FC 109: 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

Abstract BACKGROUND AND AIMS 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. 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. METHODS A total of 221 allograft biopsies with ABMR (n = 73), MVI (n = 32) and normal (n = 116) diagnoses were analysed. RESULTS 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 with 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 increased 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 with ABMR (Figure 1). CONCLUSION 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 from ABMR.