title: Immunohistochemical expression of activated caspase-3 as a marker of apoptosis in glomeruli of human lupus nephritis.
abstract: BACKGROUND
  The role of apoptosis in lupus nephritis (LN) is still controversial. One of the key events in the process of apoptosis is activation of caspase-3. Studies of experimental models suggested that activated caspase-3 is a reliable indicator of apoptotic rate, with a favorable comparison against terminal transferase-mediated DNA nick-end labeling (TUNEL) assay. Our aim is to study apoptosis in various forms of LN and its relationship to histomorphological changes and selected laboratory findings by using activated caspase-3 as a novel marker of apoptosis.
  
  
  METHODS
  We investigated glomerular cell apoptosis in 51 biopsy specimens from patients with LN classified according to the International Society of Nephrology/Renal Pathology Society classification by using the TUNEL method and immunohistochemistry against activated caspase-3. In addition, activity and chronicity indices were calculated and anti-Ki-67 antibody was used to estimate proliferative activity.
  
  
  RESULTS
  Activated caspase-3-positive cells were present in glomeruli of 88.2% of cases, observed in the glomerular tuft and cellular and fibrocellular crescents. In the glomerular tuft, they were found mainly in segments with active inflammatory lesions. There was good correlation between apoptotic index assessed by using activated caspase-3 immunolabeling and the TUNEL method (r = 0.72; P < 0.01). We observed a significant positive correlation between apoptotic index and LN class (P < 0.001). Apoptotic index correlated significantly with activity index, proliferation index, and daily protein excretion (P < 0.001), but not chronicity index, creatinine concentration, or anti-DNA antibody-binding activity in serum.
  
  
  CONCLUSIONS
  Apoptotic rate is greater in severe active glomerular lesions in human LN, suggesting that apoptosis may be involved in augmenting inflammation in human LN.
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Ljubljana, Slovenia. jera.jeruc@mf.uni-lj.si
authors.forename: Jera
authors.initials: J
authors.lastname: Jeruc
authors.forename: Alenka
authors.initials: A
authors.lastname: Vizjak
authors.forename: Blaz
authors.initials: B
authors.lastname: Rozman
authors.forename: Dusan
authors.initials: D
authors.lastname: Ferluga
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D015415:Biomarkers; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002648:Child; D004789:Enzyme Activation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D008181:Lupus Nephritis / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases