Early infiltration of renal allografts with 27E10-positive macrophages and graft outcome

Abstract

Recently, we have demonstrated that acute cellular rejection is correlated with a massive infiltration of 27E10-positive macrophages. To examine the distribution of macrophage differentiation markers in the infiltrate in the very early post-transplantation period, two biopsies were taken intraoperatively, approximately 1 h following reperfusion, in each of 16 renal transplant recipients. One biopsy was taken for conventional histology and the other biopsy was snap-frozen. The sections were stained using an ABC indirect immunoperoxidase technique. A panel of monoclonal antibodies against three macrophage differentiation markers (27E10, 25F9 and RM3/1) was used to stain the sections. Using the early inflammation macrophage marker 27E10, there was an unexpected strong staining in 3 out of 16 biopsies. This severe infiltration of 27E10-positive macrophages with 10-20 macrophages per high power field (compared to 0-2 in others) was correlated in all cases with a poor outcome of the graft. All seven kidneys with no 27E10-positive infiltration showed a good function 6 weeks post-transplantation. The other macrophage markers, 25F9 and RM3/1, showed a less marked correlation with graft outcome. In conclusion, a massive infiltration of renal allografts with 27E10-positive macrophages 1 h post-transplantation may be a very early predictor of poor graft outcome.

An Increase in Myeloid-Related Protein Serum Levels Precedes Acute Renal Allograft Rejection

“…The finding of very early activation of MRP8/14-positive macrophages in this study is consistent with our previous observations with 1-h renal transplant biopsies, which indicated very early involvement of activated MRP8/14-positive macrophages and granulocytes in the immune response to the allograft (35). MRP8/14-positive macrophages and neutrophils are also the first cells to arrive at the inflammatory site in many animal models (12).…”

Glomerular monocytes predict worse outcomes after acute renal allograft rejection independent of C4d status

“…Several previous studies have shown an association between extent of CI MO infiltration and poor graft survival [16,[19][20][21]37]. Differences in patient population, immunosuppression, and treatment of acute rejection may account for this discrepancy.…”

“…Previous studies have demonstrated that glomerular and interstitial monocyte/macrophage (MO) infiltration in acute rejection have a detrimental effect on graft survival [16][17][18][19][20][21][22][23][24][25][26], and are associated with diffuse PTC C4d deposition in acute rejection [27]. In view of the correlation of PTC C4d deposition with reduced graft survival [6,[9][10][11][12], it is uncertain whether MO infiltration is a significant independent predictor of poor allograft outcome.…”

Macrophages in renal transplantation: Roles and therapeutic implications

“…Macrophage accumulation can be found early after transplantation [55] and its persistence in the allograft portends a poor prognosis [56]. Girlanda et al demonstrated that both monocytes and T cell infiltrates are present in rejecting allografts, but allograft dysfunction was only quantitatively associated with monocyte infiltration [57].…”