ABSTRACT
TGF-ß1 is a cytokine with profibrogenic and immunosuppressive activities, which suggest the clinical significance of TGF-ß1 for the assessment of graft function after LT. We analyzed the dynamics of TGF-ß1 levels in the blood after LDLT in 135 pediatric liver recipients and examined the relationship between the cytokine levels and the laboratory and clinical variables. We found that TGF-ß1 levels in the blood of patients with ESLD were lower than that in healthy children of the same age, P = .001. Moreover, blood levels of TGF-ß1 were associated with liver disease etiology (r = .23) and hepatic fibrosis severity (r = .33). Before LDLT, TGF-ß1 levels were significantly higher in children with good outcomes than in recipients who developed graft dysfunction early in the post-transplant period, P = .047. One month after LDLT, TGF-ß1 levels in blood plasma increased in pediatric recipients, P = .002. Cytokine levels were significantly correlated with gender (r = .21) and HLA (r = -.24) mismatches, as well as with TAC dosage (r = -.32) later in the post-transplant period. One year after LDLT, TGF-ß1 plasma levels were higher (P = .01) than those before LDLT and did not correlate with most of the investigated biochemical and clinical variables. Conclusion: Blood levels of TGF-ß1 are associated with hepatic fibrosis severity, graft dysfunction development, and TAC dosage and can be regarded as a potential prognostic biomarker for the assessment of graft function and the optimization of immunosuppressant dosage in pediatric recipients after LDLT.
Subject(s)
End Stage Liver Disease/surgery , Liver Transplantation , Postoperative Complications/diagnosis , Transforming Growth Factor beta1/blood , Biomarkers/blood , Case-Control Studies , Child , Child, Preschool , Delayed Graft Function/blood , Delayed Graft Function/diagnosis , Delayed Graft Function/prevention & control , End Stage Liver Disease/blood , End Stage Liver Disease/diagnosis , Female , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Infant , Male , Postoperative Complications/blood , Postoperative Complications/prevention & control , Postoperative Period , Preoperative Period , Retrospective Studies , Treatment OutcomeABSTRACT
Mutations in DES, encoding desmin protein, are associated with different kinds of skeletal and/or cardiac myopathies. However, it is unknown, whether DES mutations are associated with left ventricular hypertrabeculation (LVHT). Here, we performed a clinical examination and subsequent genetic analysis in a family, with two individuals presenting LVHT with conduction disease and skeletal myopathy. The genetic analysis revealed a novel small in-frame deletion within the DES gene, p.Q113_L115del, affecting the α-helical rod domain. Immunohistochemistry analysis of explanted myocardial tissue from the index patient revealed an abnormal cytoplasmic accumulation of desmin and a degraded sarcomeric structure. Cell transfection experiments with wild-type and mutant desmin verified the cytoplasmic aggregation and accumulation of mutant desmin. Cotransfection experiments were performed to model the heterozygous state of the patients and revealed a dominant negative effect of the mutant desmin on filament assembly. DES:p.Q113_L115del is classified as a pathogenic mutation associated with dilated cardiomyopathy with prominent LVHT.