Purpose: Rejection significantly worsens the graft function and survival. We studied monocyte-macrophage compartmental infiltration of 62 kidney transplant biopsies with diagnosis of: acute antibody mediated rejection (aABMR, n=9), chronic antibody mediated rejection (cABMR, n=13), acute cellular rejection type I (ACR I, n=11), acute cellular rejection type II (ACRII, n=13), and 15 protocol biopsies from kidney transplants with stable function as controls. Next we studied the relationship between these findings and allograft function and survival.

Methods: Immunohistochemical and fluorescent stainings were applied to study monocyte-macrophage infiltration. Infiltrating monocytes were characterized by double staining with CD14 and CD16. Infiltrating macrophages were identified as follows: CD68+CD80 (M1 type) and CD68+CD163 (M2 type). Histopathological data were correlated to eGFR and proteinuria at the time of biopsy, 3, 6 and 12 months post-rejection.

Results: The presence of CD68+macrophages in kidney biopsies was significantly associated with rejection compared to stable patients regardless of histopathological subtype (p=<0,01). The presence of CD68+CD163+ macrophages was signigicantly associated with a lower eGFR at all timepoints studied (p<0,001). Glomerular infiltration by classical and intermediate monocytes and and the presence of non-classical monocytes in the interstitium were significantly associated with rejection regardless of rejection subtype (p=<0,01). cABMR was characterized by glomerular and tubulointerstitial CD68+ macrophage infitration, and glomerular and tubulointerstitial classical and intermediate monocyte distribution as compared to aABMR (p=<0,05). ACRI and ACRII were charactherized by vascular and tubulointerstitial distribution of CD68+ cells as compared to aABMR (p=<0,05).

Conclusions: In sharp contrast to T cells, the presence of CD68+macrophages in a kidney transplant biopsy is significantly associated with rejection regardless of subtype. There are significant compartmental differences in the distribution of different macrophage and monocyte subtypes between aABMR and cABMR, as well as between ACR I/II and aABMR.

CITATION INFORMATION: van den Bosch T, Clahsen-van Groningen M, Rezaee F, Hesselink D, Nieboer D, Steyerberg E, Baan C, Rowshani A. Compartmental Infiltration of Kidney Allograft with Monocyte-Macrophage Subtypes Defines the Type of Rejection. Am J Transplant. 2017;17 (suppl 3).

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