Abstract
BackgroundAlthough liver transplantation is one of the most efficient curative therapies of end stage liver diseases, recipients may suffer liver graft loss opst-operation. IRF-5, a member of Interferon Regulatory Factors, functions as a key regulator in TLR4 cascade, and is capable of inducing inflammatory cytokines. Although TLR4 has been proved to contribute to acute allograft rejection, including after liver transplantation, the correlation between IRF5 gene and acute rejection has not been elucidated yet.MethodsThe study enrolled a total of 289 recipients, including 39 females and 250 males, and 39 recipients developed acute allograft rejection within 6 months post-transplantation. The allograft rejections were diagnosed by liver biopsies. Genome DNA of recipients was extracted from pre-operative peripheral blood. Genotyping of IRF-5, including rs3757385, rs752637 and rs11761199, was performed, followed by SNP frequency and Hardy-Weinberg equilibrium analysis.ResultsThe genetic polymorphism of rs3757385 was found associated with acute rejection. G/G homozygous individuals were at higher risk of acute rejection, with a P value of 0.042 (OR = 2.34 (1.07–5.10)).ConclusionsIRF5, which transcriptionally activates inflammatory cytokines, is genetically associated with acute rejection and might function as a risk factor for acute rejection of liver transplantations.
Highlights
Liver transplantation has been accepted worldwide as an efficient way of treating end stage liver diseases and acute liver failure
The total incidence of allograft rejection decreases dramatically due to immunosuppressive therapies [3], acute rejection episodes still occur among 15–45% recipients within several months, which leads to higher incidence of chronic organ dysfunction and suboptimal long-term outcomes [3]
We first analyzed the clinical data from individuals, and no statistical significance was found among age, gender, Model For End-Stage Liver Disease (MELD) score and most of the primary diagnoses, except Hepatitis B Virus (HBV) infection (Table 1)
Summary
Liver transplantation has been accepted worldwide as an efficient way of treating end stage liver diseases and acute liver failure. It is gradually accepted that, by responding to the released danger signal, innate immune reaction functions as a pivotal trigger in acute rejection [4]. Toll-like Receptors (TLR), which recognize pathogen-associated molecular patterns (PAMP) on microorganisms in innate immune response, are proved to initiate inflammation by recognizing molecules released from damaged cells during organ transplantation [5,6], and prevent graft tolerance in dependence of type I IFNs [7]. TLRs pathway can induce immunosuppression [8,9], and we confirmed the contribution of TLR4 to liver graft rejection [10]. Regardless of enhanced alloimmune response or immunosuppression, the elucidation of TLR signal pathway in acute rejection, especially TLR4, is urgently needed. TLR4 has been proved to contribute to acute allograft rejection, including after liver transplantation, the correlation between IRF5 gene and acute rejection has not been elucidated yet
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