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C4d deposition is associated with immune cells infiltrating in kidney allograft glomerulitis and peritubular
Juan Jin1, Yi Wen Li, Qiang He
1a Department of Nephrology , Zhejiang Provincial People's Hospital , Hangzhou , P.R. China.
Insights
Immune cell composition in kidney biopsies differs based on C4d deposition. Macrophages dominate in C4d-positive cases, while T cells are more prevalent in C4d-negative cases, indicating distinct immune responses.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- C4d deposition is a marker of antibody-mediated rejection in kidney allografts.
- The role of specific immune cell subsets in relation to C4d deposition is not fully understood.
Purpose of the Study:
- To quantify and characterize immune cells within glomeruli and peritubular capillaries (PTCs).
- To investigate the relationship between immune cell infiltration and C4d deposition in kidney biopsies.
Main Methods:
- Immunohistochemistry was used to detect C4d, CD3 (T cells), CD68 (macrophages), granzyme B, and Foxp3 (regulatory T cells).
- Immune cells within glomeruli and PTCs were enumerated in C4d-positive and C4d-negative biopsy specimens.
Main Results:
- C4d deposition was observed in 26 of 51 biopsy specimens.
- Total infiltrating immune cells were significantly higher in C4d-positive compared to C4d-negative biopsies.
- Macrophages were predominant in C4d-positive biopsies, while T cells were more numerous in C4d-negative biopsies.
- Diffuse C4d deposition showed a trend towards higher macrophage and lower T cell infiltration compared to focal deposition, though not statistically significant.
- Glomerular and PTC T cells exhibited a cytotoxic phenotype (granzyme B positive).
Conclusions:
- PTC C4d deposition is associated with the total number of infiltrating immune cells in kidney biopsies.
- The immune cell infiltrate composition differs based on C4d status, with macrophages dominating in C4d-positive and T cells in C4d-negative kidneys.
- Kidney T cells, both glomerular and PTC, possess a cytotoxic phenotype.
Objective:
The aim of our study was to determine the amount and composition of immune cells within glomeruli and PTCs and its relationship with C4d deposition.
Materials And Methods:
Immunohistochemistry staining for C4d, CD3, CD68, granzyme B and Foxp3 was used for phenotyping and enumerating immune cells within intracapillaries.
Results:
C4d staining was present in 26 biopsy specimens (C4d(+)) and negative in 25 specimens (C4d(-)). The total number of infiltrating cells in glomerulus and PTC in C4d(+) was significantly higher than in C4d(-). Although the C4d(+) showed a significantly higher mean number of macrophages per glomerulus and PTC than in C4d(-) group, the C4d(-) showed a higher mean number of T cells per glomerulus and PTC than in C4d(+). Comparing cell counts in diffuse C4d(+) and focal C4d(+) groups, a significant difference of absolute numbers of intracapillary cells could be observed in glomeruli and PTCs. The mean number of macrophages per glomerulus and PTC in diffuse C4d(+) was greater than that of the focal C4d(+), while mean T cells per glomerulus and PTC were less in cases of diffuse C4d(+) than in focal C4d(+). The differences, however, did not achieve statistical significance. Not only glomerular T cells but also PTCs are granzyme B positive T cells totally.
Conclusion:
The total number of infiltrating cells in glomeruli and PTC has association with PTC C4d deposition; the infiltrating cells were predominantly macrophages in C4d(+), especially in diffuse C4d(+), whereas the infiltrating cells were predominantly T cells in C4d(-). Glomerular and PTC T cells were cytotoxic phenotype completely.
