Research Article
Accumulation of apoptotic cells in the epidermis of patients with cutaneous lupus erythematosus after ultraviolet irradiation
Annegret Kuhn,
Martin Herrmann, Susanne Kleber,
Maria Beckmann-Welle,
Karin Fehsel, Ana Martin-Villalba,
Percy Lehmann, Thomas Ruzicka, Peter H. Krammer,
Victoria Kolb-Bachofen,
Corresponding Author
Annegret Kuhn
University of Düsseldorf, Dusseldorf, and the German Cancer Research Center, Heidelberg, Germany
Tumor Immunology Program, Division of Immunogenetics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, GermanySearch for more papers by this authorSusanne Kleber
German Cancer Research Center, Heidelberg, Germany
Search for more papers by this authorMaria Beckmann-Welle
University of Düsseldorf, Dusseldorf, Germany
Search for more papers by this authorAna Martin-Villalba
German Cancer Research Center, Heidelberg, Germany
Search for more papers by this authorPeter H. Krammer
German Cancer Research Center, Heidelberg, Germany
Search for more papers by this authorVictoria Kolb-Bachofen
University of Düsseldorf, Dusseldorf, Germany
Search for more papers by this authorAnnegret Kuhn,
Martin Herrmann, Susanne Kleber,
Maria Beckmann-Welle,
Karin Fehsel, Ana Martin-Villalba,
Percy Lehmann, Thomas Ruzicka, Peter H. Krammer,
Victoria Kolb-Bachofen,
Corresponding Author
Annegret Kuhn
University of Düsseldorf, Dusseldorf, and the German Cancer Research Center, Heidelberg, Germany
Tumor Immunology Program, Division of Immunogenetics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, GermanySearch for more papers by this authorSusanne Kleber
German Cancer Research Center, Heidelberg, Germany
Search for more papers by this authorMaria Beckmann-Welle
University of Düsseldorf, Dusseldorf, Germany
Search for more papers by this authorAna Martin-Villalba
German Cancer Research Center, Heidelberg, Germany
Search for more papers by this authorPeter H. Krammer
German Cancer Research Center, Heidelberg, Germany
Search for more papers by this authorVictoria Kolb-Bachofen
University of Düsseldorf, Dusseldorf, Germany
Search for more papers by this authorAbstract
Objective
To examine whether apoptosis contributes to the pathogenesis of skin lesions in patients with cutaneous lupus erythematosus (CLE) after ultraviolet (UV) irradiation.
Methods
In situ nick translation and TUNEL were performed to detect apoptosis in 85 skin biopsy specimens from patients with various subtypes of CLE. Specimens from normal healthy donors and patients with polymorphous light eruption were used as controls. In addition to assessment of primary lesions, provocative phototesting was carried out to investigate events occurring secondary to UV irradiation during a very early stage of lesion formation.
Results
A significant increase in apoptotic nuclei was found in the upper epidermal layer of primary and UV light–induced skin lesions of CLE patients compared with controls. In tissue sections obtained from control subjects at 24 hours after a single exposure to UV light, a slight increase in the count of epidermal apoptotic nuclei was present as compared with skin tissue from CLE patients obtained under the same conditions before lesion formation. In sections obtained from controls at 72 hours after irradiation, a significant decrease in the apoptotic nuclei count was observed, consistent with a proper clearance of apoptotic cells in the period between 24 and 72 hours after irradiation. In striking contrast, the number of apoptotic nuclei increased significantly within this period in tissue sections from patients with CLE.
Conclusion
These data support the hypothesis that apoptotic cells accumulate in the skin of patients with CLE after UV irradiation, as a result of impaired or delayed clearance. The nonengulfed cells may undergo secondary necrosis and release proinflammatory compounds and potential autoantigens, which may contribute to the inflammatory micromilieu that leads to formation of skin lesions in this disease.
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