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Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity
Published on: June 7, 2017
The macrophage infiltration index and matrix metalloproteinase-II expression as a predictor of chronic allograft
Abstract:
The presence of macrophages on renal biopsy specimens is considered an important cofactor in the development of chronic allograft nephropathy (CAN). Macrophages can activate the expression of matrix metalloproteinases (MMP), which induce glomerulosclerosis, arteriosclerosis, and interstitial fibrosis. The aim of our study was to demonstrate if they were related to the development of CAN. We analyzed matrix metalloproteinase (MMP) expression with specific monoclonal antibodies on 53 kidney biopsies performed due to the suspicion of a first acute rejection (AR) episode: 24 of the grafts have been lost due to CAN and the rest are still functioning. The group with CAN showed worse graft function and greater proteinuria from the beginning. The macrophage infiltration index (MI) expression was significantly higher in that group also (18.8 +/- 12 vs 12.5 +/- 9.15; P < .05), with a more important presence of macrophages in the interstitium and tubules. We observed a positive correlation between MI and tubular infiltration (r(2) = 0.52; P < .001) and between MMP-II and MI in the interstitium (r(2) = 0.3; P < .05) and with the global MI (r(2) = 0.3; P < 0.05). The last correlation was more powerful in the group with CAN (r(2) = 0.4; P < .05). According to our experience, global MI and tubular infiltration during an AR episode are good markers of long-term graft survival. The correlation between MI and MMP-II supports the role of macrophages in the development of CAN, although further studies are needed to clarify the nature of this relationship.
Insights
Macrophages in kidney transplants are linked to chronic allograft nephropathy (CAN). Higher macrophage infiltration (MI) and tubular infiltration during acute rejection (AR) predict long-term graft survival and correlate with matrix metalloproteinase-II (MMP-II).
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Macrophages are implicated in chronic allograft nephropathy (CAN) development.
- Macrophages can activate matrix metalloproteinases (MMPs), contributing to kidney damage like glomerulosclerosis and fibrosis.
Purpose of the Study:
- To investigate the relationship between macrophage infiltration, MMP expression, and the development of CAN.
- To assess if macrophage infiltration and MMPs are predictive markers for long-term kidney allograft survival.
Main Methods:
- Analysis of 53 kidney biopsies from patients with suspected acute rejection (AR).
- Quantification of macrophage infiltration index (MI) and matrix metalloproteinase-II (MMP-II) expression using monoclonal antibodies.
- Correlation analysis between MI, tubular infiltration, MMP-II, and graft outcomes (CAN development, graft survival).
Main Results:
- Patients who developed CAN had significantly higher macrophage infiltration index (MI) compared to those with functioning grafts.
- Higher MI, particularly in the interstitium and tubules, correlated positively with tubular infiltration and MMP-II expression.
- The correlation between MI and MMP-II was stronger in the CAN group, suggesting a role in disease progression.
Conclusions:
- Global macrophage infiltration and tubular infiltration during AR episodes are significant indicators of long-term kidney allograft survival.
- The observed correlation between macrophage infiltration and MMP-II supports the role of macrophages in the pathogenesis of CAN.
- Further research is warranted to fully elucidate the intricate relationship between macrophages and MMPs in CAN development.
