Novel Antibodies to the Donor Stem Cell Population CD34+/VEGFR-2+ Are Associated With Rejection After Hematopoietic Stem Cell Transplantation

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Abstract
Background. Reconstitution of hematopoiesis after hematopoietic stem cell transplantation (HSCT) occurs through a reservoir of donor CD34+ HSC. CD34+/VEGFR-2+ is a primitive, quiescent subpopulation of HSC known to generate hematopoietic or endothelial progeny in vitro and in vivo. We hypothesized that donor-specific antibodies to the CD34+/VEGFR-2+ stem cells may be associated with rejection after HSCT. Methods. We studied 30 patients without and 11 with rejections after HSCT and 20 nontransplanted healthy individuals. Ninety-three sera taken pre and posttransplantation from patients receiving HSCT were studied for the presence of donor CD34+/VEGFR-2+ cell-specific antibodies. Results. We provide evidence that significantly higher numbers of patients with rejections 9/11 (81%), whereas 1/30 (3%) (P=0.001) without rejections had antibodies against donor CD34+/VEGFR-2+ cells, but not CD34−/VEGFR-2− cells. In eight transplantations, antibodies against donor CD34+/VEGFR-2+ cells were detected already before transplantation. Purified IgG fractions from patients with rejections but not controls significantly decreased the ability of these cells to form hematopoietic and endothelial colonies. In multivariate analysis, antibodies against CD34+/VEGFR-2+ cells proved to be the most significant risk factor for rejection. Conclusions. These novel findings document a high rate of rejections in patients with donor-specific antibodies to CD34+/VEGFR-2+ HSC. These antibodies may significantly and commonly contribute to HSCT rejections.

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