Crypt loss, pericapillary hemorrhage, and severe gastrointestinal graft-versus-host disease
To the Editor: The very complete study of Melson et al. [1] demonstrates the value of crypt loss as a marker of severity in acute graft-versus-host disease (GVHD) in a series of colonic biopsies in twenty seven patients. Interestingly, the authors underline that ''crypt loss was not evident in the absence of accompanying apoptosis, confirming prior reports that the presence of crypt loss is specific of gastrointestinal GVHD and accompanies the presence of apoptosis''.
They also report that in the three patients of their series who underwent simultaneous biopsy of the colon and upper gastrointestinal tract, severe crypt loss was also present in the duodenum. This point is important because it indicates an extensive disease of the whole digestive tract. In a previous study of ninety five patients with upper gastrointestinal biopsies [2], we also found such an extensive GVHD of the whole digestive tract in the fourteen patients with concomitant duodenal and colonic biopsies. Moreover, we found that the number of apoptotic cells was significantly correlated with the severity of GVHD in this series.
In an experimental model of acute GVHD, we demonstrated that endothelial cells, as well as epithelial cells can be the target of the allogeneic reaction, and that both types of cells undergo apoptosis through the activation of the Fas/ FasL pathway [3]. In human, cutaneous endothelial cell damage was reported in chronic GVHD, with progressive loss of microvessels [4]. We also found endothelial cell apoptosis in duodenal biopsies of patients with acute GVHD, with resulting pericapillary hemorrhage, and this latter damage was significantly correlated with GVHD severity [5].
Taken together, these concordant results suggest that apoptosis of target cells, both epithelial, with crypt loss, and endothelial, with pericapillary hemorrhage, induces severe extensive damage in the digestive tract. Moreover, the loss of crypts, whose epithelium contain cells able to repair the upper part of the digestive epithelium, can also contribute to poor therapeutic response, by impairing the mechanism of digestive tract tissue repair.