Polymorphisms in the lectin pathway of complement activation influence the incidence of acute rejection and graft outcome after kidney transplantation

Abstract

There are conflicting data on the role of the lectin pathway of complement activation and its recognition molecules in acute rejection and outcome after transplantation. To help resolve this we analyzed polymorphisms and serum levels of lectin pathway components in 710 consecutive kidney transplant recipients enrolled in the nationwide Swiss Transplant Cohort Study, together with all biopsy-proven rejection episodes and 1-year graft and patient survival. Functional mannose-binding lectin (MBL) levels were determined in serum samples, and previously described MBL2, ficolin 2, and MBL-associated serine protease 2 polymorphisms were genotyped. Low MBL serum levels and deficient MBL2 diplotypes were associated with a higher incidence of acute cellular rejection during the first year, in particular in recipients of deceased-donor kidneys. This association remained significant (hazard ratio 1.75, 95% confidence interval 1.18-2.60) in a Cox regression model after adjustment for relevant covariates. In contrast, there was no significant association with rates of antibodymediated rejection, patient death, early graft dysfunction or loss. Thus, results in a prospective multicenter contemporary cohort suggest that MBL2 polymorphisms result in low MBL serum levels and are associated with acute cellular rejection after kidney transplantation. Since MBL deficiency is a relatively frequent trait in the normal population, our findings may lead to individual risk stratification and customized immunosuppression.

A journey through the lectin pathway of complement—MBL and beyond

“…In particular this has been shown for common variable immunodeficiency and in cohorts of patients suffering from cystic fibrosis . Moreover, presence of MBL2 polymorphisms have consistently been associated with decreased kidney graft survival, although the pathophysiological mechanism behind this observation is still unknown …”

Pneumocystis jirovecii pneumonia in solid organ transplant recipients: a descriptive analysis for the Swiss Transplant Cohort

“…Due to the small number of cases of CMV disease, CMV infection and disease were considered together in all analyses performed for the purposes of this study. Acute rejection was defined for each organ following standard international guidelines …”

Preventive Strategies Against Cytomegalovirus and Incidence of α-Herpesvirus Infections in Solid Organ Transplant Recipients: A Nationwide Cohort Study

“…Each infection episode was validated by a transplant infectious diseases specialist at each center. Acute rejection was defined for each organ following the standard international criteria (14). Nonmucocutaneous disease was diagnosed in case of clinical manifestations involving the gastrointestinal tract (i.e.…”

“…Because only 19 patients in the preemptive approach group received a specific antiherpes prophylaxis, all D+/RÀ or R+ patients managed with a preemptive approach were analyzed as a single group, regardless of whether or not they received antiherpes prophylaxis. Acute rejection was defined for each organ following the standard international criteria (14).…”