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A histopathologic grading system of hyperacute (humoral, antibody-mediated) cardiac xenograft and allograft rejection
1Jesse E. Edwards Registry of Cardiovascular Disease, United Hospital, St. Paul, MN 55102, USA.
Insights
A new grading system for cardiac xenograft rejection was developed, categorizing hyperacute and mixed rejection into mild, moderate, or severe stages. This system aids in evaluating vascular rejection in future xenotransplantation research.
Area of Science:
- Transplantation immunology
- Pathology
- Cardiovascular research
Background:
- Clinical xenografting requires a reproducible grading system for vascular rejection.
- Current grading systems do not formally address hyperacute or delayed vascular rejection.
- A standardized pathological evaluation is crucial for successful xenotransplantation.
Purpose of the Study:
- To define a microscopic grading system for hyperacute vascular rejection in cardiac xenografts.
- To establish a reproducible method for assessing vascular rejection in experimental and clinical settings.
- To provide a foundation for evaluating xenograft rejection in future clinical applications.
Main Methods:
- Review of clinical and histological findings from 112 cardiac xenografts and allografts.
- Analysis of histopathological features and clinical data from discordant xenografts, concordant xenografts, and allografts.
- Development of a two-category grading system (Grade A: unmodified hyperacute rejection; Grade B: mixed hyperacute and acute cellular rejection) with three stages (mild, moderate, severe).
Main Results:
- A grading system was devised to categorize samples into Grade A (unmodified hyperacute rejection) or Grade B (mixed hyperacute and acute cellular rejection).
- Both Grade A and Grade B were further subcategorized into mild, moderate, or severe stages.
- The study included a review of 112 cardiac xenografts and allografts, with a focus on vascular rejection.
Conclusions:
- A unified grading system is applicable to both hyperacute and mixed rejection scenarios.
- The proposed system facilitates meaningful pathological evaluation of hyperacute rejection.
- This grading system is essential for the clinical translation of xenografting.
Background:
If future attempts to introduce xenografting into clinical practice prove successful, it will be essential to have a clinically relevant, reproducible grading system for vascular rejection. No formal attempt has been made to grade hyperacute or delayed vascular rejection on the basis of a review of both experimental and clinical material.
Methods And Results:
In an attempt to define a microscopic grading system for hyperacute vascular rejection of the heart, we reviewed the clinical and histologic findings in 112 previously personally studied experimental (n = 109) and clinical (n = 3) cardiac xenografts and allografts, most of which showed vascular rejection. The study material comprised 44 discordant xenografts, 41 concordant xenografts, and 27 allografts. We documented, analyzed, and grouped the histopathologic features together with the clinical data. We devised a grading system which allowed us to allocate each sample to one of the following two categories: grade A: unmodified hyperacute rejection; grade B: mixed hyperacute and acute cellular rejection. Both grades A and B can be subcategorized into three stages: (1) mild (initial), (2) moderate (intermediate), or (3) severe (late) stage.
Conclusions:
A common grading system can be applied to both hyperacute rejection and mixed (hyperacute and acute) rejection. The proposed grading system provides a basis for meaningful pathologic evaluation of hyperacute rejection.