Is disturbed clearance of apoptotic keratinocytes responsible for UVB-induced inflammatory skin lesions in systemic lupus erythematosus?
Apoptotic cells are thought to play an essential role in the pathogenesis of systemic lupus erythematosus (SLE). We hypothesise that delayed or altered clearance of apoptotic cells after UV irradiation will lead to inflammation in the skin of SLE patients. Fifteen SLE patients and 13 controls were irradiated with two minimal erythemal doses (MEDs) of ultraviolet B light (UVB). Subsequently, skin biopsies were analysed (immuno)histologically, over 10 days, for numbers of apoptotic cells, T cells, macrophages, and deposition of immunoglobulin and complement. Additionally, to compare results with cutaneous lesions of SLE patients, 20 biopsies of lupus erythematosus (LE) skin lesions were analysed morphologically for apoptotic cells and infiltrate. Clearance rate of apoptotic cells after irradiation did not differ between patients and controls. Influx of macrophages in dermal and epidermal layers was significantly increased in patients compared with controls. Five out of 15 patients developed a dermal infiltrate that was associated with increased epidermal influx of T cells and macrophages but not with numbers of apoptotic cells or epidermal deposition of immunoglobulins. Macrophages were ingesting multiple apoptotic bodies. Inflammatory lesions in these patients were localised near accumulations of apoptotic keratinocytes similar as was seen in the majority of LE skin lesions. In vivo clearance rate of apoptotic cells is comparable between SLE patients and controls. However, the presence of inflammatory lesions in the vicinity of apoptotic cells, as observed both in UVB-induced and in LE skin lesions in SLE patients, suggests that these lesions result from an inflammatory clearance of apoptotic cells.
Reefman
Esther
E
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, PO Box 30,001, 9700 RB Groningen, The Netherlands. e.reefman@med.umcg.nl
de Jong
Marcelus C J M
MC
Kuiper
Hilde
H
Jonkman
Marcel F
MF
Limburg
Pieter C
PC
Kallenberg
Cees G M
CG
Bijl
Marc
M
D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood; D017209:Apoptosis / Q000528:radiation effects*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D015603:Keratinocytes / Q000473:pathology / Q000528:radiation effects*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000209:etiology / Q000473:pathology; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D012871:Skin Diseases / Q000209:etiology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000974:Antibodies, Antinuclear