HLA-DQ in Acute Kidney Transplantation Rejection
Study Details
Study Description
Brief Summary
- Study the impact of HLA-DQ mismatch on acute rejection of Kidney transplantation
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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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 Design
Arms and Interventions
| Arm | 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
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
- The patients who will receive renal transplants.
Exclusion Criteria:
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Recipients with pre-transplantation desensitization protocols.
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Recipients with history of previous transplant or pregnancy.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Assiut U | Assiut | Egypt |
Sponsors and Collaborators
- Assiut University
Investigators
- Study Director: sohair k sayed, prof.doctor, clinical pathology
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- 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 .
Publications
None provided.- HLA-DQ in kidney transplant.