Elevated serum levels of epithelial cell apoptosis-specific cytokeratin 18 neoepitope m30 in critically ill patients.
Apoptosis of the epithelium is deemed to play a pivotal role in the pathogenesis of sepsis. A neoepitope in cytokeratin 18 (CK18), termed M30 neoantigen, becomes available at an early caspase cleavage event during apoptosis of epithelium-derived cells and is not detectable in vital or necrotic epithelial cells. A monoclonal antibody, M30, specifically recognizes a fragment of CK18 cleaved at Asp396 (M30 neoantigen). We used an enzyme-linked immunosorbent assay (ELISA) to measure M30 antigen levels in the sera of 15 septic patients. Healthy humans and critical ill patients suffering from severe trauma served as controls. Mann-Whitney U test was used to calculate significance, and a P value of <0.01 was considered to be statistically significant. Serum levels of the CK18 neoepitope M30 were significantly increased in septic patients (236.88 +/- 47.4 U/L) versus trauma (97.2 +/- 17.1 U/L) and healthy controls (66.9 +/- 9.2 U/L) (P < 0.01 and P < 0.008, respectively). The increased serum level of the CK18 neoepitope in septic patients indicates a heightened apoptotic turnover in epithelial cells as compared with trauma patients and healthy controls. Interestingly, nonsurviving trauma patients exhibited a significant increase in the M30 neoantigen as compared with survivors and healthy controls (P < 0.003 and P < 0.002, respectively). The detection of CK18 neoepitope M30 in the serum might be a useful marker in tracing apoptotic epithelium in septic patients.
Department of Surgery, General Hospital, Vienna Medical School, Vienna, Austria.
Georg Alexander
GA
Roth
Claus
C
Krenn
Markus
M
Brunner
Bernhard
B
Moser
Martin
M
Ploder
Andreas
A
Spittler
Linda
L
Pelinka
Thomas
T
Sautner
Ernst
E
Wolner
George
G
Boltz-Nitulescu
Hendrik J
HJ
Ankersmit
D000328:Adult; D015415:Biomarkers / Q000097:blood; D000939:Epitopes / Q000097:blood*; D005260:Female; D006801:Humans; D007633:Keratins / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012189:Retrospective Studies; D018805:Sepsis / Q000097:blood*; D014947:Wounds and Injuries / Q000097:blood*
D015415:Biomarkers; D000939:Epitopes; D007633:Keratins