Background: The pathogenesis of hidradenitis suppurativa (HS), with its complex inflammatory network, is still elusive. Imbalances in DNA methylation can lead to genome destabilization and have been assumed to play a role in inflammatory diseases. Global DNA methylation and hydroxymethylation have not been studied in HS yet. Objective: We conducted this study to investigate the global DNA methylation and hydroxymethylation status in lesional and perilesional HS skin compared to healthy controls. Methods: Immunohistochemical analysis was performed for 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in 30 lesional and 30 corresponding healthy-appearing perilesional HS tissue samples. We included 30 healthy subjects as an interindividual control group. Results: 5-hmC levels were significantly lower in healthy-appearing perilesional (p < 0.0001) and lesional HS skin (p < 0.0001) when compared to healthy controls. There was no significant difference between lesional HS skin and perilesional HS skin regarding 5-hmC levels (p = 0.6654). In contrast to 5-hmC, 5-mC staining showed no significant changes between the 3 groups. Univariate analysis revealed no significant association between patients' characteristics, disease severity, and the levels of 5-mC and 5-hmC. Conclusion: Our findings indicate that imbalances in DNA hydroxymethylation may play a role in the pathogenesis of HS rather than DNA methylation. Further studies are warranted to investigate the significance of DNA hydroxymethylation and the regulating enzymes in HS in order to advance our knowledge of the inflammatory network in this disease.

1.
Hessam S, Sand M, Georgas D, Anders A, Bechara FG: Microbial profile and antimicrobial susceptibility of bacteria found in inflammatory hidradenitis suppurativa lesions. Skin Pharmacol Physiol 2016;29:161-167.
2.
Kirschke J, Hessam S, Bechara FG: Hidradenitis suppurativa/acne inversa: an update (in German). Hautarzt 2015;66:413-422.
3.
Sartorius K, Emtestam L, Jemec GBE, Lapins J: Objective scoring of hidradenitis suppurativa reflecting the role of tobacco smoking and obesity. Br J Dermatol 2009;161:831-839.
4.
Danby FW, Jemec GBE, Marsch WC, von Laffert M: Preliminary findings suggest hidradenitis suppurativa may be due to defective follicular support. Br J Dermatol 2013;168:1034-1039.
5.
von der Werth JM, Williams HC: The natural history of hidradenitis suppurativa. J Eur Acad Dermatol Venereol 2000;14:389-392.
6.
Liu M, Davis JWJ, Idler KB, Mostafa NM, Okun MM, Waring JF: Genetic analysis of the NCSTN gene for potential association to hidradenitis suppurativa in familial and non-familial subjects. Br J Dermatol 2016;175:414-416.
7.
Melnik BC, Plewig G: Impaired Notch signalling: the unifying mechanism explaining the pathogenesis of hidradenitis suppurativa (acne inversa). Br J Dermatol 2013;168:876-878.
8.
Ingram JR, Wood M, John B, Butler R, Anstey AV: Absence of pathogenic γ-secretase mutations in a South Wales cohort of familial and sporadic hidradenitis suppurativa (acne inversa). Br J Dermatol 2013;168:874-876.
9.
Wang B, Yang W, Wen W, Sun J, Su B, Liu B, et al: γ-Secretase gene mutations in familial acne inversa. Science 2010;330:1065.
10.
Pink AE, Simpson M a, Desai N, Trembath RC, Barker JNW: γ-Secretase mutations in hidradenitis suppurativa: new insights into disease pathogenesis. J Invest Dermatol 2013;133:601-607.
11.
Millington GWM: Epigenetics and dermatological disease. Pharmacogenomics 2008;9:1835-1850.
12.
Strickland FM, Richardson BC: Epigenetics in human autoimmunity. Epigenetics in autoimmunity - DNA methylation in systemic lupus erythematosus and beyond. Autoimmunity 2008;41:278-286.
13.
Grolleau-Julius A, Ray D, Yung RL: The role of epigenetics in aging and autoimmunity. Clin Rev Allergy Immunol 2010;39:42-50.
14.
Chen I-P, Henning S, Faust A, Boukamp P, Volkmer B, Greinert R: UVA-induced epigenetic regulation of P16(INK4a) in human epidermal keratinocytes and skin tumor derived cells. Photochem Photobiol Sci 2012;11:180-190.
15.
Tan L, Shi YG: Tet family proteins and 5-hydroxymethylcytosine in development and disease. Development 2012;139:1895-1902.
16.
Saito S, Kato J, Hiraoka S, Horii J, Suzuki H, Higashi R, et al: DNA methylation of colon mucosa in ulcerative colitis patients: correlation with inflammatory status. Inflamm Bowel Dis 2011;17:1955-1965.
