drawn adequately supported by the results?

No

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Autoinflammatory skin diseases; genodermatoses; genetics.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

CITE

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Chiara Moltrasio, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Rafael Luís Luporini, Federal University of São Carlos (UFSCar), São Carlos, Brazil

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05 Jul 2023 | for Version 1

Rafael Luís Luporini, Department of Medicine, Federal University of São Carlos (UFSCar), São Carlos, Brazil

25 Views Cite this report Responses(0)

Not Approved

The considerations presented above as inadequate refer to the lack of a sample calculation that justifies the small number of patients studied in both the HS group and the control group. It is possible that the lack of statistical significance is due to the apparent small number of participants in the study. The authors' reasoning that they believe the size is appropriate based on previous publications is not appropriate because the populations involved are very different (HIV and dermatitis).

Is the work clearly and accurately presented and does it cite the current literature?

Partly
Is the study design appropriate and is the work technically sound?

Partly
Are sufficient details of methods and analysis provided to allow replication by others?

Partly
If applicable, is the statistical analysis and its interpretation appropriate?

No
Are all the source data underlying the results available to ensure full reproducibility?

Yes
Are the conclusions drawn adequately supported by the results?

No

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Inflammatory cytokines, Crohn's disease, Ulcerative colitis, Hidradenitis suppurativa

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

Respond to this report

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Reviewer Report

25 Views

28 Jun 2023 | for Version 1

Chiara Moltrasio, Dermatology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

25 Views Cite this report Responses(0)

Not Approved

The rationale of this study would be sound. Based on literature, the authors determine the levels of sCD14 present in the serum of HS patients as a proxy marker. The idea is good but I think that the experimental design is not appropriate. The authors should have selected a "homogeneous" patient's cohort. For example, the authors should have selected patients with moderate-to severe degree of disease, non-smokers, in the absence of comorbidities, and after pharmacological wash-out.
It cannot be ruled out, because the full pathogenetic mechanisms underlying HS are not yet known, whether or not treatment with other biologics may affect sCD14 levels.

Is the work clearly and accurately presented and does it cite the current literature?

Yes
Is the study design appropriate and is the work technically sound?

No
Are sufficient details of methods and analysis provided to allow replication by others?

Yes
If applicable, is the statistical analysis and its interpretation appropriate?

Partly
Are all the source data underlying the results available to ensure full reproducibility?

Yes
Are the conclusions drawn adequately supported by the results?

No

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Autoinflammatory skin diseases; genodermatoses; genetics.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

Respond to this report

Responses (0)

[1] 1. Johnston DGW, Kirby B, Tobin DJ: Hidradenitis suppurativa: A folliculotropic disease of innate immune barrier dysfunction? Exp Dermatol. 2021; 30(10): 1554–68. PubMed Abstract | Publisher Full Text

[2] 2. Nguyen TV, Damiani G, Orenstein LAV, et al.: Hidradenitis suppurativa: an update on epidemiology, phenotypes, diagnosis, pathogenesis, comorbidities and quality of life. J Eur Acad Dermatol Venereol. 2021; 35(1): 50–61. PubMed Abstract | Publisher Full Text

[3] 3. van der Zee HH, de Ruiter L, Boer J, et al.: Alterations in leucocyte subsets and histomorphology in normal-appearing perilesional skin and early and chronic hidradenitis suppurativa lesions. Br J Dermatol. 2012; 166(1): 98–106. PubMed Abstract | Publisher Full Text

[4] 4. Kelly G, Hughes R, McGarry T, et al.: Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa. Br J Dermatol. 2015; 173(6): 1431–9. PubMed Abstract | Publisher Full Text

[5] 5. Zhang M, Chen QD, Xu HX, et al.: Association of hidradenitis suppurativa with Crohn's disease. World J Clin Cases. 2021; 9(15): 3506–16. PubMed Abstract | Publisher Full Text | Free Full Text

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A preliminary study of soluble CD14 levels in the serum of patients with hidradenitis suppurativa as a marker of “leaky gut”

Abstract

Keywords

Introduction