CLINICAL NEWS
High Expression of HLA-DPB1 Mismatching
Increases Risk of Graft-Versus-Host Disease
and Death
Though hematopoietic stem cell transplantation (HSCT) from unrelated donors can cure
some blood disorders, an HLA-mismatched
transplantation can result in graft-versus-host
disease (GVHD) which, if severe, can adversely
affect outcome. The risk of GVHD is higher
when the recipient and donor are HLA-DPB1mismatched, though the mechanism of GVHD
remains unknown.
In a study published in The New England
Journal of Medicine, Effie W. Petersdorf,
MD, from Fred Hutchinson Cancer Research
Center in Seattle, Washington, and colleagues
conducted a genotyping study to examine the
GVHD risk associated with the rs9277534
allele, which is related to HLA-DPB1 expression, and how it is linked to the mismatched
HLA-DPB1 in the transplant recipient.
“We now understand the machinery in
our genome that governs protein expression
actually has biological significance that is
important to patients,” Dr. Petersdorf said in a
press release from Fred Hutchinson. “We have
not considered variation in the regions of genes
that are responsible for protein expression; up
until now, we have been focused on the specific
sequence of the protein itself.”
Dr. Petersdorf and colleagues analyzed transplantations in which only a single DPB1 allele
differed in the patient and the donor and the second DPB1 allele was shared. They hypothesized
that rs9277534G-linked HLA-DPB1 in a transplant recipient that is not shared by the donor
cells (constituting high-expression graft-versushost mismatch) is more visible to the donor cells
than the rs9277534A-linked HLA-DPB1 allele,
thus leading to a higher risk of acute GVHD.
“If the level of HLA-DPB1 expression provides
information about HLA-DPB1 mismatches that
are well-tolerated (i.e., associated with favorable
outcomes),” the authors wrote, “then rs9277534
TABLE 2.
can be used prospectively to screen potential
unrelated donors before transplantation in order
to lower the risk of acute GVHD.”
rs9277534 was genotyped in 3,505 patients
t