Apolipoprotein A1 and C-terminal fragment of α-1 antichymotrypsin are candidate plasma biomarkers associated with acute renal allograft rejection

Mary E. Ziegler, Tingchao Chen, James F. Leblanc, Xuelian Wei, David W. Gjertson, Ker Chau Li, Mazdak Khalighi, Charles R. Lassman, Jeffrey L. Veale, H. Albin Gritsch, Elaine F. Reed

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)388-395
Number of pages8
JournalTransplantation
Volume92
Issue number4
DOIs
StatePublished - Aug 27 2011
Externally publishedYes

Fingerprint

Apolipoproteins C
Apolipoprotein A-I
Allografts
Biomarkers
Kidney
Peptides
Biopsy
Proteins
Enzyme-Linked Immunosorbent Assay
Needle Biopsy
Blood Proteins
Mass Spectrometry
Lasers
Morbidity
Sensitivity and Specificity
Antibodies

Keywords

  • Acute cellular rejection
  • Biomarker
  • Proteomics
  • Renal
  • Transplantation

ASJC Scopus subject areas

  • Transplantation

Cite this

Apolipoprotein A1 and C-terminal fragment of α-1 antichymotrypsin are candidate plasma biomarkers associated with acute renal allograft rejection. / Ziegler, Mary E.; Chen, Tingchao; Leblanc, James F.; Wei, Xuelian; Gjertson, David W.; Li, Ker Chau; Khalighi, Mazdak; Lassman, Charles R.; Veale, Jeffrey L.; Gritsch, H. Albin; Reed, Elaine F.

In: Transplantation, Vol. 92, No. 4, 27.08.2011, p. 388-395.

Research output: Contribution to journalArticle

Ziegler, ME, Chen, T, Leblanc, JF, Wei, X, Gjertson, DW, Li, KC, Khalighi, M, Lassman, CR, Veale, JL, Gritsch, HA & Reed, EF 2011, 'Apolipoprotein A1 and C-terminal fragment of α-1 antichymotrypsin are candidate plasma biomarkers associated with acute renal allograft rejection', Transplantation, vol. 92, no. 4, pp. 388-395. https://doi.org/10.1097/TP.0b013e318225db6a
Ziegler, Mary E. ; Chen, Tingchao ; Leblanc, James F. ; Wei, Xuelian ; Gjertson, David W. ; Li, Ker Chau ; Khalighi, Mazdak ; Lassman, Charles R. ; Veale, Jeffrey L. ; Gritsch, H. Albin ; Reed, Elaine F. / Apolipoprotein A1 and C-terminal fragment of α-1 antichymotrypsin are candidate plasma biomarkers associated with acute renal allograft rejection. In: Transplantation. 2011 ; Vol. 92, No. 4. pp. 388-395.
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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.",
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T1 - Apolipoprotein A1 and C-terminal fragment of α-1 antichymotrypsin are candidate plasma biomarkers associated with acute renal allograft rejection

AU - Ziegler, Mary E.

AU - Chen, Tingchao

AU - Leblanc, James F.

AU - Wei, Xuelian

AU - Gjertson, David W.

AU - Li, Ker Chau

AU - Khalighi, Mazdak

AU - Lassman, Charles R.

AU - Veale, Jeffrey L.

AU - Gritsch, H. Albin

AU - Reed, Elaine F.

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N2 - 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.

AB - 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.

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KW - Biomarker

KW - Proteomics

KW - Renal

KW - Transplantation

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