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Published in: Clinical and Translational Allergy 1/2018

Open Access 01-12-2018 | Research

Diverse expression of TNF-α and CCL27 in serum and blister of Stevens–Johnson syndrome/toxic epidermal necrolysis

Authors: Fang Wang, Yanting Ye, Ze-Yu Luo, Qian Gao, Di-Qing Luo, Xingqi Zhang

Published in: Clinical and Translational Allergy | Issue 1/2018

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Abstract

Background

The pathogenesis of Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is not fully understood. Our previous study reported that chemokine CCL27 was overexpressed in serum of SJS/TEN patients. The objective of this study was to investigate the levels of CCL27 and TNF-α in serum and blister fluid from patients with SJS/TEN during the acute stage or resolution phase.

Methods

A total of 27 patients with SJS/TEN and 39 healthy donors were recruited to the study. Serum and vesicular levels of CCL27 and TNF-α were determined by enzyme-linked immunosorbent assays.

Results

Serum levels of CCL27 and TNF-α were significantly elevated in patients with SJS/TEN during the acute stage as compared to the resolution phase and also compared with levels observed in normal controls (P = 0.001/< 0.001; P = 0.012/< 0.001). Serum TNF-α levels were significantly higher in patients with SJS/TEN during the resolution phase compared with normal controls (P < 0.001). Serum CCL27 levels were positively correlated with TNF-α levels during the acute stage (r s  = 0.660; P < 0.001). Blister fluid exhibited much lower CCL27 levels than serum did during the acute stage (P = 0.008). TNF-α levels were much higher in vesicles in contrast to serum from acute stage (P = 0.040) as well as serum from resolution phase (P = 0.029).

