Microchimerism and rejection: a meta-analysis
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Aims:
To study the relationship between graft rejection and microchimerism with and without donor bone marrow infusion in recipients of kidney, liver, heart and lung transplants. Selection of manuscripts. Thirty-seven manuscripts presenting clinical data on microchimerism and rejection, published between 1991 and 1997, were identified. Of these, 16 were excluded due to duplication or insufficient data. Inclusion criteria were data on microchimerism, bone marrow infusion and rejection episodes.
Statistical Tests:
A mixed effect logistic model was used to test for homogeneity of transplant centers. The centers were found to be homogeneous for rejection rates controlling for microchimerism and bone marrow infusion. Using rejection episodes at 3, 6, and 12 months post-transplant as the outcome, we evaluated logistic regression models to derive odds ratios for rejection with microchimerism and with bone marrow infusion for each organ.
Results:
Microchimerism was generally associated with a higher incidence of acute rejection for heart, lung, and kidney transplants and a lower incidence for liver transplants, especially at 12 months and above. Bone marrow infusion decreased the risk of acute rejection for heart transplants and increased the risk for lung and, to a lesser extent, for liver transplants. No consistent effect was seen in kidney transplants. At 12 months and longer, microchimerism was associated with a decreased incidence of chronic rejection in recipients of lung transplants, but there were insufficient data to determine this outcome for other organs.
Conclusions:
(i) Microchimerism was detected in the majority of patients. (ii) The effect of microchimerism and bone marrow infusion on rejection episodes varied with the organ and, for a given organ, it was time-dependent. (iii) These findings demonstrate the need for more extensive studies on microchimerism and donor-specific hyporesponsiveness.
Insights
Microchimerism impacts graft rejection differently across organs, with bone marrow infusion also showing varied effects. More research is needed to understand these complex relationships in organ transplantation.
Area of Science:
- Immunology
- Transplantation Medicine
- Cellular Biology
Background:
- Microchimerism, the presence of donor cells in recipients, is a known phenomenon post-transplantation.
- Donor bone marrow infusion is a strategy explored to improve transplant outcomes.
- Understanding the interplay between microchimerism, bone marrow infusion, and graft rejection is crucial for optimizing transplant success.
Purpose of the Study:
- To investigate the relationship between microchimerism and graft rejection in kidney, liver, heart, and lung transplant recipients.
- To assess the influence of donor bone marrow infusion on graft rejection in these transplant types.
- To analyze the time-dependent effects of microchimerism and bone marrow infusion on rejection episodes.
Main Methods:
- Systematic review and selection of 37 clinical studies published between 1991 and 1997.
- Exclusion of 16 studies due to duplication or insufficient data.
- Application of mixed-effect logistic models and logistic regression to analyze rejection rates, microchimerism, and bone marrow infusion across different organs and time points.
Main Results:
- Microchimerism was linked to increased acute rejection in heart, lung, and kidney transplants, but decreased rejection in liver transplants, particularly beyond 12 months.
- Bone marrow infusion reduced acute rejection risk in heart transplants but increased it in lung and liver transplants; its effect on kidney transplants was inconsistent.
- Microchimerism showed a trend towards decreased chronic rejection in lung transplants at 12 months and beyond, with insufficient data for other organs.
Conclusions:
- Microchimerism was prevalent in the majority of transplant recipients studied.
- The impact of microchimerism and bone marrow infusion on graft rejection is organ-specific and time-dependent.
- Further extensive research into microchimerism and donor-specific hyporesponsiveness is warranted to improve transplant outcomes.
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