The ability to detect B cells specific to the DEAD box protein (DBY-2) may help predict the development of chronic graft-versus-host disease (cGVHD) in male recipients of female hematopoietic cells, according to recent findings.
"These findings may provide a mechanistic explanation for the moderate efficacy of in vivo B-cell depletion in treating cGVHD, and further suggests that more focused B-cell targeting, e.g., with DBY-2… might be more effective cGVHD therapy," write Leonard Herzenberg and David Miklos and colleagues, from Stanford University School of Medicine in California, USA, in the Proceedings of the National Academy of Sciences.
In a related press statement, Miklos said that "the overwhelming majority of patients who have these [DBY-2-specific] cells in their blood either have or will develop cGVHD within one to three months," and that previously there had been no reliable predictive indicators for cGVHD onset.
The investigators analyzed blood samples from 28 male patients with leukemia or lymphoma who received hematopoietic cell transplantation (HCT) grafts from female donors. The analysis took place 6 months after HCT.
Of the 28 patients, 16 (57%) had blood samples containing detectable DBY-2-specific B cells. Fifteen of the 16 patients eventually developed cGVHD, though six of those patients already had cGVHD when their blood was drawn. By contrast, only five of 12 patients who did not have DBY-2-specific B cells developed cGVHD.
Therefore, as the authors state, "we conclude that the presence of B cells with receptors that recognize the DBY-2 is positively associated with development of cGVHD." However, they acknowledge that the exact role these cells play in cGVHD is unclear; they may actively affect early pathogenesis or be passively induced by other T-cell-activating mechanisms.
The investigators recommend prospective monitoring of DBY-2-specific B cells in order to develop a more effective schedule for alloreactive B-cell depletion therapy, ultimately leading toward prevention of cGVHD. This monitoring will also allow for determining whether current depletion therapy is effective or if in fact these cells persist during cGVHD recurrence.
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