Conclusions

Our study demonstrated roles of CCL27 and TNF-α in promoting the course of SJS/TEN. CCL27 may act early in the course of disease, via the circulation, whereas TNF-α acts throughout the course of disease, in skin lesions.
Literature
1.
go back to reference Mockenhaupt M. Epidemiology of cutaneous adverse drug reactions. Chem Immunol Allergy. 2012;97:1–17.CrossRefPubMed Mockenhaupt M. Epidemiology of cutaneous adverse drug reactions. Chem Immunol Allergy. 2012;97:1–17.CrossRefPubMed
2.
go back to reference Letko E, Papaliodis DN, Papaliodis GN, Daoud YJ, Ahmed AR, Foster CS. Stevens–Johnson syndrome and toxic epidermal necrolysis: a review of the literature. Ann Allergy Asthma Immunol. 2005;94:419–36.CrossRefPubMed Letko E, Papaliodis DN, Papaliodis GN, Daoud YJ, Ahmed AR, Foster CS. Stevens–Johnson syndrome and toxic epidermal necrolysis: a review of the literature. Ann Allergy Asthma Immunol. 2005;94:419–36.CrossRefPubMed
3.
go back to reference Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med. 1994;331:1272–85.CrossRefPubMed Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med. 1994;331:1272–85.CrossRefPubMed
4.
go back to reference Miyauchi H, Osokawa H, Akaeda T, Hitoki I, Asada Y. T-cell subsets in toxic epidermal necrolysis. Possible pathogenic mechanism induced by CD8-positive T cells. Arch Dermatol. 1991;127:851–5.CrossRefPubMed Miyauchi H, Osokawa H, Akaeda T, Hitoki I, Asada Y. T-cell subsets in toxic epidermal necrolysis. Possible pathogenic mechanism induced by CD8-positive T cells. Arch Dermatol. 1991;127:851–5.CrossRefPubMed
5.
go back to reference Correia O, Delgado L, Ramos JP, Resende C, Torrinha JA. Cutaneous T-cell recruitment in toxic epidermal necrolysis. Further evidence of CD8+ lymphocyte involvement. Arch Dermatol. 1993;129:466–8.CrossRefPubMed Correia O, Delgado L, Ramos JP, Resende C, Torrinha JA. Cutaneous T-cell recruitment in toxic epidermal necrolysis. Further evidence of CD8+ lymphocyte involvement. Arch Dermatol. 1993;129:466–8.CrossRefPubMed
6.
go back to reference Le Cleach L, Delaire S, Boumsell L, Bagot M, Bourgault-Villada I, Bensussan A, et al. Blister fluid T lymphocytes during toxic epidermal necrolysis are functional cytotoxic cells which express human natural killer (NK) inhibitory receptors. Clin Exp Immunol. 2000;119:225–30.CrossRefPubMedPubMedCentral Le Cleach L, Delaire S, Boumsell L, Bagot M, Bourgault-Villada I, Bensussan A, et al. Blister fluid T lymphocytes during toxic epidermal necrolysis are functional cytotoxic cells which express human natural killer (NK) inhibitory receptors. Clin Exp Immunol. 2000;119:225–30.CrossRefPubMedPubMedCentral
7.
go back to reference Nassif A, Bensussan A, Dorothée G, Mami-Chouaib F, Bachot N, Bagot M, et al. Drug specific cytotoxic T-cells in the skin lesions of a patient with toxic epidermal necrolysis. J Invest Dermatol. 2002;118:728–33.CrossRefPubMed Nassif A, Bensussan A, Dorothée G, Mami-Chouaib F, Bachot N, Bagot M, et al. Drug specific cytotoxic T-cells in the skin lesions of a patient with toxic epidermal necrolysis. J Invest Dermatol. 2002;118:728–33.CrossRefPubMed
8.
go back to reference Su SC, Chung WH. Cytotoxic proteins and therapeutic targets in severe cutaneous adverse reactions. Toxins (Basel). 2014;6:194–210.CrossRef Su SC, Chung WH. Cytotoxic proteins and therapeutic targets in severe cutaneous adverse reactions. Toxins (Basel). 2014;6:194–210.CrossRef
9.
go back to reference Morales J, Homey B, Vicari AP, Hudak S, Oldham E, Hedrick J, et al. CTACK, a skin-associated chemokine that preferentially attracts skin-homing memory T cells. Proc Natl Acad Sci USA. 1999;96:14470–5.CrossRefPubMedPubMedCentral Morales J, Homey B, Vicari AP, Hudak S, Oldham E, Hedrick J, et al. CTACK, a skin-associated chemokine that preferentially attracts skin-homing memory T cells. Proc Natl Acad Sci USA. 1999;96:14470–5.CrossRefPubMedPubMedCentral
10.
go back to reference Martinez-Rodriguez M, Thompson AK, Monteagudo C. High CCL27 immunoreactivity in ‘supratumoral’ epidermis correlates with better prognosis in patients with cutaneous malignant melanoma. J Clin Pathol. 2017;70:15–9.CrossRefPubMed Martinez-Rodriguez M, Thompson AK, Monteagudo C. High CCL27 immunoreactivity in ‘supratumoral’ epidermis correlates with better prognosis in patients with cutaneous malignant melanoma. J Clin Pathol. 2017;70:15–9.CrossRefPubMed
11.
go back to reference Homey B, Alenius H, Müller A, Soto H, Bowman EP, Yuan W, et al. CCL27–CCR10 interactions regulate T cell-mediated skin inflammation. Nat Med. 2002;8:157–65.CrossRefPubMed Homey B, Alenius H, Müller A, Soto H, Bowman EP, Yuan W, et al. CCL27–CCR10 interactions regulate T cell-mediated skin inflammation. Nat Med. 2002;8:157–65.CrossRefPubMed
