HLA-DQ in Acute Kidney Transplantation Rejection

Study Overview
=================
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.

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

Conditions
-----------------
Kidney Transplantation

Intervention / Treatment
-----------------
* Diagnostic Test: HLA-DQ by luminex technology in kidney transplantation


Participation Criteria
=================
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.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| cases<br>HLA-DQ mismatched recipient-donor pairs | Diagnostic Test: HLA-DQ by luminex technology in kidney transplantation<br>* HLA typing (DQ) for donor and recipient using Luminex microbead method from EDTA blood sample<br>|
| control<br>HLA-DQ matched recipient- donor pairs | Diagnostic Test: HLA-DQ by luminex technology in kidney transplantation<br>* HLA typing (DQ) for donor and recipient using Luminex microbead method from EDTA blood sample<br>|

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 |