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HLA-DQ in Acute Kidney Transplantation Rejection

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ClinicalTrials.gov Identifier: NCT03896919
Recruitment Status : Not yet recruiting
First Posted : April 1, 2019
Last Update Posted : April 1, 2019
Sponsor:
Information provided by (Responsible Party):
Maha Gamal Ahmed, Assiut University

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

Condition or disease Intervention/treatment
Kidney Transplantation 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.


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Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Impact of HLA-DQ Mismatch on Acute Rejection of Kidney Transplantation
Estimated Study Start Date : November 2019
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Combined incidence of DSA or IA on peripheral blood molecular profiling [ Time Frame: 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 :
  1. Incidence of HLA-DQ DSA [ Time Frame: assessed at days 3,7,15,30 post transplantation [ Time Frame: baseline ]
    Human Leukocyte Antigen, Class II, DQ locus DSA (HLA-DQ DSA). Assessed in subjects who are DSA positive



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03896919


Contacts
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Contact: maha g Ahmed, Ass.lecturer 01014489537 doctormaha1710@gmail.com
Contact: Dalia A Nigm, Ass. Prof. 01066100185 dodonigma@yahoo.com

Sponsors and Collaborators
Assiut University
Investigators
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Study Director: sohair k sayed, prof.doctor clinical pathology

Additional Information:
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Responsible Party: Maha Gamal Ahmed, principle investigator, Assiut University
ClinicalTrials.gov Identifier: NCT03896919     History of Changes
Other Study ID Numbers: HLA-DQ in kidney transplant.
First Posted: April 1, 2019    Key Record Dates
Last Update Posted: April 1, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No