HLA-DQ in Acute Kidney Transplantation Rejection

Completed

• Conditions: Kidney Transplantation

• Registration Number: NCT03896919
• Lead Sponsor: Assiut University

Brief Summary

- Study the impact of HLA-DQ mismatch on acute rejection of Kidney transplantation

Detailed Description

Introduction Human Leukocyte Antigens (HLA). The major histocompatibility complex (MHC) is a gene region coding for cell surface proteins important for the immune system. MHC is the most complex immunogenetic system presently known in humans . HLA are groups of cell surface proteins encoded by genes in MHC which are known as HLA in humans and H-2 in mice .

HLA genes are located on the short arm of chromosome 6 at 6p21 position , occupying a genetic region of 4Mbps. The human immune system uses HLA's uniqueness to distinguish self from non-self. HLA are responsible for the presentation of "foreign" peptides (antigens) to the immune competent cells. T lymphocytes recognize foreign antigens only when it combines with HLA molecules.

Humans have three class I HLA (A, B, C) that are present on all nucleated cells and six class II HLA (DPA1, DPB1, DQA1, DQB1, DRA, DRB1) that are present only on antigen-presenting cells and lymphocytes. Three of the seven heterodimers (HLA-A, -B, and -DRB1) contribute to the majority of immunogenicity of mismatched antigens and therefore traditional HLA-typing methods have primarily focused on these alleles .

Renal transplantation is the gold standard therapeutic strategy of replacing renal dysfunctions that offers the best survival to the patients with end-stage renal disease (ESRD). Kidney transplantation is associated with 68% lower risk of death than dialysis . Graft and patient survival after kidney transplantation have improved over the past decade. Death-censored graft survival has increased steadily over the past decade in both adults and pediatric recipients. Data provided by the Scientific Registry of Transplant Recipients (SRTR) demonstrate a 10-year overall graft survival for both living and deceased donors of approximately 55 to 60 percent compared with 35 to 40 percent from a decade prior .

Renal transplantation success is dependent on the reaction of the immune system primarily against human leucocyte antigen (HLA) proteins of the transplant. Patients previously exposed to non-self HLA through transplant, blood transfusions or pregnancy may develop antibodies reactive to HLA .

HLA matching provides benefits in improving outcomes in kidney transplantation and remains part of the kidney allocation. HLA-DR matching has a much greater effect on graft outcomes compared with matching at the HLA-A or -B locus.

Although HLA-DQ does not factor into organ allocation, its relative importance has been increasingly recognized. Recipients with de novo anti-DQ donor-specific antibodies have a higher incidence of acute rejection, transplant glomerulopathy, and graft loss . The effect of broad antigen HLA-DQ mismatching on kidney transplantation has not been clearly established. Although older studies found no significant correlation between HLA-DQ mismatching and graft outcomes , more recent data from the Australia and New Zealand Dialysis and Transplant Registry suggested that HLA-DQ mismatching affects outcomes .

Broad antigen HLA-DQ matching between each recipient and donor on the basis of serologic typing is available for the majority of kidney transplant recipients in the United Network for Organ Sharing (UNOS) registry . Using UNOS data, the investigators sought to determine the effect of HLA-DQ matching on acute rejection and graft loss after kidney transplantation.

Study Timeline

• Study First Submitted: 2019-03-26
• Study First Submitted QC: 2019-03-28
• Study First Posted: 2019-04-01
• Study Start: 2019-05-05
• Status Verified: 2020-05
• Primary Completion: 2020-05-05
• Study Completion: 2020-05-12
• Last Update Submitted: 2020-05-17
• Last Update Posted: 2020-05-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• The patients who will receive renal transplants.

Exclusion Criteria

• Recipients with pre-transplantation desensitization protocols.
• Recipients with history of previous transplant or pregnancy.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Combined incidence of DSA or IA on peripheral blood molecular profiling	Baseline	DSA considered as a binary variable (positive or negative), with positivity based on a threshold criteria of Mean Fluorescence Intensity (MFI) approaching 1000. IA will be considered present or absent using a molecular assay.

Secondary Outcome Measures

Name	Time	Method
Incidence of HLA-DQ DSA [ Time Frame: assessed at days 3,7,15,30 post transplantation	baseline	Human Leukocyte Antigen, Class II, DQ locus DSA (HLA-DQ DSA). Assessed in subjects who are DSA positive

Trial Locations

Locations (1)

Assiut U; 🇪🇬 Assiut, Egypt