Increased Gene Transcripts Related to Immune Activation in Allografts but Not in Peripheral Blood of Patients with Donor-Specific Anti-HLA Antibodies Despite Lack of Histopathologic Findings of Rejection
Montefiore/Einstein Transplant Center, Bronx, NY
Meeting: 2013 American Transplant Congress
Abstract number: 30
Background: Donor specific antibodies (DSA) increase the risk of developing antibody-mediated rejection (AMR). However, some patients with DSA have normal biopsies, questioning the role of accommodation/ignorance. We investigated the mechanisms involved in protecting the allograft from AMR.
Methods: DSA were measured by Luminex single antigen beads. The biopsy and whole blood gene expression profiles were studied by Affymetrix HuGene 1.0 ST expression arrays.
Results: Gene expression analysis of 20 biopsies without DSA and normal histology (G1), 13 DSA+ with normal histology or non-specific mild fibrosis (G2) to 28 biopsies with DSA and acute or chronic AMR (G3) revealed differential gene expression profiles. Gene ontology revealed significant up-regulation of genes implicated in all aspects of immune response; including T&B cell, natural killer cell, and interferon-gamma activation in G3 compared to G1, while interferon-gamma and cytokine activation was observed in G2. Pathogenesis Based Transcript analysis (PBT) showed that in both G3 and G2, Interferon-Gamma and Rejection Induced (GRIT), Cytotoxic T-cell (CAT), Quantitative Constitutive Macrophage (CMAT), B-cell (BAT), Natural Killer Cell (NKAT), Endothelial Cell (ENDAT) associated transcripts and Donor Specific Antibody Selective Transcripts seen in AMR (DSAST) were significantly upregulated compared to G1 (Table). The GRIT, CAT, DSAST transcript levels were significantly higher in G3 compared to G2.
Gene expression analysis of blood samples (G1=12, G2=14, G3=28) revealed that while there was no significant difference in any PBT comparing G2 and G1, G3 revealed increased GRIT, CAT and CMAT expression compared to G1.
Conclusion: While DSA+ patients with AMR showed increased gene transcripts related to immune activity in their both kidney and blood samples, interestingly, DSA+ patients without histopathologic findings of rejection showed increased immune activity in their allografts but not in their blood indicating an ongoing local alloimune response but not accommodation or ignorance.
| Groups | GRIT | CAT | BAT | CMAT | NKAT | ENDAT | DSAST |
| Biopsy | |||||||
| G2 to G1 | 0.05 | 0.03 | 0.05 | 0.03 | 0.02 | 0.04 | 0.02 |
| G3 to G1 | 0.004 | 0.001 | 0.03 | 0.02 | 0.03 | 0.03 | 0.003 |
| G3 to G2 | 0.01 | 0.004 | 0.31 | 0.16 | 0.22 | 0.22 | 0.001 |
| Blood | |||||||
| G2 to G1 | 0.22 | 0.17 | 0.11 | 0.17 | 0.48 | 0.45 | 0.91 |
| G3 to G1 | 0.05 | 0.007 | 0.38 | 0.03 | 0.23 | 0.45 | 0.52 |
| G3 to G2 | 0.06 | 0.009 | 0.87 | 0.21 | 0.11 | 0.54 | 0.046 |
To cite this abstract in AMA style:
Hayde N, Bao Y, Pullman J, Boccardo GDe, Lubetzky M, Akalin E. Increased Gene Transcripts Related to Immune Activation in Allografts but Not in Peripheral Blood of Patients with Donor-Specific Anti-HLA Antibodies Despite Lack of Histopathologic Findings of Rejection [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/increased-gene-transcripts-related-to-immune-activation-in-allografts-but-not-in-peripheral-blood-of-patients-with-donor-specific-anti-hla-antibodies-despite-lack-of-histopathologic-findings-of-reject/. Accessed November 22, 2024.« Back to 2013 American Transplant Congress