Skip to main content
SpringerLink
Log in

DNA damage in human skin fibroblasts from patients with dermatitis herpetiformis

  • Investigative Report
  • Published:
European Journal of Dermatology

Abstract

Background

Dermatitis herpetiformis (DH) and celiac disease (CD) are considered to be autoimmune diseases that share a specific trigger (gluten) and a common genetic background (HLA-DQ2/DQ8). However, the pathogenesis of DH is not yet fully understood and no data are available regarding a possible role of fibroblasts in this disease.

Objectives

The aim of this study was to assess baseline DNA damage in fibroblasts in DH-diagnosed patients vs. fibroblasts of controls without DH or CD.

Materials and Methods

Primary fibroblast cultures were derived from dermal biopsies from DH patients and controls (without DH or CD). In vitro genotoxic damage was investigated using the comet assay and γH2AX test after different treatments (with 33mer peptide and digested gliadin [DG]) in order to investigate a correlation between oxidative stress (evaluated by reactive oxygen species formation) and glutathione content.

Results

Our results demonstrate a difference in baseline DNA damage between cutaneous fibroblasts of controls and DH patients, moreover, DNA damage significantly increased after exposure to gluten (DG and 33mer peptide) in fibroblasts from DH patients. DNA damage in fibroblasts from patients under dapsone treatment was similar to that of the control group.

Conclusion

Our data indicate that oxidative stress and DNA damage may be characteristics of fibroblasts from DH patients who are not treated with dapsone, particularly after exposure to gliadin peptides.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Collin P, Salmi TT, Hervonen K, Kaukinen K, Reunala T. Dermatitis herpetiformis: a cutaneous manifestation of coeliac disease. Ann Med 2017; 49:23–31.

    Article  CAS  PubMed  Google Scholar 

  2. Bonciani D, Verdelli A, Bonciolini V, et al. dermatitis herpetiformis: from the genetics to the development of skin lesions. Clin Dev Immunol 2012; 2012:7.

    Article  CAS  Google Scholar 

  3. Hietikko M, Hervonen K, Ilus T, et al. Ex vivo Culture of duodenal biopsies from patients with dermatitis herpetiformis indicates that transglutaminase 3 antibody production occurs in the gut. Acta Derm Venereol 2018; 98:366–72.

    Article  CAS  PubMed  Google Scholar 

  4. Mendes FBR, Hissa-Elian A, De Abreu M, Scaff Gonc¸alves V. Review: dermatitis herpetiformis. An Bras Dermatol 2013; 88:594–9.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Herrera MG, Benedini LA, Lonez C, et al. Self-assembly of 33-mer gliadin peptide oligomers. Soft Matter 2015; 11:8648–60.

    Article  CAS  PubMed  Google Scholar 

  6. Paolella G, Lepretti M, Barone V, et al. Celiac anti-type 2 trans-glutaminase antibodies induce differential effects in fibroblasts from celiac disease patients and from healthy subjects. Amino Acids 2017; 49:541–50.

    Article  CAS  PubMed  Google Scholar 

  7. Qiao S, Bergseng E, Molberg O, et al. Antigen presentation to celiac lesion-derived T cells of a 33-mer gliadin peptide naturally formed by gastrointestinal digestion. J Immunol 2017; 173:1757–62.

    Article  Google Scholar 

  8. Berroth A, Kühnl J, Kurschat N, et al. Role of fibroblasts in the pathogenesis of atopic dermatitis. J Allergy Clin Immunol 2013; 131:1547–54.

    Article  CAS  PubMed  Google Scholar 

  9. Clarindo MV, Soligo EM, Ruaro RT. Presentation diagnosis and treatment. An Bras Dermatol 2014; 89:865–77.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Salmi TT, Hervonen K, Kurppa K, Collin P, Kaukinen K, Reunala T. Celiac disease evolving into dermatitis herpetiformis in patients adhering to normal or gluten-free diet. Scand J Gastroenterol 2015; 50:387–92.

    Article  CAS  PubMed  Google Scholar 

  11. Reunala T, Salmi TT, Hervonen K, et al. IgA antiepidermal transglutaminase antibodies in dermatitis herpetiformis: a significant but not complete response to a gluten-free diet treatment. Brit J Dermatol 2015; 172:1139–41.

    Article  CAS  Google Scholar 

  12. Kotze L. Review: dermatitis herpetiformis. Arq Gastroenterol 2013; 50:231–5.

    Article  PubMed  Google Scholar 

  13. Kelly C, Bai J, Edwin L, Leffler D. Advances in diagnosis and management of celiac disease. Gastroenterology 2015; 148:1175–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Antiga E, Caproni M. The diagnosis and treatment of dermatitis herpetiformis. Clin Cosmet Investig Dermatol 2015; 8:257–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ferretti G, Bacchetti T, Masciangelo S, Saturni L. Celiac disease, inflammation and oxidative damage: a nutrigenetic approach. Nutrients 2012; 4:243–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hall RP, Takeuchi F, Benbenisty KM, Streilein RD Cutaneous endothelial cell activation in normal skin of patients with dermatitis herpetiformis associated with increased serum levels of IL-8, sE-selectin, and TNF-alpha. J Invest Dermatol 2006; 126:1331–7.

    Article  CAS  PubMed  Google Scholar 

  17. Reunala T, Salmi TT, Hervonen K. Dermatitis herpetiformis: pathognomonic transglutaminase IGA deposits in the skin and excellent prognosis on a gluten-free diet. Acta Derm Venereol 2015; 95:917–22.

    Article  CAS  PubMed  Google Scholar 

  18. Schraufstatter I, Hyslop PA, Jackson JH, Cochrane CG. Oxidantinduced DNA damage of target cells. J Clin Invest 1988; 82:1040–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Vaira V, Roncoroni L, Barisani D, et al. MicroRNA profiles in coeliac patients distinguish different clinical phenotypes and are modulated by gliadin peptides in primary duodenal fibroblasts. Clin Sci 2014; 126:417–23.

    Article  CAS  PubMed  Google Scholar 

  20. Price P, Mcmillan TJ. Use of the tetrazolium assay in measuring the response of human tumor cells to ionizing radiation. Cancer Res 1990; 50:1392–6.

    CAS  PubMed  Google Scholar 

  21. Friis S, Dabelsteen E, Sjostrom H, Noren O, Jarnum S. Gliadin uptake in human enterocytes. Differences between coelic patients in remission and control individuals. Gut 1992; 33:1487–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Widel M, Krzywon A, Gajda K, Skonieczna M, Rzeszowska-Wolny J. Induction of bystander effects by UVA, UVB, and UVC radiation in human fibroblasts and the implication of reactive oxygen species. Free Radic Biol Med 2014; 68:278–87.

    Article  CAS  PubMed  Google Scholar 

  23. Lowry OH, Rosebrough NJ, Farr AL, Randal RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193:265–75.

    CAS  PubMed  Google Scholar 

  24. Fairweather D. Autoimmune Disease: Mechanisms. Chichester: John Wiley & Sons Ltd.; Encyclopedia of Life Sciences, 2007.

    Google Scholar 

  25. Smith TJ. Insights into the role of fibroblasts in human autoimmune diseases. Clin Exp Immunol 2005; 141:388–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cardones RG, Hall RP. Pathophysiology of dermatitis herpetiformis: a model for cutaneous manifestations of gastrointestinal inflammation. Immunol Allergy Clin 2012; 32:263–74.

    Article  Google Scholar 

  27. Nicolas MEO, Krause PK, Gibson LE, Murray JA. Dermatitis her-petiformis. Int J Dermatol 2003; 42:588–600.

    Article  PubMed  Google Scholar 

  28. Görög K, Németh L, Szabó B, et al. Decreased fibrinolytic potential and morphological changes of fibrin structure in dermatitis herpetiformis. J Dermatol Sci 2016; 84:17–23.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Environmental Science and Policy, Università degli Studi di Milano, Milan, Italy

    Giulia Lombardo & Laura Marabini

  2. Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy

    Luisa Doneda & Leda Roncoroni

  3. Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Vincenza Lombardo, Alice Scricciolo, Luca Elli & Leda Roncoroni

  4. Dermatology Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Valentina Della Valle & Simona Muratori

  5. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122, Milan, Italy

    Leda Roncoroni

Authors
  1. Giulia Lombardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura Marabini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luisa Doneda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vincenza Lombardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alice Scricciolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luca Elli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Valentina Della Valle
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Simona Muratori
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Leda Roncoroni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laura Marabini.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lombardo, G., Marabini, L., Doneda, L. et al. DNA damage in human skin fibroblasts from patients with dermatitis herpetiformis. Eur J Dermatol 29, 167–173 (2019). https://doi.org/10.1684/ejd.2019.3528

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1684/ejd.2019.3528

Key words

Search

Navigation