Timing and Donor-Specific Antibodies, but Not C4d Deposition, Determine Leukocyte Infiltration in Renal Allograft Biopsies with the Histological Picture of Antibody-Mediated Rejection

J. Callemeyn¹, A. Senev¹, E. Lerut², M. Coemans¹, D. Kuypers¹, W. Gwinner³, M. Essig⁴, D. Anglicheau⁵, P. Marquet⁶, M. Naesens¹

¹Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium, ²Department of Pathology, University Hospitals Leuven, Leuven, Belgium, ³Department of Nephrology, Hannover Medical School, Hannover, Germany, ⁴Department of Nephrology, Dialysis and Transplantation, University of Limoges, Limoges, France, ⁵Necker-Enfants Malades Institute, French National Institute of Health and Medical Research U1151, Paris, France, ⁶U850 INSERM, University of Limoges, Limoges, France

Meeting: 2019 American Transplant Congress

Abstract number: A20

Keywords: Biopsy, Gene expression, Kidney transplantation, Leukocytes

Session Information

Session Name: Poster Session A: Acute Rejection

Session Type: Poster Session

Date: Saturday, June 1, 2019

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Hall C & D

*Purpose: Diagnosis of antibody-mediated rejection following kidney transplantation can be challenging, given the limited specificity of individual histological parameters and time-dependent occurrence of histological confounders. Moreover, despite substantial improvement in detection of donor-specific antibodies (DSA), often no HLA-DSA can be demonstrated in patients with the histological picture of ABMR. It is unclear whether this DSA-negative phenotype reflects a distinct clinicopathological entity with different effector mechanisms.

*Methods: Microarray analysis was performed of renal allograft biopsies fulfilling the histological Banff 2017 criteria for ABMR (ABMRh). Concurrent TCMR, borderline changes, BKV nephropathy and glomerulonephritis were used as exclusion criteria. Utilizing the CIBERSORT algorithm, deconvolution analysis of probeset signals was performed to estimate the relative and absolute leukocyte subtypes within the renal allograft.

*Results: In a cohort of 224 kidney transplant biopsies that were assessed using whole-genome transcriptomics, a total of 32 biopsies fulfilled the histological Banff 2017 criteria for ABMR (ABMRh), of which 14/32 (43,8%) did not have detectable HLA-DSA (DSAnegABMRh). Individual genes were upregulated similarly in both DSAposABMRh and DSAnegABMRh compared to normal biopsies. Among 22 leukocyte subtypes, only monocyte infiltration was significantly larger in DSAposABMRh compared to DSAnegABMRh. Utilizing peritubular C4d deposition as a proxy for DSA in DSAnegABMRh did not demonstrate monocyte infiltration difference. In addition, no other cellular infiltration differences between C4dposABMRh (n=13) and C4dnegABMRh (n=19) were found. ABMRh cases that occurred within the first three months after transplantation (n=11) had a significant increase of infiltrating macrophages and CD8+ T-cells compared to cases arising beyond one year (n=20).

*Conclusions: Timing and DSA status, but not C4d deposition, appear to influence cellular infiltration patterns in renal allograft biopsies with the histological picture of ABMR. Additional molecular studies are currently being performed to investigate the time-dependent cellular component of ABMR pathophysiology.

To cite this abstract in AMA style:

Callemeyn J, Senev A, Lerut E, Coemans M, Kuypers D, Gwinner W, Essig M, Anglicheau D, Marquet P, Naesens M. Timing and Donor-Specific Antibodies, but Not C4d Deposition, Determine Leukocyte Infiltration in Renal Allograft Biopsies with the Histological Picture of Antibody-Mediated Rejection [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/timing-and-donor-specific-antibodies-but-not-c4d-deposition-determine-leukocyte-infiltration-in-renal-allograft-biopsies-with-the-histological-picture-of-antibody-mediated-rejection/. Accessed May 18, 2025.

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