12.
go back to reference Hudak S, Hagen M, Liu Y, Catron D, Oldham E, McEvoy LM, et al. Immune surveillance and effector functions of CCR10 + skin homing T cells. J Immunol. 2002;169:1189–96.CrossRefPubMed Hudak S, Hagen M, Liu Y, Catron D, Oldham E, McEvoy LM, et al. Immune surveillance and effector functions of CCR10 + skin homing T cells. J Immunol. 2002;169:1189–96.CrossRefPubMed
13.
go back to reference Tapia B, Padial A, Sánchez-Sabaté E, Alvarez-Ferreira J, Morel E, Blanca M, et al. Involvement of CCL27–CCR10 interactions in drug-induced cutaneous reactions. J Allergy Clin Immunol. 2004;114:335–40.CrossRefPubMed Tapia B, Padial A, Sánchez-Sabaté E, Alvarez-Ferreira J, Morel E, Blanca M, et al. Involvement of CCL27–CCR10 interactions in drug-induced cutaneous reactions. J Allergy Clin Immunol. 2004;114:335–40.CrossRefPubMed
14.
go back to reference Vestergaard C, Johansen C, Otkjaer K, Deleuran M, Iversen L. Tumor necrosis factor-alpha-induced CTACK/CCL27 (cutaneous T-cell-attracting chemokine) production in keratinocytes is controlled by nuclear factor kappaB. Cytokine. 2005;29:49–55.CrossRefPubMed Vestergaard C, Johansen C, Otkjaer K, Deleuran M, Iversen L. Tumor necrosis factor-alpha-induced CTACK/CCL27 (cutaneous T-cell-attracting chemokine) production in keratinocytes is controlled by nuclear factor kappaB. Cytokine. 2005;29:49–55.CrossRefPubMed
15.
go back to reference Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine. 2015;74:5–17.CrossRefPubMed Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine. 2015;74:5–17.CrossRefPubMed
17.
go back to reference Chávez-Galán L, Arenas-Del Angel MC, Zenteno E, Chávez R, Lascurain R. Cell death mechanisms induced by cytotoxic lymphocytes. Cell Mol Immunol. 2009;6:15–25.CrossRefPubMedPubMedCentral Chávez-Galán L, Arenas-Del Angel MC, Zenteno E, Chávez R, Lascurain R. Cell death mechanisms induced by cytotoxic lymphocytes. Cell Mol Immunol. 2009;6:15–25.CrossRefPubMedPubMedCentral
18.
go back to reference Norman MU, Lister KJ, Yang YH, Issekutz A, Hickey MJ. TNF regulates leukocyte–endothelial cell interactions and microvascular dysfunction during immune complex-mediated inflammation. Br J Pharmacol. 2005;144:265–74.CrossRefPubMedPubMedCentral Norman MU, Lister KJ, Yang YH, Issekutz A, Hickey MJ. TNF regulates leukocyte–endothelial cell interactions and microvascular dysfunction during immune complex-mediated inflammation. Br J Pharmacol. 2005;144:265–74.CrossRefPubMedPubMedCentral
19.
go back to reference Caproni M, Torchia D, Schincaglia E, Volpi W, Frezzolini A, Schena D, et al. Expression of cytokines and chemokine receptors in the cutaneous lesions of erythema multiforme and Stevens–Johnson syndrome/toxic epidermal necrolysis. Br J Dermatol. 2006;155:722–8.CrossRefPubMed Caproni M, Torchia D, Schincaglia E, Volpi W, Frezzolini A, Schena D, et al. Expression of cytokines and chemokine receptors in the cutaneous lesions of erythema multiforme and Stevens–Johnson syndrome/toxic epidermal necrolysis. Br J Dermatol. 2006;155:722–8.CrossRefPubMed
20.
go back to reference Wang F, He D, Tang X, Zhang X. Chemokine expression in diverse nonimmediate drug hypersensitivity reactions: focus on thymus activation-regulated chemokine, cutaneous T-cell-attracting chemokine, and interleukin-10. Ann Allergy Asthma Immunol. 2014;113:204–8.CrossRefPubMed Wang F, He D, Tang X, Zhang X. Chemokine expression in diverse nonimmediate drug hypersensitivity reactions: focus on thymus activation-regulated chemokine, cutaneous T-cell-attracting chemokine, and interleukin-10. Ann Allergy Asthma Immunol. 2014;113:204–8.CrossRefPubMed
21.
go back to reference Wang F, Cai R, He D, Zhao Y, Ye Y, Zhang X. Serum IFN-γ-inducible chemokines CXCL9 and CXCL10 are elevated in non-immediate drug hypersensitivity reactions. Asian Pac J Allergy Immunol. 2016;34:236–41.PubMed Wang F, Cai R, He D, Zhao Y, Ye Y, Zhang X. Serum IFN-γ-inducible chemokines CXCL9 and CXCL10 are elevated in non-immediate drug hypersensitivity reactions. Asian Pac J Allergy Immunol. 2016;34:236–41.PubMed
22.
go back to reference Edwards IR, Aronson JK. Adverse drug reactions: defnitions, diagnosis and management. Lancet. 2000;356:1255–9.CrossRefPubMed Edwards IR, Aronson JK. Adverse drug reactions: defnitions, diagnosis and management. Lancet. 2000;356:1255–9.CrossRefPubMed
23.
