ABSTRACT
INTRODUCTION: We studied the influence of a broad range of genetic variants in recipient and donor innate immunity receptors on bacterial and fungal infections and acute rejection after liver transplantation (LT). METHODS: Seventy-six polymorphisms in TLR 1-10, NOD2, LBP, CD14, MD2, SIGIRR, Ficolins 1, -2, and -3, MASP 1, -2, and -3, and the complement receptor C1qR1 were determined in 188 LT recipients and 135 of their donors. Associations with clinically significant infections and acute rejection were analyzed for 50 polymorphisms. Significant associations were validated in an independent cohort of 181 recipients and 167 donors. RESULTS: Three recipient polymorphisms and 3 donor polymorphisms were associated with infections in the identification cohort, but none of these associations were confirmed in the validation cohort. Three donor polymorphisms were associated with acute rejection in the identification cohort, but not in the validation cohort. CONCLUSION: In contrast to their effect in the general population, 50 common genetic variations in innate immunity receptors do not influence susceptibility to bacterial/fungal infections after LT. In addition, no reproducible associations with acute rejection after LT were observed. Likely, transplant-related factors play a superior role as risk factors for bacterial/fungal infections and acute rejection after LT.
Subject(s)
Bacterial Infections/genetics , Immunity, Innate/genetics , Liver Transplantation , Mycoses/genetics , Polymorphism, Genetic , Postoperative Complications , Receptors, Immunologic/genetics , Adolescent , Adult , Aged , Bacterial Infections/immunology , Child , Cohort Studies , Female , Genotyping Techniques , Graft Rejection/genetics , Graft Rejection/immunology , Humans , Male , Middle Aged , Mycoses/immunology , Predictive Value of Tests , Risk Factors , Tissue Donors , Young AdultABSTRACT
A subset of pancreatic cystic neoplasms are regarded as precursor lesions of pancreatic cancer, but only a minority of all pancreatic cystic neoplasms will undergo malignant transformation. MicroRNAs are increasingly recognized as molecular targets in carcinogenesis. Previously, a 9-microRNA (miR) signature was suggested to discriminate between high risk and low risk pancreatic cystic neoplasm. In this study, we aimed to validate this 9-miR panel in a prospective cohort. Total miR was isolated from pancreatic cyst fluid and expression of miR18a, miR24, miR30a-3p, miR92a, miR99b, miR106b, miR142-3p, miR342-3p, and miR532-3p was analyzed by singleplex Taqman MicroRNA Assay. A total of 62 patient samples were analyzed. During follow-up, 24 (38.7%) patients underwent resection, of which 6 (9.7%) patients showed at least high grade dysplasia. A logistic regression model presented a "predicted risk" score which significantly differed between low and high risk cysts, either including all patients or only those with histological confirmation of diagnosis. Using a set cut-off of 50%, the sensitivity of the model for the total cohort was 10.0%, specificity 100.0%, positive predicted value 100.0%, negative predicted value 85.2%, and diagnostic accuracy of 85.5%. Thus, while observing a significant difference between low and high risk cysts, clinical implementation of this biomarker panel is as yet unlikely to be beneficial in the management of pancreatic cysts.