Mannose-Binding Lectin Serum Levels and Pre-Tranplant Genotypes for Personalized Anti-CMV Prophylaxis in Heart Recipients

Very few studies of innate immunity have been performed to identify potential risk factors for development of infection in heart recipients. Among these markers, gene polymorphisms leading to lower serum levels of mannose-binding lectin (MBL), have been associated with an increased risk of infections in other clinical settings. We aimed to evaluate the relationship between serum MBL concentration and functionally relevant MBL2 gene polymorphisms and development of severe infections in heart recipients. 72 adult heart recipients were evaluated. One-year clinical follow-up was performed after transplantation. Universal prophylaxis with gancyclovir was administered. CMV antigenemia and PCR were prospectively evaluated. MBL serum concentration was evaluated by a commercial ELISA test. MBL2 single nucleotide polymorphisms were genotyped using a sequence-based typing technique in 61 patients. Time of studies: baseline (at the time of inclusion in the waiting list), day 7 and day 30 after transplantation. The distribution of MBL genotype was as follows: High (n=36), intermediate (n=16) and low (n=9). There was a good correlation between the MBL genotype and serum concentrations of MBL that were significantly lower in patients with low and intermediate genotype as compared with patients with high MBL genotype at all study points. Lower concentrations of serum MBL (below the mean value as a cut-off) were a risk factor for development of: Recurrent severe infections (day 7 <1378, relative risk [RR] 6.16, 95%CI 1.20-31.8, p=0.03; day 30 <1128, RR 6.74, 1.30-34.9, p=0.02), CMV infection (day 7 <1378, RR 4.63, 1.11-19.25, p=0.03; day 30 <1128, RR 4.62, 1.11-19.15, p=0.03). Low or intermediate MBL genotypes were more frequently observed among patients who developed CMV infection during the first year after transplantation as compared with patients who did not develop CMV infection (RR 6.47, 1.33-31, p=0.02). The distribution of low, intermediate or high-MBL genotypes polymorphism had no impact on the rate of other infectious outcomes including overall severe infections, bacterial infections and fungal infections. Lower concentrations of MBL and the presence of low or intermediate MBL-producing genotypes were risk factors for development of CMV infection in heart recipients.