Low Pretransplantation Mannose-Binding Lectin Levels Predict Superior Patient and Graft Survival after Simultaneous Pancreas-Kidney Transplantation

Abstract

Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for patients with type 1 diabetes and renal failure. However, this procedure is characterized by a high rate of postoperative infections, acute rejection episodes, and cardiovascular mortality. The lectin pathway of complement activation contributes to cardiovascular disease in diabetes and may play an important role in inflammatory damage after organ transplantation. This study therefore sought to determine how mannosebinding lectin (MBL), a major recognition molecule of the lectin pathway of complement activation, influences outcome after SPKT. MBL serum levels were determined in 99 and MBL genotypes in 97 consecutive patients who received an SPKT from 1990 through 2000 and related to patient and graft survival. At 12 yr, cumulative death-censored kidney graft survival was 87.5% in patients with an MBL level Ͻ400 ng/ml and 74.8% in the group with MBL levels Ͼ400 ng/ml (P ϭ 0.021). Pancreas graft survival was significantly better in patients with low MBL levels (P ϭ 0.016). MBL levels Ͼ400 ng/ml were associated with a hazard ratio of 6.28 for patient death (95% confidence interval 1.8 to 20.3; P ϭ 0.003). Accordingly, survival was significantly better in recipients with MBL gene polymorphisms associated with low MBL levels. These findings identify MBL as a potential risk factor for graft and patient survival in SPKT. It is hypothesized that MBL contributes to the pathogenesis of inflammation-induced vascular damage both in the transplanted organs and in the recipient's native blood vessels.

Mannose-binding lectin levels and infections in children after allogeneic hematopoietic SCT

“…This is in agreement with our previous observation that measurement of MBL in serum is a more sensitive parameter to measure association with disease than MBL genotyping. 18 With this in mind, and in view of the negative results in our study with respect to association of MBL with infection, we did not determine MBL genotypic polymorphisms but only measured serum MBL levels.…”

Evaluation of lectin pathway activity and mannan-binding lectin levels in the course of pregnancy complicated by diabetes type 1, based on the genetic background

“…Since, as mentioned, intrauterine infections are one of the main reasons for premature deliveries, it is possible that, however rarely, higher MBL levels might be disadvantageous. Indeed, these data add to the ever-increasing number of contexts in which high MBL seems to be harmful (Berger et al 2007;Bilgin et al 2008;Fiane et al 2003;Hansen et al 2006;Hellemann et al 2007;Kilpatrick 2007;Schlapbach et al 2007). On the other hand, there are numerous reports showing an association between MBL deficiency in mothers or babies with prematurity or prenatal/perinatal infections (Annells et al 2004;De Benedetti et al 2007;Bodamer et al 2006;Frakking et al 2007).…”

Complement—here, there and everywhere, but what about the transplanted organ?

“…In a study looking at simultaneous kidney pancreas transplantation, low circulating levels of MBL were associated with good allograft outcome [55]. A different study associated low MBL levels with poor renal allograft function and survival in non-HLA sensitised patients [56].…”

“…In kidney transplants, high levels of MBL correlate with aggressive rejection and graft failure [55]. CD55 has been reported to be a marker of renal allograft survival when expressed in the peritubular capillaritis of AMR [141] that could be used as a biomarker whose presence may herald cessation of complement inhibitory treatment.…”