A Molecular Approach to Chronic Rejection: Antibody or T-Cell Mediated?
Montefiore Medical Center Transplant Center, Albert Einstein College of Medicine, NY
Meeting: 2017 American Transplant Congress
Abstract number: 398
Keywords: Rejection
Session Information
Session Name: Concurrent Session: Diagnosis of Antibody Mediated Rejection in Kidney Transplant Recipients
Session Type: Concurrent Session
Date: Tuesday, May 2, 2017
Session Time: 2:30pm-4:00pm
Presentation Time: 2:42pm-2:54pm
Location: E354a
Despite the advances in diagnosis of chronic antibody-mediated rejection (CAMR), chronic T cell mediated rejection (CTCMR) is solely defined by Banff classification as chronic allograft arteriopathy. We hypothesize that T cell immunity might play a role in 2 conditions: donor-specific antibody (DSA) negative transplant glomerulopathy (TGP) and interstitial fibrosis and tubular atrophy (IFTA) with inflammation (i> 0).
Methods: A total of 101 for-cause renal allograft biopsies were studied using Affymetrix HuGene 1.0 ST expression arrays in the following groups; G1(n=16):normal, G2(n=33):CAMR, G3(n=27) CTCMR, G3A (n=17): IFTA with i > 0, G3B (n=10): TGP without DSA, G4 (n=12): IFTA without DSA and inflammation (i=0), and G5(n=13):DSA+ IFTA with i>0 but no C4d or microvascular inflammation.
Results: CAMR biopsies (G2) showed significantly increased expression of DSA associated (DSAST) and gamma-interferon and rejection associated (GRIT) transcripts when compared to G1, G3 and G5. However, CTCMR biopsies, whether G3A or G3B, had increased expression of cytotoxic T (CAT), regulatory T (TREG) and B cell (BAT) associated transcripts when compared to G1 or G4 but not DSAST (Table 2). G5 biopsies did not show increased expression of DSAST but CAT, TREG, and BAT. There was no significantly increased expression of any pathogenesis based transcripts in G4 biopsies.
Conclusion: In summary, we conclude that: 1: Increased DSAST transcripts is a specific biomarker for molecular diagnosis of AMR; 2: DSA negative TGP and IFTA with inflammation biopsies have a unique molecular signature with increased expression of CAT, TREG, and BAT but not DSAST suggesting that it could be classified as chronic TCMR; 3: DSA+ biopsies with IFTA with i>0 but no C4d or MVI did not show increased expression of DSAST but CAT, TREG, and BAT, similar to CTCMR biopsies.
| Pathogenesis Based Transcripts | G2 VS G1 | G3A VS G1 | G3B VS G1 | G3 VS G4 | G5 VS G1 |
| GRIT | 0.017 | 0.08 | 0.04 | 0.007 | 0.05 |
| CAT | 0.004 | 0.04 | 0.01 | 0.005 | 0.01 |
| TREG | 0.013 | 0.03 | 0.01 | 0.004 | 0.01 |
| BAT | 0.09 | 0.05 | 0.02 | 0.005 | 0.03 |
| NKAT | 0.09 | 0.17 | 0.13 | 0.03 | 0.07 |
| CMAT | 0.02 | 0.09 | 0.03 | 0.01 | 0.03 |
| DSAST | 0.007 | 0.35 | 0.27 | 0.24 | 0.09 |
| ENDAT | 0.32 | 0.57 | 0.34 | 0.16 | 0.15 |
CITATION INFORMATION: Kamal L, O Broin P, Lubetzky M, Bao Y, Akalin E. A Molecular Approach to Chronic Rejection: Antibody or T-Cell Mediated? Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Kamal L, Broin PO, Lubetzky M, Bao Y, Akalin E. A Molecular Approach to Chronic Rejection: Antibody or T-Cell Mediated? [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/a-molecular-approach-to-chronic-rejection-antibody-or-t-cell-mediated/. Accessed November 22, 2024.« Back to 2017 American Transplant Congress