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Y. Ogawa, H. Kodama, K. Kameyama, K. Yamazaki, H. Yasuoka, S. Okamoto, K. Tsubota, H. Inoko, Y. Kawakami, M. Kuwana; Donor–Derived Fibroblasts in the Pathogenesis of Lacrimal Gland Chronic Graft–Versus–Host Disease . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4409.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Excessive fibrosis is a prominent histologic feature of chronic graft–versus–host disease (GVHD) following allogeneic hematopoietic stem cell transplantation, but the underlying mechanism remains unknown. We investigated whether the fibroblasts increased at the site of pathogenic fibrosis are originated from transplanted donor cells in patients with lacrimal gland chronic GVHD. Methods: Lacrimal gland biopsies were obtained from nine patients with chronic GVHD. The male–specific sequences detected by fluorescein in situ hybridization and in situ hybridization were used as markers for the donor cells in seven female patients who had received a transplant from male donors. In addition, primary fibroblast cultures were generated from lacrimal gland biopsies and examined for mismatched genetic markers between recipients and donors. Results: In seven female patients who received a sex–mismatched transplant, fluorescein in situ hybridization for the Y–chromosome showed that 13·4–26·7% of fibroblasts accumulated in the lacrimal gland tissue were donor–derived. The male–specific mRNA was also detected in the lacrimal gland fibroblasts by in situ hybridization. The donor–origin of the fibroblasts was further confirmed by detecting the Y–chromosome sequence and the donor–specific microsatellite genetic markers in primary fibroblast cultures. Conclusions: The donor–derived fibroblasts are present in a chimeric state in the lacrimal gland of patients with chronic GVHD. Our findings strongly suggest that fibroblasts originated from circulating donor–derived precursors actively participate in the pathogenic process of lacrimal gland chronic GVHD.
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