title: Two of Them Do It Better: Novel Serum Biomarkers Improve Autoimmune Hepatitis Diagnosis.
abstract: BACKGROUND
  Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology and characterized by continuing hepatocellular inflammation and necrosis. Autoantibodies represent accessible markers to measure the adaptive immune responses in the clinical investigation. Protein microarrays have become an important tool to discriminate the disease state from control groups, even though there is no agreed-upon standard to analyze the results.
  
  
  RESULTS
  In the present study 15 sera of patients with AIH and 78 healthy donors (HD) have been tested against 1626 proteins by an in house-developed array. Using a Partial Least Squares Discriminant Analysis (PLS-DA) the resulting data interpretation led to the identification of both new and previously identified proteins. Two new proteins AHPA9419 and Chondroadherin precursor (UNQ9419 and CHAD, respectively), and previously identified candidates as well, have been confirmed in a validation phase by DELFIA assay using a new cohort of AIH patients. A receiver operating characteristic analysis was used for the evaluation of biomarker candidates. The sensitivity of each autoantigen in AIH ranged from 65 to 88%; moreover, when the combination of the two new autoantigens was analyzed, the sensitivity increased to 95%.
  
  
  CONCLUSIONS
  Our findings demonstrate that the detection of autoantibodies against the two autoantigens could improve the performance in discriminating AIH patients from control classes and in combination with previously identified autoantigens and they could be used in diagnostic/prognostic markers.
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy.
authors.forename: Saveria
authors.initials: S
authors.lastname: Mazzara
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Sinisi
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Cardaci
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy.
authors.forename: Riccardo Lorenzo
authors.initials: RL
authors.lastname: Rossi
authors.affiliation: Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Policlinico di Sant'Orsola, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Muratori
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy; DISSCO, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Bombaci
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000097:blood* / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D019693:Hepatitis, Autoimmune / Q000097:blood* / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D040081:Protein Array Analysis / Q000379:methods*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D016326:Extracellular Matrix Proteins; C088980:chondroadherin