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Updated: Aug 22, 2026
Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity
Published on: June 7, 2017
Glomerular monocyte/macrophage influx correlates strongly with complement activation in 1-week protocol kidney
S Sund1, A V Reisaeter, H Scott
1Department/Institute of Pathology, Rikshospitalet University Hospital, Oslo, Norway. Stale.sund@helse-forde.no
Insights
Monocytes/macrophages (MO) in kidney allografts correlate with complement activation and acute rejection. Early detection of high numbers of glomerular MO may indicate antibody-mediated acute rejection (AbAR) within one week post-transplant.
Area of Science:
- Nephrology
- Immunology
- Transplantation
Background:
- The role of monocytes/macrophages (MO) in kidney transplant rejection is not fully understood.
- Previous studies showed MO influx associated with complement activation and acute rejection (AR) in living-donor recipients.
- This study investigates the relationship between MO and complement activation in kidney biopsies.
Purpose of the Study:
- To analyze glomerular and interstitial monocytes/macrophages (MO) in kidney allograft biopsies.
- To determine the correlation between MO infiltration and complement activation.
- To identify potential diagnostic markers for acute antibody-mediated rejection (AbAR).
Main Methods:
- Twenty-seven protocol biopsies were stained for MO markers (calprotectin/L1, CD68).
- Glomerular and interstitial MO counts were performed.
- Results were compared with complement deposition data and clinical AR information.
Main Results:
- Higher intraglomerular MO numbers (L1 and CD68) were observed in cases with diffuse C4d deposition (AbAR).
- Specific cut-offs for L1 (10) and CD68 (6) MO per glomerulus showed high specificity for AbAR diagnosis.
- Interstitial MO numbers were higher in AR but did not differentiate complement-positive from negative AR.
Conclusions:
- A strong correlation exists between complement activation and early glomerular MO influx in kidney allografts, suggesting a causal link.
- Quantifying glomerular MO at one week post-transplant can indicate AbAR.
- Specific MO counts can serve as early diagnostic indicators for AbAR.
Background:
The specific role of monocytes/macrophages (MO) in kidney graft rejection is not yet fully elucidated. In a recent protocol biopsy study of living-donor recipients, we demonstrated massive capillary influx of MO, associated with severe complement activation and acute rejection (AR) 1 week after transplantation [Sund et al.]. To gain further insight into the possible relationship between MO and complement activation, we analyzed glomerular and interstitial MO in these biopsies.
Methods:
Twenty-seven protocol biopsies were stained with antibodies to calprotectin (L1) and CD68 as markers for MO. Cells were counted as an average number per glomerulus and as an average number per defined visual field in the interstitium. Polymorphonuclear leukocytes (PMN) were counted in glomeruli and interstitium by light microscopy. Baseline specimens from 10 of the patients served as controls. The results were compared with data on deposition of complement from the foregoing study, and with histopathologic and clinical data on AR.
Results:
Cases with diffuse C4d deposition in peritubular capillaries consistent with acute antibody-mediated rejection (AbAR) (n = 4) had significantly higher numbers of intraglomerular MO than the other protocol biopsies (L1: median 20.7 vs 3.6, p = 0.0002; CD68: median 10.1 vs. 2.0, p = 0.0008). With a cut-off of 10 L1-positive and 6 CD68-positive MO, the specificity for the diagnosis of AbAR was 96% and 91%, respectively. The number of interstitial MO was significantly higher in patients with AR than in those without, but in contrast to glomerular MO, interstitial MO could not discriminate between complement positive and negative AR. The number of glomerular and interstitial PMNs was significantly higher in the AbAR group than in the other protocol biopsies.
Conclusions:
The strong correlation between complement activation and early glomerular influx of MO in the kidney allograft suggests a causal relationship between these 2 events. At 1 week after transplantation, a number of 10 L1-positive and 6 CD68-positive MO per glomerulus indicates AbAR.
