HLA-DQ in Acute Kidney Transplantation Rejection

NCT ID: NCT03896919

Last Updated: 2020-05-19

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-05-05
• Study Completion Date: 2020-05-12

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.

Conditions

Kidney Transplantation

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

cases

HLA-DQ mismatched recipient-donor pairs

HLA-DQ by luminex technology in kidney transplantation

Intervention Type: DIAGNOSTIC_TEST

HLA typing (DQ) for donor and recipient using Luminex microbead method from EDTA blood sample

control

HLA-DQ matched recipient- donor pairs

HLA-DQ by luminex technology in kidney transplantation

Intervention Type: DIAGNOSTIC_TEST

HLA typing (DQ) for donor and recipient using Luminex microbead method from EDTA blood sample

Interventions

HLA-DQ by luminex technology in kidney transplantation

HLA typing (DQ) for donor and recipient using Luminex microbead method from EDTA blood sample

Intervention Type: DIAGNOSTIC_TEST

Eligibility 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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Assiut University

OTHER

Sponsor Role: lead

Responsible Party

Maha Gamal Ahmed

principle investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

sohair k sayed, prof.doctor

Role: STUDY_DIRECTOR

clinical pathology

Locations

Assiut U

Asyut, , Egypt

Countries

Egypt

Related Links

https://www.ncbi.nlm.nih.gov/pubmed?cmd=search&term=HOD+T%5Bau%5D&dispmax=50

Clinical issues in renal transplantation in the elderly. Clin Transplant 2015; 29: 167-175

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862565/

The association between broad antigen HLA mismatches, eplet HLA mismatches and acute rejection after kidney transplantation. Transplant Direct 2: e120, 20

https://www.ncbi.nlm.nih.gov/pubmed/22622504

donor-specific HLA-DQ antibodies may contribute to poor graft outcome after renal transplantation. Kidney Int 82: 598-604, 2012 .

Other Identifiers

HLA-DQ in kidney transplant.

Identifier Type: -

Identifier Source: org_study_id