Clinical trial NCT03896919: HLA-DQ in Acute Kidney Transplantation Rejection
Official title: Impact of HLA-DQ Mismatch on Acute Rejection of Kidney Transplantation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Kidney Transplantation
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2019-04-01
Enrollment: 30
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

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.

Primary outcomes:
measure: Combined incidence of DSA or IA on peripheral blood molecular profiling
timeFrame: Baseline
Secondary outcomes:
measure: Incidence of HLA-DQ DSA [ Time Frame: assessed at days 3,7,15,30 post transplantation
timeFrame: baseline
Other outcomes:
Locations:
city: Assiut
country: Egypt
facility: Assiut U
Study officials:
affiliation: clinical pathology
name: sohair k sayed, prof.doctor
role: STUDY_DIRECTOR
References: