Role of NFKBIA and PTPN22 Genes Polymorphism in Acute Rejection Susceptibility After Living Donor Liver Transplantation in Egyptian Patients.

Our study aimed at studying the impact of gene polymorphism of NFKBIA and PTPN22 genes on rejection episodes in liver transplant Egyptian recipients. Also assess patients' factors associated with graft rejection.

Study Overview

• Status: Completed
• Conditions: Liver Transplant Rejection
• Intervention / Treatment: Genetic: gene polymorphism

Detailed Description

Liver transplantation is considered an effective therapy for severe liver disease, but graft dysfunction occurs in up to 13% of patients during the first year following transplantation, and rises to 35% after 5 years (Keeffe, 1999; Yu et al., 2001). Graft rejection is one of the major immunological complications following liver transplantation (Zheng et al., 2006).

The nuclear factor of kappa light polypeptide gene enhancer B-cells inhibitor-alpha (NFKBIA) gene encodes a member of the nuclear factor-kappa-B inhibitor family. Polymorphisms in this gene might be associated with a susceptibility to acute rejection episodes following liver transplantation, as they may cause an increased activation level of the proinflammatory transcription factor nuclear factor of kappa light polypeptide gene enhancer in B-cells (NFκB).

NFκB translocates to the nucleus and promotes the expression of a panel of genes (Karin and Ben-Neriah, 2000). Some of these, for example interleukin-2, interleukin-6, interleukin-12 or tumor necrosis factor-alpha, play an important role in the pathogenesis of allograft rejection and the activation of the immune system in general (Wei and Zheng, 2003).

The protein tyrosine phosphatase nonreceptor 22 gene (PTPN22) encodes a strong T-cell regulator called lymphoid protein tyrosine phosphatase. Previously, PTPN22 was described as a susceptibility gene for autoimmunity because it contains single nucleotide polymorphisms (SNPs) associated with several autoimmune diseases. One SNP (rs2476601;1858G>A) has emerged as a particularly potent risk factor for autoimmunity. We address the question whether PTPN22 polymorphismsare also associated with acute rejection after liver transplantation. (Dullin et al., 2015).

• Study Type: Observational
• Enrollment (Actual): 105

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Sara Mohamed Mohamed

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with end stage liver disease(ESLD) underwent living donor liver transplantation were recruited from Ain Shams University hospitals, Cairo, Egypt.

Description

Inclusion Criteria:

• Adult Patients with ESLD were subjected to living donor liver transplantation due to different etiologies including hepatitis C virus (HCV), hepatitis B virus (HBV), autoimmune hepatitis (AIH), portal venous thrombosis (PVT), cryptogenic hepatitis, Primary sclerosing cholangitis(PSC), hepatocellular and carcinoma(HCC) were eligible for the study. Recipients received calcineurin inhibitors either tacrolimus or cyclosporine as primary immunosuppressant ± MMF or evorilumus ± MMF immediately after transplantation.

Exclusion Criteria:

• Patients were excluded if they had multi-organ transplantation, had previously received a liver transplant, or were receiving an ABO-incompatible transplant.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gene polymorphism	gene polymorphism of NFKBIA and PTPN22 genes	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
immunosuppressant levels	tacrolimus,cycosporin,evrolimus trough levels	14 days

Collaborators and Investigators

• Sponsor: Helwan University

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2021
• Primary Completion (Actual): April 23, 2023
• Study Completion (Actual): July 24, 2023

Study Registration Dates

• First Submitted: September 24, 2023
• First Submitted That Met QC Criteria: September 24, 2023
• First Posted (Actual): September 29, 2023

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 24, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: gene polymorphism
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Disease Susceptibility
• Other Study ID Numbers: gene polymorphism

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No