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Published on: May 7, 2019
Pathological study on the relationship between C4d, CD59 and C5b-9 in acute renal allograft rejection
1Blood Purification Center, Niigata University Hospital, Niigata City, Japan. snishi@med.niigata-u.ac.jp
Insights
In renal allografts with acute rejection, CD59 on peritubular capillaries (PTC) was present, but C5b-9 was not, suggesting complement regulation despite C4d deposition. C5b-9 on tubular basement membranes indicates independent injury.
Area of Science:
- Nephrology
- Immunology
- Transplantation
Background:
- Acute rejection of renal allografts can involve complement activation.
- C4d deposition on peritubular capillaries (PTC) is a marker of antibody-mediated rejection.
- The role of terminal complement complex (C5b-9) and its regulators (CD59) in renal allograft rejection needs further clarification.
Purpose of the Study:
- To investigate the expression of CD59 and C5b-9 on PTC in renal allografts with acute rejection and C4d deposition.
- To evaluate the relationship between C4d, CD59, and C5b-9 in the context of acute rejection.
Main Methods:
- Analysis of renal biopsies from patients with acute rejection and normal donors.
- Immunohistochemical staining for C4d, CD59, and C5b-9 on PTC and tubular basement membranes (TBM).
Main Results:
- C4d deposition was observed in 30% of acute rejection cases.
- CD59 was expressed on PTC in all acute rejection cases.
- C5b-9 was not found on PTC but was deposited on TBM in 50% of acute rejection cases, including those with C4d deposition.
- Normal donors showed intensive CD59 on PTC and weak C5b-9 on TBM.
Conclusions:
- A dissociation exists between C4d and C5b-9 deposition on PTC in acute renal allograft rejection.
- High CD59 expression on PTC may contribute to this dissociation.
- Intensive C5b-9 deposition on TBM suggests an independent immunological injury targeting tubular cells.
Abstract:
In order to evaluate the activation or inhibition of the later phases of classical complement cascade in renal allograft presenting with acute rejection, particularly with C4d deposition on the peritubular capillary (PTC), we observed the expression of CD59 and C5b-9 on the PTC. Subjective cases were divided into two groups, an acute rejection group, of 4 males and 6 females, and a normal donor group, of 5 males and 5 females. Renal biopsies were performed at the onset of acute rejection and at the transplant operation, before reperfusion. C4d deposition on PTC was found in three of 10 cases (30%) with biopsy proven acute rejection, whereas CD59 on PTC was positively expressed in all of the rejection cases. Although C5b-9 was not observed on PTC in the acute rejection group, it was intensively deposited on the tubular basement membrane (TBM) in five cases, including the three with positive C4d on PTC. In the normal donor group, CD59 on PTC was intensively observed, whereas C5b-9 was weakly expressed on TBM. CD59, a complement regulatory factor, works as an inhibitory factor against the formation of C5b-9, a membrane attack complex. From our data, we noted the dissociation between the depositions of C4d and C5b-9 on PTC. The substantially expressed CD59 on PTC may affect this dissociation between C4d and C5b-9 on PTC. The intensive deposition of C5b-9 on TBM in acute rejection cases may suggest an independent immunological injury attacking tubular cells.
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