The six most intense peptides were fragmented, and the MS1 spectra were acquired at a resolution of 60,000. Data mining was performed against the rat UniProtKB data bank, using Proteome

Discoverer 1.1 software (Thermo Instruments), with an accuracy of less than 5 ppm for parent ions and 0.8 Da for fragments. All the proteins thus identified were analyzed using Pantherd software to determine their gene ontology parameters. Biological and histological features of the patients at the diagnosis of acute hepatitis are reported in Table 1. Mean values for total bilirubin, gamma-glutamyl transferase (GGT), and aminoaspartate transferase (AST) levels, as well as the prothrombin time, were, respectively, 121 µmol/L (range, 29-270), 933 IU/L (range, 455-1,968), 1,438 IU/L (range, 538–2,900), and 74% (range, 37-100). IgG levels were KU-60019 order high in P1 (24.5 g/L) and P5 (24.4 g/L), but normal in the other patients. Pathological examination revealed features of acute hepatitis with interface (n = 4) and lobular (n = 4) necroinflammatory activity. An abundant inflammatory infiltrate, including plasmocytes, was present in three patients (P1, P3 and P5) (Fig. 1). During the initial presentation, fibrosis selleck inhibitor was mild or absent in P1, P3, P4 and P5, and advanced in P2. There was no evidence of pathological features of GVHD or veno-occlusive disease. Moreover, at the onset of liver

dysfunction, no extrahepatic symptoms suggestive of GVHD could be detected. In the control groups, the histological pattern of acetaminophen hepatitis differed markedly from

the pattern described above (Supporting Fig. 1). Necrosis was the sole feature observed, without any lymphoplasmocytic infiltrate. With respect SDHB to autoantibody detection, no patient was positive for anti-SMA, anti-LKM1, or anti-LC1 before and at the onset of hepatic dysfunction. ANA were negative in all patients before hepatic disease and remained negative in P1, P4, and P5, although becoming positive in P2 and P3 (1:80 and 1:640, respectively). All viral markers tested, namely HAV, HBV, HCV, HEV, CMV, EBV, HHV6, and HSV, were negative in patients P2, P3, P4, and P5 before BMT and remained so after the onset of hepatic dysfunction. In P1, although the HCV test was positive before BMT, no HCV RNA could be detected by PCR. Immunoblottings performed on cellular fractions displayed very few common stained bands between patients P1-P3 and the two control groups (Supporting Fig. 2). A comparison of 2D immunoblotting patterns showed that immunoreactive spots were more numerous and more intensely stained by the three sera collected at the onset of the hepatic dysfunction than by those collected before, regardless of the type of liver subfraction used as the antigen (Fig. 2). Moreover, a marked patient-related heterogeneity of the patterns was noted (Fig. 3). A total of 259 spots only present at the time of onset of liver dysfunction were detected (Supporting Fig.