title: Apoptosis of keratinocytes and serum DNase I activity in patients with cutaneous lupus erythematosus: relationship with clinical and immunoserological parameters.
abstract: BACKGROUND
  Dysregulation of apoptosis has an important role in the induction of autoimmunity.
  
  
  OBJECTIVE
  To evaluate the influence of keratinocyte apoptosis and deoxyribonuclease I (DNase I) activity on the clinical and immunoserological parameters of cutaneous lupus erythematosus (CLE).
  
  
  METHODS
  We studied 69 CLE patients (39 with discoid LE (DLE), 12 with subacute CLE (SCLE), 12 with acute and 6 with intermittent CLE). Thirty of sixty-nine patients fulfilled criteria for systemic LE (SLE). Apoptotic index (AI) was evaluated immunohistochemically in lesional and non-lesional, photoprotected skin. Serum DNase I activity, antichromatin and anti-ENA antibodies were measured by ELISA. Disease activity was determined by SLEDAI-2K, SLICC/ACR, CLASI and RCLASI.
  
  
  RESULTS
  AI in lesions was higher than in non-lesional skin (P < 0.001). There was no difference in AI between CLE and SLE patients. Patients with SCLE had higher lesional AI than patients with DLE (P < 0.05). We found a positive correlation between the lesional AI with CLASI A (P < 0.05) and RCLASI D (P < 0.05). CLE and SLE patients had significantly lower DNase I activity than healthy controls (P < 0.001). Patients with normal DNase I activity and low AI had significantly lower CLASI A than patients with decreased DNase I activity and/or elevated AI (P < 0.05).
  
  
  CONCLUSIONS
  Increased keratinocyte apoptosis characterizes lesions of all CLE forms, especially of SCLE. AI correlates with CLE markers of acute and chronic inflammation. Normal level of apoptosis and DNase I activity simultaneously reduce the level of acute inflammation in CLE. Serum DNase I activity and AI might be important biomarkers in the evaluation of CLE patients.
authors.affiliation: Department of Dermatovenereology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Skiljevic
authors.affiliation: Department of Allergy and Clinical Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: B
authors.initials: B
authors.lastname: Bonaci-Nikolic
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Brasanac
authors.affiliation: Department of Dermatovenereology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: M
authors.initials: M
authors.lastname: Nikolic
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood; D034961:Antigens, Nuclear / Q000097:blood; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D003850:Deoxyribonuclease I / Q000097:blood*; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000502:physiology; D008178:Lupus Erythematosus, Cutaneous / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology*; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D012879:Skin Physiological Phenomena; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D034961:Antigens, Nuclear; D015415:Biomarkers; D003850:Deoxyribonuclease I