title: Apolipoprotein A1 and C-terminal fragment of α-1 antichymotrypsin are candidate plasma biomarkers associated with acute renal allograft rejection.
abstract: BACKGROUND
  Current diagnostic methods of renal allograft rejection are neither sensitive nor specific. Needle biopsies are invasive and associated with patient morbidity. Thus, it is desirable to develop noninvasive tests to predict and diagnose rejection.
  
  
  METHODS
  Using a case-control approach, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry was used to identify plasma proteins associated with renal allograft rejection. From each rejection patient (n=16), two plasma samples (one near the biopsy date and the other at a time postbiopsy) were compared. Biopsy-confirmed nonrejection patients (n=48) were further analyzed as controls. Antibody-based quantitative enzyme-linked immunosorbent assay was performed to validate candidate biomarker apolipoprotein A1 (Apo A1) in a subset of the original and a second cohort of biopsy-confirmed rejection (n=40) and nonrejection (n=70) patients.
  
  
  RESULTS
  Twenty-two proteins/peptides showed significant differences between rejection and postrejection samples. Peptides 5191 Da and 4467 Da detected rejection with 100% sensitivity and 94% specificity. The 4467 Da peptide was identified as the C-terminal fragment of α-1 antichymotrypsin and a 28 kDa protein was determined as Apo A1. Both protein levels were significantly lower at rejection compared with postrejection. Protein levels of nonrejection patients were similar to the postrejection samples. Apo A1 enzyme-linked immunosorbent assay results showed significantly lower Apo A1 levels (P=0.001 for the original and P=4.14E-11 for the second cohort) at the time of rejection compared with nonrejection which coincides with the SELDI findings.
  
  
  CONCLUSIONS
  Together α-1 antichymotrypsin, Apo A1, and the unidentified 5191 Da peptide provide a plasma molecular profile, and this is associated with acute cellular renal allograft rejection.
authors: Department of Pathology and Laboratory Medicine, UCLA School of Public Health, Los Angeles, CA 90095, USA.
authors: Mary E
authors: ME
authors: Ziegler
authors: Tingchao
authors: T
authors: Chen
authors: James F
authors: JF
authors: LeBlanc
authors: Xuelian
authors: X
authors: Wei
authors: David W
authors: DW
authors: Gjertson
authors: Ker-Chau
authors: KC
authors: Li
authors: Mazdak A
authors: MA
authors: Khalighi
authors: Charles R
authors: CR
authors: Lassman
authors: Jeffrey L
authors: JL
authors: Veale
authors: H Albin
authors: HA
authors: Gritsch
authors: Elaine F
authors: EF
authors: Reed
mesh_terms: D000208:Acute Disease; D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000706:statistics & numerical data; D005260:Female; D006084:Graft Rejection / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D040081:Protein Array Analysis; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000514:alpha 1-Antichymotrypsin / Q000097:blood*
chemical_list: D016632:Apolipoprotein A-I; D015415:Biomarkers; D010446:Peptide Fragments; D000514:alpha 1-Antichymotrypsin