NDT Advance Access published June 24, 2008 Nephrol Dial Transplant (2008) 1 of 7 doi: 10.1093/ndt/gfn355
Original Article
Impact of the complement lectin pathway on cytomegalovirus disease early after kidney transplantation Solbjørg Sagedal1 , Steffen Thiel2 , Troels Krarup Hansen3 , Tom Eirik Mollnes4 , Halvor Rollag5 and Anders Hartmann6 1
Department of Nephrology, Ullev˚al University Hospital, Oslo, Norway, 2 Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark, 3 The Medical Research Laboratories, Clinical Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark, 4 Institute of Immunology, 5 Institute of Medical Microbiology and 6 Department of Internal Medicine and Laboratory for Renal Physiology, University of Oslo and Rikshospitalet University Hospital, Oslo, Norway
Correspondence and offprint requests to: Solbjørg Sagedal, Department of Nephrology, Ullev˚al University Hospital, 0407 Oslo,Norway. Tel: +47-22-11-91-01; Fax: +47-22-11-91-81; E-mail:
[email protected]
However, low MASP-2 levels may play a role in the development of symptomatic CMV disease. Keywords: complement; cytomegalovirus infection; kidney transplantation; mannose-binding lectin; MASP-2
Introduction Mannose-binding lectin (MBL) is a serum protein that recognizes molecular patterns on microbial surfaces and may also in certain situations bind to altered self-surfaces [1]. In serum, MBL is bound to structurally related proteins, the MBL-associated serine proteases (MASPs) 1, 2 and 3, as well as to the protein MAp19. MASP-2 circulates in plasma in complexes with MBL and with L- and H-ficolin [2]. The binding of MBL or ficolin to microbes activates MASP-2, which then cleaves C4 and C2 to generate the C3 convertase, thereby initiating the lectin pathway of complement activation. Thus, MASP-2 represents the effector component of complement activation for MBL and ficolins. MASP-1 might also be implicated in lectin pathway activation, whereas the roles of MASP-3 and MAp19 are less well known [2]. MBL deficiency is under certain conditions associated with repeated infections both in children and adults [3,4]. The clinical significance of MASP-2 deficiency has only recently started to be studied. One case report describes MASP-2 deficiency in a patient with recurrent severe infections and autoimmune reactions [5]. Another study found MASP-2 deficiency as a risk factor for fever episodes in children undergoing chemotherapy [6]. The lectin pathway of complement activation is antibody independent and seems to be involved in several types of virus infections. For instance, studies on influenza A virus have indicated that MBL may perform direct viral
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Abstract Background. This study retrospectively investigated the association between pre-transplant levels of mannosebinding lectin (MBL) plus the associated serine protease (MASP)-2 and the occurrence of cytomegalovirus (CMV) infection and symptomatic CMV disease during the first 12 weeks after kidney transplantation. Materials and methods. Altogether 159 consecutive single kidney transplant recipients were included. The patients were screened for CMV pp65 antigenaemia every second week. No CMV prophylaxis or pre-emptive treatment was given. MBL and MASP-2 were measured in samples taken at transplantation and 10 weeks later. Results. CMV infection, defined as at least one positive test, was found in 95 patients (59.8%). MBL and MASP-2 measured at transplantation were similar in patients with and without CMV infection. The incidence of CMV infection was also similar in 36 patients (58.3%) with pretransplant MBL levels below the reference level (500 µg/L) and in patients with higher MBL levels (60.2%). Symptomatic CMV disease was diagnosed in 35 patients (22%), and MASP-2 levels at transplantation in the lower quartile range (≤148 µg/L) was significantly associated with CMV disease during the first 12 weeks, P = 0.028. MBL levels decreased significantly from transplantation to 10 weeks later, and median (interquartile range) fell from 2597 (526–4939) µg/L to 1520 (270–3069) µg/L (P < 0.001). In contrast, MASP-2 levels increased significantly from 252 (148–382) µg/L to 380 (302–492) µg/L (P < 0.001). Conclusion. Pre-transplant MBL levels do not influence the incidence of any CMV infection or symptomatic CMV disease during the first 12 weeks after kidney transplantation.
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Table 1. Baseline characteristics and risk factors (n = 159)
Recipient-related factors Recipient age Female Cold ischaemia Time (h) Acute rejection MBL at tx (µg/L) MASP-2 at tx (µg/L) hs CRP at tx (mg/L) Donor-related factors Donor age Living
CMV infection +
CMV infection −
P
All
99 50 (16) 28 (28.3%) 8.2 (1.2 to 17.3)
60 42 (15) 20 (33.3%) 2.6 (
