Acute graft versus host disease remains a major cause of morbidity and mortality in allogeneic bone marrow transplantation. To date, no clinically useful test has been reported that will predict the occurrence of graft versus host disease in genotypic HLA-identical donor-recipient pairs. We have developed a skin-explant model using donor lymphocytes that have been sensitized against recipient lymphocytes in vitro and cocultured with the recipient's skin. Histologic changes compatible with acute graft versus host disease are found in the positive explants. To date 32 patients have been tested in a prospective manner. Among the 18 recipient-donor pairs that were positive, 16 patients were found to have histologic Grade 2 or higher graft versus host disease of the skin on biopsy. Among the 14 negative pairs, only 3 patients had histologic Grade 2 or higher graft versus host disease of the skin on biopsy. Thus, the model has a sensitivity of 84 per cent and a specificity of 85 per cent, and is a significant predictor of the histologic occurrence of graft versus host disease (P less than 0.0005 by chi-square test). The test may be useful in the selection of donors for bone marrow transplantation and in the planning of prophylaxis against graft versus host disease.
This article has been cited by other articles:
Mathers, A. R., Janelsins, B. M., Rubin, J. P., Tkacheva, O. A., Shufesky, W. J., Watkins, S. C., Morelli, A. E., Larregina, A. T.
(2009). Differential Capability of Human Cutaneous Dendritic Cell Subsets to Initiate Th17 Responses. J. Immunol.
182: 921-933
[Abstract][Full Text]
Dean, R. M., Fry, T., Mackall, C., Steinberg, S. M., Hakim, F., Fowler, D., Odom, J., Foley, J., Gress, R., Bishop, M. R.
(2008). Association of Serum Interleukin-7 Levels With the Development of Acute Graft-Versus-Host Disease. JCO
26: 5735-5741
[Abstract][Full Text]
Haniffa, M. A., Wang, X.-N., Holtick, U., Rae, M., Isaacs, J. D., Dickinson, A. M., Hilkens, C. M. U., Collin, M. P.
(2007). Adult Human Fibroblasts Are Potent Immunoregulatory Cells and Functionally Equivalent to Mesenchymal Stem Cells. J. Immunol.
179: 1595-1604
[Abstract][Full Text]
Sackstein, R., Messina, J. L., Elfenbein, G. J.
(2003). In vitro adherence of lymphocytes to dermal endothelium under shear stress: implications in pathobiology and steroid therapy of acute cutaneous GVHD. Blood
101: 771-778
[Abstract][Full Text]
Jarvis, M, Schulz, U, Dickinson, A M, Sviland, L, Jackson, G, Konur, A, Wang, X N, Hromadnikova, I, Kolb, H J, Eissner, G, Holler, E
(2002). The detection of apoptosis in a human in vitro skin explant assay for graft versus host reactions. J. Clin. Pathol.
55: 127-132
[Abstract][Full Text]
Johnsen, H. E., Theobald, M.
(1993). Predictors of Acute Graft-versus-Host Disease in Bone Marrow Transplantation between HLA-Identical Siblings. NEJM
328: 1497-1498
[Full Text]
Horn, T. D., Rest, E. B., Karp, J. E., Burke, P. J., Vogelsang, G. B., Boucher, C. L., Hood, A. F.
(1991). Interleukin 2 and Granulocyte-Macrophage Colony-Stimulating Factor Induce a Perivascular Lymphocytic Infiltrate in a Skin Explant Model. Arch Dermatol
127: 1789-1793
[Abstract]
Kirkpatrick, C. H.
(1987). Transplantation Immunology. JAMA
258: 2993-3000
[Abstract]