17.
Zhang P, Su Y, Lu Q: Epigenetics and psoriasis. J Eur Acad Dermatol Venereol 2012;26:399-403.
18.
Calabrese R, Valentini E, Ciccarone F, Guastafierro T, Bacalini MG, Ricigliano VA, et al: TET2 gene expression and 5-hydroxymethylcytosine level in multiple sclerosis peripheral blood cells. Biochim Biophys Acta 2014;1842:1130-1136.
19.
Hessam S, Sand M, Gambichler T, Bechara FG: Correlation of inflammatory serum markers with disease severity in patients with hidradenitis suppurativa (HS). J Am Acad Dermatol 2015;73:998-1005.
20.
McClelland RA, Finlay P, Walker KJ, Nicholson D, Robertson JF, Blamey RW, et al: Automated quantitation of immunocytochemically localized estrogen receptors in human breast cancer. Cancer Res 1990;50:3545-3550.
21.
Ficz G, Branco MR, Seisenberger S, Santos F, Krueger F, Hore TA, et al: Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 2011;473:398-402.
22.
Lian CG, Xu Y, Ceol C, Wu F, Larson A, Dresser K, et al: Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell 2012;150:1135-1146.
23.
Branco MR, Ficz G, Reik W: Uncovering the role of 5-hydroxymethylcytosine in the epigenome. Nat Rev Genet 2012;13:7-13.
24.
Kroeze LI, van der Reijden BA, Jansen JH: 5-Hydroxymethylcytosine: an epigenetic mark frequently deregulated in cancer. Biochim Biophys Acta 2015;1855:144-154.
25.
Wang J, Tang J, Lai M, Zhang H: 5-Hydroxymethylcytosine and disease. Mutat Res Rev Mutat Res 2014;762:167-175.
26.
Taylor SEB, Smeriglio P, Dhulipala L, Rath M, Bhutani N: A global increase in 5-hydroxymethylcytosine levels marks osteoarthritic chondrocytes. Arthritis Rheumatol 2014;66:90-100.
27.
Haseeb A, Makki MS, Haqqi TM: Modulation of ten-eleven translocation 1 (TET1), isocitrate dehydrogenase (IDH) expression, α- ketoglutarate (α-KG), and DNA hydroxymethylation levels by interleukin-1β in primary human chondrocytes. J Biol Chem 2014;289:6877-6885.
28.
Kelly G, Hughes R, McGarry T, van den Born M, Adamzik K, Fitzgerald R, et al: Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa. Br J Dermatol 2015;173:1431-1439.
29.
van der Zee HH, de Ruiter L, van den Broecke DG, Dik WA, Laman JD, Prens EP: Elevated levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-α and IL-1β. Br J Dermatol 2011;164:1292-1298.
30.
Wolk K, Warszawska K, Hoeflich C, Witte E, Schneider-Burrus S, Witte K, et al: Deficiency of IL-22 contributes to a chronic inflammatory disease: pathogenetic mechanisms in acne inversa. J Immunol 1950 2011;186:1228-1239.
31.
Zhang Q, Zhao K, Shen Q, Han Y, Gu Y, Li X, et al: Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature 2015;525:389-393.
32.
Cheng J, Guo S, Chen S, Mastriano SJ, Liu C, D'Alessio AC, et al: An extensive network of TET2-targeting microRNAs regulates malignant hematopoiesis. Cell Rep 2013;5:471-481.
33.
Jacobsen A, Silber J, Harinath G, Huse JT, Schultz N, Sander C: Analysis of microRNA-target interactions across diverse cancer types. Nat Struct Mol Biol 2013;20:1325-1332.
34.
Hessam S, Sand M, Skrygan M, Gambichler T, Bechara FG: Inflammation induced changes in the expression levels of components of the microRNA maturation machinery Drosha, Dicer, Drosha co-factor DGRC8 and Exportin-5 in inflammatory lesions of hidradenitis suppurativa patients. J Dermatol Sci 2016;82:166-174.
35.
Gao X, Jia M, Zhang Y, Breitling LP, Brenner H: DNA methylation changes of whole blood cells in response to active smoking exposure in adults: a systematic review of DNA methylation studies. Clin Epigenetics 2015;7:113.
36.
Foley DL, Craig JM, Morley R, Olsson CA, Olsson CJ, Dwyer T, et al: Prospects for epigenetic epidemiology. Am J Epidemiol 2009;169:389-400.
37.
Yung RL, Julius A: Epigenetics, aging, and autoimmunity. Autoimmunity 2008;41:329-335.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.