Interpreting CD56+ and CD163+ Infiltrates in Early versus Late Renal Transplant Biopsies

Abstract

Background: CD56+ and CD163+ cell infiltration in human kidney transplant biopsies have not been fully evaluated. Methods: We investigated the association of CD56+ and CD163+ cell infiltration with human kidney transplant biopsies with antibody- or T-cell-mediated rejection (TCMR) and other histologic lesions. One hundred and seventy four clinically indicated transplant biopsies were included in this analysis. Immunohistochemical staining for C4d, CD56 and CD163 was performed. Results: One hundred and seventy four indication biopsies were divided into early (≤1 year posttransplant; n = 49) and late (>1 year posttransplant; n = 125) biopsies. High numbers of CD56+ cells were uncommon in early biopsies except for those with antibody-mediated rejection (AMR) only. On the other hand, high numbers of CD56+ cells were observed in late biopsies diagnosed as TCMR only, AMR only, and TCMR combined with AMR. In early biopsies, both CD56+ and CD163+ infiltrates correlated strongly with interstitial inflammation, tubulitis, and peritubular capillaritis (ptc) scores. The ci and ct scores, however, were correlated only with the number of CD56+ cells. In late biopsies, on the other hand, the number of CD56+ infiltrates was correlated only with ptc, while the number of CD163+ infiltrates was weakly correlated with any histologic lesion. Multivariable analyses showed that chronic active AMR and the number of CD56+ cells/10 HPF were independently associated with death-censored graft failure post-biopsy. The number of CD163+ cells was not correlated with any pathologic lesion and post-biopsy graft failure. CD56+ infiltrates were also associated with interstitial fibrosis and tubular atrophy. Conclusions: Intragraft CD56+ cell infiltrates were significantly associated with AMR and subsequent poor clinical outcomes.

Interferon-γ production by tubulointerstitial human CD56bright natural killer cells contributes to renal fibrosis and chronic kidney disease progression

“…16 Intragraft NK cells (CD56 þ cells) in kidney transplant biopsy specimens have also been reported to be associated with interstitial fibrosis and poor clinical outcomes. 17,18 However, single staining for these antigens is not sufficiently specific to directly identify NK cells, given the broader expression of these markers in T-cell subpopulations. 19,20 Furthermore, expression of both CD57 and CD16 antigens within the NK cell compartment is primarily restricted to CD56 dim NK cells, highlighting an underrepresentation of markers identifying CD56 bright NK cells in these previous studies.…”

Expression patterns of CD56+ and CD16+ cells in renal transplant biopsies with acute rejection: Associations with microcirculation injuries and graft survival

“…That can suggest a role of NK cells in the mechanism of microcirculation injury in acute rejections, more specifically in glomerular compartment. Hidalgo et al also studied biopsies from renal transplant by CD56 immunostaining and they observed higher number of CD56+ cells associated with peritubular capillaritis and Shin et al observed an increased number of CD56 + cells correlated with late biopsies, chronic active antibody‐mediated rejection and graft survival. None of those studies found associations between CD56+ infiltrate and glomerulitis.…”

The Role of Natural Killer Cells in the Immune Response in Kidney Transplantation

“…These data support the different role of NK cells in ABMR compared to the TCMR. Shin et al also reported a positive correlation between the number of CD56 + cells and the severity of T cell-mediated rejection (63). In addition, it has been recently demonstrated that transcripts from activated NK cells are the only among those from leukocyte types that differentiate antibody-and T cell-mediated rejections and correlate with transplant outcome (55).…”