Background
Graft-versus-Host Disease (GVHD) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT). Transplacental maternal engraftment (TME), the presence of maternal T cells in peripheral blood prior to transplant, is detectable in a significant proportion of SCID patients. While the presence of TME is associated with a decreased risk of rejecting a maternal graft, it is unknown whether TME plays a role in development of GVHD post HSCT.
Objective
The purpose of this study was to determine whether the presence of pre-transplant TME is associated with post-transplant GVHD in SCID patients.
Methods
This was an institutional retrospective review of 74 patients with SCID transplanted between 1988–2014. The incidence of acute GVHD was compared in patients with TME versus those without TME. Confounding variables such as donor type and conditioning regimen were included in a multivariate regression model.
Results
TME was identified in 35 of 74 children. Post-HSCT acute GVHD developed with an incidence of 57.1% vs 17.9% in those without TME (p<0.001). In univariate analysis, donor type (mother) and GVHD prophylaxis (T cell depletion) were also significant predictors of acute GVHD. In multivariate analysis, TME and chemotherapy conditioning were independent risk factors for the development of aGVHD (RR=2.75, p=0.006 and RR=1.42, p=0.02, respectively).
Conclusion
TME independently predicts the development of post-transplant aGVHD, even when controlling for donor type and conditioning used. The presence of TME should be considered when assessing the risk of aGVHD in SCID patients and designing the approach for GVHD prophylaxis.
Myxococcus xanthus is a Gram-negative, soil-dwelling bacterium that glides on surfaces, reversing direction approximately once every 6 min. Motility in M. xanthus is governed by the Che-like Frz pathway and the Ras-like Mgl pathway, which together cause the cell to oscillate back and forth. Previously, Igoshin et al. (2004) suggested that the cellular oscillations are caused by cyclic changes in concentration of active Frz proteins that govern motility. In this study, we present a computational model that integrates both the Frz and Mgl pathways, and whose downstream components can be read as motor activity governing cellular reversals. This model faithfully reproduces wildtype and mutant behaviors by simulating individual protein knockouts. In addition, the model can be used to examine the impact of contact stimuli on cellular reversals. The basic model construction relies on the presence of two nested feedback circuits, which prompted us to reexamine the behavior of M. xanthus cells. We performed experiments to test the model, and this cell analysis challenges previous assumptions of 30 to 60 min reversal periods in frzCD, frzF, frzE, and frzZ mutants. We demonstrate that this average reversal period is an artifact of the method employed to record reversal data, and that in the absence of signal from the Frz pathway, Mgl components can occasionally reverse the cell near wildtype periodicity, but frz- cells are otherwise in a long nonoscillating state.
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