Microvascular Inflammation in Kidney Transplant Biopsies in the Absence of HLA-DSA Displays Intense Cytotoxic T-cell and NK Cell but Not Plasma Cell Infiltration

A. Buxeda¹, L. Llinàs-Mallol¹, J. Gimeno², D. Redondo-Pachón¹, C. Arias-Cabrales¹, C. Burballa¹, A. Puche², M. Pérez-Sáez¹, J. Pascual³, M. Crespo¹

¹Nephrology Department, Hospital del Mar, Institute Mar for Medical Research (IMIM), Barcelona, Spain, ²Pathology Department, Hospital del Mar, Institute Mar for Medical Research (IMIM), Barcelona, Spain, ³Nephrology Department, Hospital Universitario 12 de Octubre. Institute Mar for Medical Research (IMIM), Madrid, Spain

Meeting: 2022 American Transplant Congress

Abstract number: 573

Keywords: Biopsy, Natural killer cells, Rejection, T cell graft infiltration

Topic: Basic Science » Basic Clinical Science » 19 - Chronic Organ Rejection

Session Information

Session Name: Chronic Organ Rejection

Session Type: Rapid Fire Oral Abstract

Date: Tuesday, June 7, 2022

Session Time: 5:30pm-7:00pm

Presentation Time: 5:50pm-6:00pm

Location: Hynes Room 309

*Purpose: Microvascular inflammation (MVI) without evidence of HLA-donor-specific antibodies (HLA-DSA) or C4d⁺deposition remains an enigmatic phenotype, which cannot be classified as antibody-mediated rejection (ABMR) according to recent Banff classifications.

*Methods: We aimed to compare peripheral blood lymphocyte (PBL) distribution and infiltrating immune cells in kidney transplant (KT) biopsies presenting MVI (g+ptc≥2) without C4d⁺ and HLA-DSA, ABMR, and normal histology to explore the role of immune cells in these entities.

*Results: From 221 allograft biopsies with ABMR (n=73), MVI (n=32), and normal (n=116) diagnosis. MVI patients showed a decrease in the absolute number of T-cells compared with ABMR and normal cases (p=0.020 and p=0.006) due to a significant decrease of CD4⁺ T-cells compared to normal cases (p=0.013) and a reduction of CD8⁺ T-cells compared to ABMR (p=0.029). ABMR and MVI presented a lower absolute number of circulating Natural Killer (NK) cells than normal cases. Immunohistochemistry assessment was performed in 22 ABMR, 13 MVI, and 16 normal cases. Glomeruli in ABMR and MVI had more T-cells and CD68⁺infiltration than normal biopsies, although TIA1⁺ was only increased in MVI (p<0.001), suggesting heightened T-cell cytotoxic capacity. Peritubular capillaries displayed more circulating T-cells, CD56⁺, TIA1⁺, and CD68⁺ in ABMR and MVI groups. Contrarily, MVI cases showed mild circulating plasma cell infiltration (CD138⁺) in peritubular capillaries (p=0.059) and interstitial aggregates (p=0.024) compared to ABMR (Figure).

*Conclusions: In conclusion, MVI without HLA-DSA and C4d⁺ displays decreased circulating T-cell and NK cells, and intense T-cell and NK cell cytotoxic infiltration in the allograft, similar to ABMR. However, the deficiency of plasma cell infiltration in MVI suggests a different underlying stimulus than ABMR.

Figure. Immunohistochemical assessment in KT biopsies.

To cite this abstract in AMA style:

Buxeda A, Llinàs-Mallol L, Gimeno J, Redondo-Pachón D, Arias-Cabrales C, Burballa C, Puche A, Pérez-Sáez M, Pascual J, Crespo M. Microvascular Inflammation in Kidney Transplant Biopsies in the Absence of HLA-DSA Displays Intense Cytotoxic T-cell and NK Cell but Not Plasma Cell Infiltration [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/microvascular-inflammation-in-kidney-transplant-biopsies-in-the-absence-of-hla-dsa-displays-intense-cytotoxic-t-cell-and-nk-cell-but-not-plasma-cell-infiltration/. Accessed May 30, 2025.

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