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Complement activation during an active cytomegalovirus infection after renal transplantation: due to circulating
W J van Son1, W van der Bij, A M Tegzess
1Renal Transplantation Unit, University Hospital, Groningen, The Netherlands.
Insights
Cytomegalovirus (CMV) infection in renal transplant patients activates complement, increasing C3d and C3a des arg levels. This suggests the alternative complement pathway is involved, independent of immune complexes.
Area of Science:
- Immunology
- Nephrology
- Virology
Background:
- Complement system activation is crucial in immune responses and transplant outcomes.
- Cytomegalovirus (CMV) infections are common and serious complications in renal transplant recipients.
- Understanding complement system involvement in CMV infection is vital for managing transplant patients.
Purpose of the Study:
- To investigate complement system activation during active CMV infection in renal transplant patients.
- To assess the role of circulating immune complexes in this activation process.
- To explore the potential involvement of the alternative complement pathway.
Main Methods:
- Serial measurements of C3d, C3a des arg, and AP50 (alternative pathway) in renal transplant patients.
- Detection of circulating immune complexes using C1q binding assay, PEG precipitation, and granulocyte phagocytosis tests.
- Comparison of complement markers between patients with active CMV infection and controls (allograft rejection or stable phase).
Main Results:
- Elevated C3d and C3a des arg levels were observed during active CMV infection (P < 0.01).
- Decreased alternative pathway hemolytic activity (AP50) was found in 8/12 CMV-infected patients.
- Circulating immune complexes were detected in 15/20 CMV-infected patients, but complement activation preceded their appearance.
Conclusions:
- Active CMV infection in renal transplant patients is associated with complement activation and formation of C3a des arg.
- Findings suggest the alternative complement pathway is involved, indicated by decreased AP50 and normal/high C4 levels.
- Complement activation in CMV infection appears independent of classical pathway activation by immune complexes.
Abstract:
In 32 patients with a renal allograft, serial determinations after transplantation were made of C3d, the stable conversion product of the complement factor C3, as well as serial measurements of the anaphylatoxin C3a des arg. Furthermore, serial determinations were made on the presence of circulating immune complexes using three different assays (C1q binding assay, polyethylene glycol precipitation test, and indirect granulocyte phagocytosis test). Twenty patients were studied during an active cytomegalovirus (CMV) infection, and 12 patients were studied during allograft rejection or during stable phase after renal transplantation. In 12 patients with a CMV infection serial measurements were made of AP50 (alternative pathway of complement). During an active CMV infection elevated C3d as well as elevated C3a des arg levels were found and not in the control group (P less than 0.01). In 8 out of the 12 patients tested, with CMV infection, a decreased hemolytic activity of the alternative pathway (AP50) was found, together with the elevated levels of C3d and C3a des arg. Serum C4 levels were normal or high during CMV infection. Furthermore, circulating immune complexes were found to be positive in 15 out of the 20 patients with a CMV infection (both primary and secondary infections), and in 2 out of 12 patients of the control group. The complement activation found in the CMV group was not related to the presence of circulating immune complex-like material, since complement activation was present in advance of the appearance of the immune complexes, suggesting that complement activation was not due to classical pathway activation by those complexes. We conclude that our data are consistent with complement activation and the formation of biologically active peptides like C3a des arg in patients with an active CMV infection. The decreased hemolytic activity of the alternative pathway (AP50) together with the normal or high C4 levels suggest involvement of the alternative pathway, although further studies of the alternative pathway of C are warranted to confirm this hypothesis.