Genetic variants of innate immune receptors and infections after liver transplantation

Abstract

Infection is the leading cause of complication after liver transplantation, causing morbidity and mortality in the first months after surgery. Allograft rejection is mediated through adaptive immunological responses, and thus immunosuppressive therapy is necessary after transplantation. In this setting, the presence of genetic variants of innate immunity receptors may increase the risk of post-transplant infection, in comparison with patients carrying wild-type alleles. Numerous studies have investigated the role of genetic variants of innate immune receptors and the risk of complication after liver transplantation, but their results are discordant. Toll-like receptors and mannose-binding lectin are arguably the most important studied molecules; however, many other receptors could increase the risk of infection after transplantation. In this article, we review the published studies analyzing the impact of genetic variants in the innate immune system on the development of infectious complications after liver transplantation.

Impact of MBL2 gene polymorphisms on the risk of infection in solid organ transplant recipients: A systematic review and meta-analysis

“…Four further articles were manually identified from reference lists. After removing of duplicate studies and detailed evaluation of titles and abstracts, 45 articles were fully assessed for eligibility . Eleven studies (Table ) fulfilled the inclusion and exclusion criteria and were finally included in the present study (PRISMA flow chart shown in Figure ).…”

“…Genetic susceptibility to infection among SOT recipients appears to be driven by a number of allelic variants in genes orchestrating innate and adaptive immune responses, whose clinical impact may be at least partially unmasked by the effect of posttransplant immunosuppression. In the present meta‐analysis comprising 11 studies and more than 1800 SOT recipients we observed that, as compared to high‐MBL expression haplotypes (YA/YA or YA/XA), the risk of posttransplant bacterial and fungal infections significantly increases by 30% in the presence of any MBL‐deficient haplotype.…”

“…Both dominant and recessive genetic models were evaluated for each single SNP. The heterogeneity assumption was evaluated by the chi‐square‐based Cochran's Q test (which was considered significant at P < .05) and quantified with the I statistic (with values <25%, 25% to 75%, and >75% interpreted as representing low, moderate, and high levels of heterogeneity, respectively). Random‐effects model with the Mantel‐Haenszel method was used for pooling results from primary studies in the presence of significant heterogeneity; otherwise, a fixed‐effects model was applied.…”

“…Long‐term immunosuppression administered to solid organ transplant (SOT) recipients is associated with an increased risk of infectious complications. Current immunosuppressive drugs are mostly aimed at suppressing T cell–mediated adaptive immunity, potentially giving innate immunity a crucial role in protecting against pathogens in the transplant setting …”

“…The presence of low or deficient serum MBL levels has been associated with an increased risk of infectious complications after SOT, particularly for cytomegalovirus (CMV) infection, although discrepant results can be also found . In view of the major role played by genetic determinants, the potential impact of variant alleles or haplotypes of SNPs located in the MBL2 gene has also been investigated, with most but not all studies reporting an association with the occurrence of posttransplant infection.…”