Increased Cytotoxic and Regulatory T Cell and B Cell Associated Gene Transcripts in Transplant Kidney Biopsies With Non-Specific IFTA and Interstitial Inflammation
Renal Division and Kidney Transplant Center, Computational Genomics Facility, Albert Einstein College of Medicine, Bronx, NY.
Meeting: 2015 American Transplant Congress
Abstract number: 376
Keywords: Gene expression
Session Information
Session Name: Concurrent Session: Kidney: Antibodies and Allograft Injury
Session Type: Concurrent Session
Date: Tuesday, May 5, 2015
Session Time: 2:15pm-3:45pm
Presentation Time: 3:27pm-3:39pm
Location: Room 118-AB
Background: Patients with non –specific interstitial fibrosis/tubular atrophy (IFTA) have lower graft survival if their biopsies have interstitial inflammation, described as “ i” in Banff classification, compared to patients without inflammation. We aimed to investigate the nature of the infiltrating cells using microarrays.
Methods: We identified 33 biopsies with non –specific IFTA for gene expression profiling comparing to 15 normal transplant kidney biopsies (Group 1). Biopsies with a diagnosis of acute rejection, recurrent or de novo glomerular disease, or polyoma nephropathy were excluded. Among the 33 biopsies with IFTA, 14 patients (Group 2) had no interstitial inflammation (i=0) and 19 patients (Group 3) had i>0. Gene expression profiles were analyzed by Affymetrix HuGene 1.0 ST expression arrays.
Results: There was no difference between the groups in terms of any demographic variables, including age, race, sex, panel reactive antibody levels, type of transplantation, immunosuppressive treatment, previous history of transplantation and acute rejection, serum creatinine levels, and donor characteristics. There was no difference in acute (t, v, g, and ptc) and chronic Banff injury scores (cg, ct, and mm) except for higher ci score (1.94±0.62 vs. 1.4±0.75, p < 0.05) and higher cv score (0.89±0.45 vs. 0.57±0.5, p<0.05) in group 3 compared to Group 2. There was no significant difference in expression of gene transcripts studied between the Groups 1 and 2 (Table). Increased intragraft gene transcripts associated with Cytotoxic T cells (CAT), Regulatory T (TREG) and B cells (BAT) were observed in Group 3 biopsies when compared to Group 1 and 2 biopsies. Constitutive macrophage associated gene transcripts (CMAT) were upregulated in Group 3 compared to Group 2. There was no difference in natural killer cell associated transcripts (NKAT) between the groups.
Conclusion: The biopsies of the patients with non –specific IFTA and interstitial inflammation showed increased expression of gene transcripts associated with cytotoxic and regulatory T and B cells reflecting an increased intra-graft alloimmune activity. Our results suggest that those biopsies could be classified as “chronic cellular rejection”.
| Pathogenesis based transcripts | G2 vs. G1 | G3 vs. G1 | G3 vs. G2 |
| CAT | 0.43 | 0.014 | 0.02 |
| TREG | 0.38 | 0.049 | 0.02 |
| BAT | 0.39 | 0.044 | 0.004 |
| NKAT | 0.69 | 0.35 | 0.09 |
| CMAT | 0.60 | 0.077 | 0.01 |
To cite this abstract in AMA style:
Akten S, Ajaimy M, Broin PO, Bao Y, Golden A, Akalin E. Increased Cytotoxic and Regulatory T Cell and B Cell Associated Gene Transcripts in Transplant Kidney Biopsies With Non-Specific IFTA and Interstitial Inflammation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/increased-cytotoxic-and-regulatory-t-cell-and-b-cell-associated-gene-transcripts-in-transplant-kidney-biopsies-with-non-specific-ifta-and-interstitial-inflammation/. Accessed November 21, 2024.« Back to 2015 American Transplant Congress