Circulating nucleosomes as predictive markers of severe acute pancreatitis

Anne K. Penttilä, Ari Rouhiainen, Leena Kylänpää, Harri Mustonen, Pauli Puolakkainen, Heikki Rauvala, Heikki Repo

The components of nucleosomes, which contain DNA and histones, are released into the circulation from damaged cells and can promote inflammation. We studied whether the on-admission levels of circulating nucleosomes predict the development of severe acute pancreatitis (AP), in particular among the patients who present without clinical signs of organ dysfunction. This is a prospective study of 74 AP patients admitted to Helsinki University Hospital from 2003 to 2007. Twenty-three patients had mild, 27 moderately severe, and 24 severe AP as defined by the revised Atlanta criteria. 14/24 severe AP patients had no sign of organ dysfunction on admission (modified marshall score <2). Blood samples were obtained on admission and the plasma levels of nucleosomes were measured using enzyme-linked immunosorbent assay. The on-admission levels of nucleosomes were significantly higher in severe AP than in mild or moderately severe AP (p < 0.001 for all), higher in non-survivors (n = 8) than in survivors (p = 0.019), and correlated with the on-admission levels of C-reactive protein (p < 0.001) and creatinine (p < 0.001). Among the AP patients who presented without organ dysfunction, the on-admission nucleosome level was an independent predictor of severe AP (p = 0.038, gender-adjusted forward-stepping logistic regression). Circulating nucleosome levels may be helpful in identifying, on admission to hospital, the AP patients who present without clinical signs of organ dysfunction, and, yet, are bound to develop organ dysfunction during hospitalization.