Background: Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by repeated skin exposure to contact allergens. The goal of this pilot study was to identify inflammatory proteins which can serve as biomarkers for ACD. Methods: We measured levels of 102 cytokines, chemokines, and growth factors in the sera of 16 ACD patients during acute and remission phases, and 16 healthy volunteers. Results: Serum levels of adiponectin, chemokine (C-C motif) ligand 5 (CCL5), C-reactive protein (CRP), chitinase 3-like 1 (CHI3L1), complement factor D (CFD), endoglin, lipocalin-2, osteopontin, retinol-binding protein 4 (RBP4), and platelet factor 4 (PF4) were significantly higher, whereas levels of trefoil factor 3 (TFF3) were significantly lower, in ACD patients than in healthy controls. In ACD patients, serum levels of CCL5 were elevated, whereas levels of TFF3, soluble intercellular adhesion molecule-1 (sICAM-1), and platelet-derived growth factor (PDGF)-AB/BB were found to be lower during the remission phase of the disease. Conclusions: Serum levels of adiponectin, CCL5, CRP, CHI3L1, CFD, endoglin, lipocalin-2, osteopontin, RBP4, PF4, and TFF3 might be exploited as biomarkers for ACD, whereas levels of CCL5, TFF3, sICAM-1, and PDGF-AB/BB might be exploited for evaluation of disease progression and efficacy of ACD treatment.

Keywords:
Allergic contact dermatitis, Cytokine, Serum biomarkers
1.
Thyssen JP, Linneberg A, Menne T, Johansen JD: The epidemiology of contact allergy in the general population - prevalence and main findings. Contact Dermatitis 2007;57:287-299.
2.
Simonsen AB, Deleuran M, Johansen JD, Sommerlund M: Contact allergy and allergic contact dermatitis in children - a review of current data. Contact Dermatitis 2011;65:254-265.
3.
Martin SF: Immunological mechanisms in allergic contact dermatitis. Curr Opin Allergy Clin Immunol 2015;15:124-130.
4.
Herbst RA, Lauerma AI, Maibach HI: Intradermal testing in the diagnosis of allergic contact dermatitis. A reappraisal. Contact Dermatitis 1993;29:1-5.
5.
Hansen MB, Skov L, Menne T, Olsen J: Gene transcripts as potential diagnostic markers for allergic contact dermatitis. Contact Dermatitis 2005;53:100-106.
6.
Sakaguchi H, Ashikaga T, Miyazawa M, Yoshida Y, Ito Y, Yoneyama K, Hirota M, Itagaki H, Toyoda H, Suzuki H: Development of an in vitro skin sensitization test using human cell lines; human cell line activation test (h-CLAT). II. An inter-laboratory study of the h-CLAT. Toxicol In Vitro 2006;20:774-784.
7.
Dickel H, Kreft B, Kuss O, Worm M, Soost S, Brasch J, Pfutzner W, Grabbe J, Angelova-Fischer I, Elsner P, Fluhr J, Altmeyer P, Geier J: Increased sensitivity of patch testing by standardized tape stripping beforehand: a multicentre diagnostic accuracy study. Contact Dermatitis 2010;62:294-302.
8.
Stejskal VD, Forsbeck M, Nilsson R: Lymphocyte transformation test for diagnosis of isothiazolinone allergy in man. J Invest Dermatol 1990;94:798-802.
9.
Lisby S, Hansen LH, Skov L, Menne T, Baadsgaard O: Nickel-induced activation of T cells in individuals with negative patch test to nickel sulphate. Arch Dermatol Res 1999;291:247-252.
10.
Jakobson E, Masjedi K, Ahlborg N, Lundeberg L, Karlberg AT, Scheynius A: Cytokine production in nickel-sensitized individuals analysed with enzyme-linked immunospot assay: possible implication for diagnosis. Br J Dermatol 2002;147:442-449.
11.
Rustemeyer T, von Blomberg BM, van Hoogstraten IM, Bruynzeel DP, Scheper RJ: Analysis of effector and regulatory immune reactivity to nickel. Clin Exp Allergy 2004;34:1458-1466.
12.
Bordignon V, Palamara F, Cordiali-Fei P, Vento A, Aiello A, Picardo M, Ensoli F, Cristaudo A: Nickel, palladium and rhodium induced IFN-gamma and IL-10 production as assessed by in vitro ELISpot-analysis in contact dermatitis patients. BMC Immunol 2008;9:19.
13.
Bordignon V, Palamara F, Altomonte G, Sperduti I, Pietravalle M, Cavallotti C, Cordiali-Fei P, Fuggetta MP, Cristaudo A, Ensoli F: A laboratory test based on determination of cytokine profiles: a promising assay to identify exposition to contact allergens and predict the clinical outcome in occupational allergic contact dermatitis. BMC Immunol 2015;16:4.
14.
Cavani A, Nasorri F, Prezzi C, Sebastiani S, Albanesi C, Girolomoni G: Human CD4+ T lymphocytes with remarkable regulatory functions on dendritic cells and nickel-specific Th1 immune responses. J Invest Dermatol 2000;114:295-302.
15.
Cheng X, Folco EJ, Shimizu K, Libby P: Adiponectin induces pro-inflammatory programs in human macrophages and CD4+ T cells. J Biol Chem 2012;287:36896-36904.
16.
Van Vre EA, Bult H, Hoymans VY, Van Tendeloo VF, Vrints CJ, Bosmans JM: Human C-reactive protein activates monocyte-derived dendritic cells and induces dendritic cell-mediated T-cell activation. Arterioscler Thromb Vasc Biol 2008;28:511-518.
17.
Ouwehand K, Scheper RJ, de Gruijl TD, Gibbs S: Epidermis-to-dermis migration of immature Langerhans cells upon topical irritant exposure is dependent on CCL2 and CCL5. Eur J Immunol 2010;40:2026-2034.
18.
Floderer M, Prchal-Murphy M, Vizzardelli C: Dendritic cell-secreted lipocalin2 induces CD8+ T-cell apoptosis, contributes to T-cell priming and leads to a Th1 phenotype. PLoS One 2014;9:e101881.
19.
Weiss JM, Renkl AC, Maier CS, Kimmig M, Liaw L, Ahrens T, Kon S, Maeda M, Hotta H, Uede T, Simon JC: Osteopontin is involved in the initiation of cutaneous contact hypersensitivity by inducing Langerhans and dendritic cell migration to lymph nodes. J Exp Med 2001;194:1219-1229.
20.
Johansen JS: Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer. Dan Med Bull 2006;53:172-209.
21.
Witkowska AM, Borawska MH: Soluble intercellular adhesion molecule-1 (sICAM-1): an overview. Eur Cytokine Netw 2004;15:91-98.
22.
Paulsen FP, Woon CW, Varoga D, Jansen A, Garreis F, Jager K, Amm M, Podolsky DK, Steven P, Barker NP, Sel S: Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds. J Biol Chem 2008;283:13418-13427.
23.
Chen CF, Feng X, Liao HY, Jin WJ, Zhang J, Wang Y, Gong LL, Liu JJ, Yuan XH, Zhao BB, Zhang D, Chen GF, Wan Y, Guo J, Yan HP, He YW: Regulation of T cell proliferation by JMJD6 and PDGF-BB during chronic hepatitis B infection. Sci Rep 2014;4:6359.
© 2016 S. Karger AG, Basel
2016
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.