HLA-DQ in Acute Kidney Transplantation Rejection

Impact of HLA-DQ Mismatch on Acute Rejection of Kidney Transplantation

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

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Diagnostic test: HLA-DQ by luminex technology in 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 Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt
    • Assiut U

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study will be carried out on (30) renal transplant Recipient- Donor pairs who will be recruited from transplantation unit.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
cases; HLA-DQ mismatched recipient-donor pairs	Diagnostic test: HLA-DQ by luminex technology in kidney transplantation; HLA typing (DQ) for donor and recipient using Luminex microbead method from EDTA blood sample
control; HLA-DQ matched recipient- donor pairs	Diagnostic test: HLA-DQ by luminex technology in kidney transplantation; HLA typing (DQ) for donor and recipient using Luminex microbead method from EDTA blood sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Combined incidence of DSA or IA on peripheral blood molecular profiling	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.	Baseline

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Study Director: sohair k sayed, prof.doctor, clinical pathology

Publications and helpful links

Helpful Links

• Clinical issues in renal transplantation in the elderly. Clin Transplant 2015; 29: 167-175
• The association between broad antigen HLA mismatches, eplet HLA mismatches and acute rejection after kidney transplantation. Transplant Direct 2: e120, 20
• donor-specific HLA-DQ antibodies may contribute to poor graft outcome after renal transplantation. Kidney Int 82: 598-604, 2012 .

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 5, 2019
• Primary Completion (ACTUAL): May 5, 2020
• Study Completion (ACTUAL): May 12, 2020

Study Registration Dates

• First Submitted: March 26, 2019
• First Submitted That Met QC Criteria: March 28, 2019
• First Posted (ACTUAL): April 1, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 19, 2020
• Last Update Submitted That Met QC Criteria: May 17, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: HLA-DQ in kidney transplant.

Drug and device information, study documents

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