Simple, rapid, reproducible and biomarker-validated clinical grading system for murine models of xenogeneic graft-versus-host disease.

Abstract

Experiment models of xenogeneic graft-versus-host disease (xeno-GVHD), in which human immune cells are injected into immunodeficient mice, are increasingly used to study human immune cell behavior in vivo and to test therapeutic approaches. Today, the main, and more commonly accepted clinical parameters used to characterize xeno-GVHD are weight loss and mortality. These criteria do not provide an accurate and subtle assessment of the disease intensity, nor do they reflect the great variability of xeno-GVHD, which depends on the donor. Relying on previous work in which we described an original clinical grading system for assessing GVHD in mice, we propose an adaptation of this system for xeno-GVHD models. This simple, solid, and reproducible scoring system of xeno-GVHD is constituted of the binary (yes or no) evaluation of four easy-to-evaluate parameters that reflect the complexity of the disease without the need to sacrifice the mice. This scoring system is consistent with the gold standard histological grading of human GVHD and with numerous biomarkers characteristic of the disease. We propose this new clinical grading system to evaluate and compare the results obtained with a common tool, regardless of the experimenters and laboratories where the experiments would have been carried out and whatever the therapeutic strategy evaluated.

Background: Experiment models of xenogeneic graft-versus-host disease (xeno-GVHD), in which human immune cells are injected into immunodeficient mice, are increasingly used to study human immune cell behavior in vivo and to test therapeutic approaches. Today, the main, and more commonly accepted clinical parameters used to characterize xeno-GVHD are weight loss and mortality. These criteria do not provide an accurate and subtle assessment of the disease intensity, nor do they reflect the great variability of xeno-GVHD, which depends on the donor.

Objective: Relying on previous work in which we described an original clinical grading system for assessing GVHD in mice, we propose an adaptation of this system for xeno-GVHD models.

Study design: This simple, solid, and reproducible scoring system of xeno-GVHD is constituted of the binary (yes or no) evaluation of four easy-to-evaluate parameters that reflect the complexity of the disease without the need to sacrifice the mice.

Results: This scoring system is consistent with the gold standard histological grading of human GVHD and with numerous biomarkers characteristic of the disease.

Conclusion: We propose this new clinical grading system to evaluate and compare the results obtained with a common tool, regardless of the experimenters and laboratories where the experiments would have been carried out and whatever the therapeutic strategy evaluated.