JOURNAL CLUB
individuals compared with unrelated individuals. The hypothe-
sis went as follows: if there were a greater degree of GVHD
after transplants from unrelated individuals, then this attack of
the graft on the host might contribute to a more rapid disap-
pearance of host ABO antibodies after transplantation.
To investigate this, the authors retrospectively reviewed
ABO titer information on ABO-mismatched transplants. They
reviewed 383 major or major/minor ABO mismatched cases. Of
these, 155 had HLA-matched related donors, and 228 had
HLA-matched unrelated donors. The median time to reach
undetectable ABO titers of host origin was significantly shorter
among recipients from unrelated donors compared with related
donors (46 vs 61 days, P = .016). This suggested that the
GVHD found more commonly in unrelated transplants might
contribute to knockout of the host antibody production.
In addition, they examined titer information from 77 recipi-
ents of related-donor grafts who had clinical acute GVHD.
These patients had a 2.2-fold increased likelihood of reaching
undetectable titers by 100 days compared with 78 recipients of
related-donor grafts who did not have clinical GVHD.
The article carries some additional information of interest to
Transfusion Medicine Reviews readers. The authors examined
the effect of plasma exchange therapy on reaching the goal of
disappearance of host titers against the graft. In both unrelated-
and related-donor recipients, plasma exchange significantly de-
creased the likelihood of reaching low titer endpoints. Thus,
although plasma exchange could transiently lower antibody
titers, it did so without long-tasting beneficial effects presum-
ably because of production of new antibodies by the recipient.
The fact that plasma exchange patients did worse than those
without plasma exchange is likely because of selection bias
because patients with the highest titers of ABO antibodies
would be referred for plasma exchange.
The authors believed that tire findings obtained from simple
ABO titers supported the notion that among nonidentical allo-
grafts there is a graft-versus-plasma cell effect that contributes
to the elimination of the host humoral machinery. (S.D.)
Glycosylation and the immune system. P.M. Rudd, T.
E//iott, P. Cresswe//, et a/. Science 291 ;2370-2376, 2001.
All readers of Transfusion Medicine Reviews' Journal Club
will agree that polymorphisms of glycosylated proteins have a
profound importance in the immune system. Although carbo-
hydrate polymorphisms that determine ABO have been well
recognized for decades, recent investigations have found that
protein glycosylation plays a fundamental role in many immune
processes. These issues are very nicely summarized in this
special review of glycobiology in Science.
The authors describe the role of glyco-conjugates in the
folding, quality control, and assembly of peptide-loaded struc-
tures of the major histocompatibility complex (MHC). During
transport of glycoproteins through cytoplasmic pathways on
route to the cell surface, sugar chains undergo precise modifi-
cations that add to control of the transport and export of the final
secreted or membrane-bound glycoprotein. Examples include
the assembly and display of both class I and class II MHC
proteins.
They make the point that for glycosylated structures to be
deposited in the MHC groove, external glyco-conjugates must
first be removed by glycosylases. Indeed, the relative efficiency
323
(or lack thereof) at removing particular glyco-conjugates may
play an important role in the immune response to foreign
antigens and in the prevention of self-recognition and autoim-
munity.
Oligosaccharides clearly play an important role in the 3-di-
mensional orientation of folded proteins and in tile ability of
protein ligands to draw physically close to their receptors. The
authors use the model of the antigen-presenting ceils and T cells
as an example of this important function.
In the humoral system, glycosylation of immunoglobulins is
essential to their survival in. the circulation. Moreover, absence
of adequate glycosylation can result in increased aggregation of
immunoglobulins with resulting complement activation an im-
munopathology.
Finally, the presence of naturally occurring antibodies to
specific galactosyl residues represents an important xenotrans-
plantation barrier in higher primates including humans. There is
little doubt that glycobiology cuts across all aspects of the
immune system and a more refined understanding of the spe-
cific role of various glyco-conjugate species will be essential for
the immune manipulations of the next decade. (S.D.)
Leukocyte-reduced red blood cell transfusions in pa-
tients with anemia and human immunodeficiency vi-
rus infection: The viral activation transfusion study: A
randomized controlled trial. A.C. Co~tier, /.A. Ka/ish,
M.P. Busch, et al. JAMA 285:1592-1601, 2001.
In 1992, when high-performance leukocyte reduction was an
emerging technology, Mike Busch published a paper in Blood
showing that leukocytes latently infected with HIV virus could
be induced to undergo viral reactivation and active viral repli-
cation if co-cultured in vitro with noninfected allogeneic leu-
kocytes. This viral activation did not occur in response to
co-culture with red cells, with platelets, or with plasma. The
finding of that in vitro study led to widespread speculation that
HIV-infected individuals, if transfused with blood containing
donor leukocytes, would undergo viral activation and further
speculation that the transfusion of leukoreduced blood would
prevent such activation. Moreover, even less well-designed in
vitro studies were presented as possible evidence that the same
benefits might accrue for the prevention of activation of CMV.
Before tong, the prevention of viral activation was rather firmly
added to the list of speculative advantages of leukoreduced
blood components. Because viral activation of latent CMV
infection could affect large numbers of transfusion recipients,
prevention of viral activation became one of the foundation
indications for universal leukoreduction.
To address these concerns, the NIH sponsored the viral
activation transfusion study. Now, almost a decade after the
original in vitro studies the viral activation transfusion study
results have come to publication. The goal of the study was to
compare the effects of leukoreduced (LR) transfusions versus
unmodified transfusions on patient survival and on markers of
HIV infection. The study enrolled patients for 4 years and
involved 11 major medical centers in the United States. A total
of 531 patients infected with HIV and CMV were randomized
to the 2 study arms. Patients received a median follow-up of 1
year. Laboratory measures included plasma levels of HIV RNA
and CMV DNA before and 7 days after transfusion.
The results showed no benefit from leukoreduction. Regard-