Mucins carrying selectin ligands as predictive biomarkers of disseminated intravascular coagulation complication in ARDS.
BACKGROUND
ARDS patients present with intrapulmonary and systemic coagulation abnormalities. We previously demonstrated that circulating KL-6/MUC1 could predict complications of disseminated intravascular coagulation (DIC) in ARDS. Recent studies indicate that circulating mucin can induce intravascular coagulation via interactions with selectin. We, therefore, investigated whether circulating mucins carrying selectin ligands are associated with DIC in ARDS.


METHODS
We evaluated newly diagnosed patients with ARDS (n = 46) or bacterial pneumonia (n = 17), and healthy control subjects (n = 60). Using serum collected at diagnosis, circulating levels of KL-6/MUC1, KL-6/MUC1 carrying sialyl Lewis(a) (SLAK), KL-6/MUC1 carrying sialyl Lewis(x) (SLXK), and P-selectin glycoprotein ligand-1 (PSGL-1) were measured.


RESULTS
Serum mucins with selectin ligands were significantly elevated in patients with ARDS compared with healthy control subjects. Significantly elevated levels of SLAK and SLXK were found in patients with ARDS subsequently complicated with DIC, as compared with those without DIC. In contrast, serum PSGL-1 levels were significantly decreased in ARDS patients with DIC. Furthermore, SLAK was discovered to be an independent predictor of DIC complication in ARDS. Using cutoff levels obtained by receiver operating characteristic curves, we found that these mucins can be used to distinguish between patients with ARDS with and without subsequently occurring DIC. Among the analyzed mucins, SLAK has the highest sensitivity and specificity for predicting future DIC development.


CONCLUSIONS
These results suggest that mucins with selectin ligands are novel markers for ARDS with future complications of DIC, and KL-6/MUC1 carrying selectin ligands may be involved in the pathogenesis of DIC in patients with ARDS.
Nakashima
Taku
T
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Yokoyama
Akihito
A
Department of Hematology and Respiratory Medicine, Kochi University, Kochi, Japan. Electronic address: ayokoyama@kochi-u.ac.jp.
Inata
Jyunya
J
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Ishikawa
Nobuhisa
N
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Haruta
Yoshinori
Y
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Hattori
Noboru
N
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Kohno
Nobuoki
N
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D009077:Mucins / Q000097:blood*; D019007:P-Selectin / Q000097:blood*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000150:complications; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D015415:Biomarkers; D008024:Ligands; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; D019007:P-Selectin