Complement-activating Anti-human Leucocyte Antigen Donor Specific Antibodies in Solid Organ Transplantation: A Systematic Review and Meta-analysis
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 7,547
- Primary Endpoint
- Allograft Survival rate
Study Overview
Brief Summary
This project will involve a systematic literature review and meta-analysis of studies assessing the impact of complement-activating anti-Human Leukocyte Antigen (HLA) donor specific antibodies (DSA) on the allograft survival rate and on the rejection rate.
This meta-analysis will assess the role of complement activating anti-HLA DSAs across the entire transplant field including kidney, liver, lung and heart transplant recipient's studies.
Detailed Description
BACKGROUND:
Organ transplantation has emerged as the treatment of choice for patients with end-stage chronic disease, which is an increasing burden in industrialized and newly-industrializing societies. For example, the global burden of end-stage renal disease in 2017 is estimated to be 3,900,000 with an ~6% growth rate, which is significantly greater than world population growth. Today, over one million people worldwide live with organ transplants, and another 120,000 organs transplanted each year.
Despite progress in transplantation, allograft rejection remains a major threat to allograft health, with thousands of allografts failing every year worldwide due to organ rejection. Failed allografts create immediate and severe consequences for patients in terms of mortality and morbidity, while generating billions in extra costs to health care systems.
One of the most important advances in transplant medicine was the recognition that anti-human lymphocyte antigen (anti-HLA) antibodies are destructive. Recently, lots of studies recognized the capacity of anti-HLA antibodies to activate complement and determined that complement activation magnifies the cytotoxic potential of these antibodies. Over the last decade, studies have reported that complement-activation is highly associated with allograft rejection and failure, with varying magnitudes of effect. In addition, more recent studies have suggested that beyond kidney allografts, these antibodies could have a broad universal deleterious effect in other solid organ transplants such a heart, liver and lung allografts.
MAIN OUTCOMES AND MEASURES:
Study Design
- Study Type
- Observational
- Observational Model
- Other
- Time Perspective
- Retrospective
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Study design:
- •Studies of any relevant design and in any language on the impact of complement-activating anti-HLA DSAs on long-term graft survival and/or the risk of rejection will be initially selected.
- •eligible studies: The eligible studies include all solid organ transplant patients (kidney, liver, lung, heart, and intestinal transplantation), both adult or paediatric patients.
- •Measurement:
- •Anti-HLA DSAs detect by the single antigen Luminex bead technique (SAB) will be required for the DSA detection technique. Complement-activating anti-HLA DSAs will be defined according to their ability to bind C1q, C3d, and C4d or their IgG3 subclass.
Exclusion Criteria
- •Animal studies
- •Ex vivo studies
- •Methodological studies
Outcomes
Primary Outcomes
Allograft Survival rate
Time Frame: death censored allograft survival at minimum 1 year of follow up
To assess the impact of complement-activating anti-Human Leukocyte Antigen (HLA) donor specific antibodies (DSA) on the allograft survival rate in solid organ transplant patients (Heart, Kidney, Lung, Liver and Small Bowel transplant recipients)
Secondary Outcomes
- Allograft Rejection rate(rejection rate during follow up (at minimum 3 months post transplantation) or rejection defined by biopsy at inclusion)
Investigators
Professor Alexandre Loupy
Professor Alexandre Loupy
Paris Translational Research Center for Organ Transplantation