go back to reference van den Broek LJ, Kroeze KL, Waaijman T, Breetveld M, Sampat-Sardjoepersad SC, Niessen FB, et al. Differential response of human adipose tissue-derived mesenchymal stem cells, dermal fibroblasts, and keratinocytes to burn wound exudates: potential role of skin-specific chemokine CCL27. Tissue Eng Part A. 2014;20:197–209.CrossRefPubMed van den Broek LJ, Kroeze KL, Waaijman T, Breetveld M, Sampat-Sardjoepersad SC, Niessen FB, et al. Differential response of human adipose tissue-derived mesenchymal stem cells, dermal fibroblasts, and keratinocytes to burn wound exudates: potential role of skin-specific chemokine CCL27. Tissue Eng Part A. 2014;20:197–209.CrossRefPubMed
24.
go back to reference Paquet P, Paquet F, Al Saleh W, Reper P, Vanderkelen A, Piérard GE. Immunoregulatory effector cells in drug-induced toxic epidermal necrolysis. Am J Dermatopathol. 2000;22:413–7.CrossRefPubMed Paquet P, Paquet F, Al Saleh W, Reper P, Vanderkelen A, Piérard GE. Immunoregulatory effector cells in drug-induced toxic epidermal necrolysis. Am J Dermatopathol. 2000;22:413–7.CrossRefPubMed
25.
go back to reference Posadas SJ, Padial A, Torres MJ, Mayorga C, Leyva L, Sanchez E, et al. Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity. J Allergy Clin Immunol. 2002;109:155–61.CrossRefPubMed Posadas SJ, Padial A, Torres MJ, Mayorga C, Leyva L, Sanchez E, et al. Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity. J Allergy Clin Immunol. 2002;109:155–61.CrossRefPubMed
26.
go back to reference Su SC, Mockenhaupt M, Wolkenstein P, Dunant A, Le Gouvello S, Chen CB, et al. Interleukin-15 is associated with severity and mortality in stevens–johnson syndrome/toxic epidermal necrolysis. J Invest Dermatol. 2017;137:1065–73.CrossRefPubMed Su SC, Mockenhaupt M, Wolkenstein P, Dunant A, Le Gouvello S, Chen CB, et al. Interleukin-15 is associated with severity and mortality in stevens–johnson syndrome/toxic epidermal necrolysis. J Invest Dermatol. 2017;137:1065–73.CrossRefPubMed
27.
go back to reference Nomura Y, Aihara M, Matsukura S, Ikezawa Y, Kambara T, Aihara Y, et al. Evaluation of serum cytokine levels in toxic epidermal necrolysis and Stevens–Johnson syndrome compared with other delayed-type adverse drug reactions. J Dermatol. 2011;38(11):1076–9.CrossRefPubMed Nomura Y, Aihara M, Matsukura S, Ikezawa Y, Kambara T, Aihara Y, et al. Evaluation of serum cytokine levels in toxic epidermal necrolysis and Stevens–Johnson syndrome compared with other delayed-type adverse drug reactions. J Dermatol. 2011;38(11):1076–9.CrossRefPubMed
28.
go back to reference Viard-Leveugle I, Gaide Jankovic D, Feldmeyer L, Kerl K, Pickard C, et al. TNF-α and IFN-γ are potential inducers of Fas-mediated keratinocyte apoptosis through activation of inducible nitric oxide synthase in toxic epidermal necrolysis. J Invest Dermatol. 2013;133:489–98.CrossRefPubMed Viard-Leveugle I, Gaide Jankovic D, Feldmeyer L, Kerl K, Pickard C, et al. TNF-α and IFN-γ are potential inducers of Fas-mediated keratinocyte apoptosis through activation of inducible nitric oxide synthase in toxic epidermal necrolysis. J Invest Dermatol. 2013;133:489–98.CrossRefPubMed
29.
go back to reference Paradisi A, Abeni D, Bergamo F, Ricci F, Didona D, Didona B. Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol. 2014;71:278–83.CrossRefPubMed Paradisi A, Abeni D, Bergamo F, Ricci F, Didona D, Didona B. Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol. 2014;71:278–83.CrossRefPubMed
30.
go back to reference Napolitano M, Giampetruzzi AR, Didona D, Papi M, Didona B. Toxic epidermal necrolysis-like acute cutaneous lupus erythematosus successfully treated with a single dose of etanercept: report of three cases. J Am Acad Dermatol. 2013;69:e303–5.CrossRefPubMed Napolitano M, Giampetruzzi AR, Didona D, Papi M, Didona B. Toxic epidermal necrolysis-like acute cutaneous lupus erythematosus successfully treated with a single dose of etanercept: report of three cases. J Am Acad Dermatol. 2013;69:e303–5.CrossRefPubMed
31.
go back to reference Gubinelli E, Canzona F, Tonanzi T, Raskovic D, Didona B. Toxic epidermal necrolysis successfully treated with etanercept. J Dermatol. 2009;36:150–3.CrossRefPubMed Gubinelli E, Canzona F, Tonanzi T, Raskovic D, Didona B. Toxic epidermal necrolysis successfully treated with etanercept. J Dermatol. 2009;36:150–3.CrossRefPubMed
Metadata
Title
Diverse expression of TNF-α and CCL27 in serum and blister of Stevens–Johnson syndrome/toxic epidermal necrolysis
Authors
Fang Wang
Yanting Ye
Ze-Yu Luo
Qian Gao
Di-Qing Luo
Xingqi Zhang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Clinical and Translational Allergy / Issue 1/2018
Electronic ISSN: 2045-7022
DOI
https://doi.org/10.1186/s13601-018-0199-6

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