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

Completed

• Conditions: Liver Transplant Rejection

• Registration Number: NCT06060808
• Lead Sponsor: Helwan University

Brief Summary

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.

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 Timeline

• Study Start: 2021-03-15
• Primary Completion: 2023-04-23
• Study Completion: 2023-07-24
• Status Verified: 2023-09
• Study First Submitted: 2023-09-24
• Study First Submitted QC: 2023-09-24
• Last Update Submitted: 2023-09-24
• Study First Posted: 2023-09-29
• Last Update Posted: 2023-09-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 105

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
gene polymorphism	baseline	gene polymorphism of NFKBIA and PTPN22 genes

Secondary Outcome Measures

Name	Time	Method
immunosuppressant levels	14 days	tacrolimus,cycosporin,evrolimus trough levels

Trial Locations

Locations (1)

Sara Mohamed Mohamed; 🇪🇬 Cairo, Egypt