Men and women who receive donated organs can have
different rates of transplant rejection, in some
cases influenced by the sex of the donor.
A new study by investigators at Brigham and Women’s
Hospital assesses what is currently known about the
influence of biological sex differences, possible
mechanisms that may explain discrepancies between
rejection rates for male and female recipients and
what questions remain to be explored in future
In general, the influence of biological sex on
transplant outcomes has not been rigorously studied
and largely underappreciated.
“In solid organ transplantation, the importance and
implications of the sex of both the donor and the
recipient have long been underappreciated,” said
Stefan G. Tullius, MD, PhD, chief of the Division of
Transplant Surgery at BWH.
“The differences may be subtle but I think they are
very relevant, particularly as we move toward
individualizing immunosuppression and try to find
ways to be more specific in our treatment. I think
understanding the relevance of sex differences will
play a significant role in this.”
Transplant rejection is a complicated phenomenon
with many contributing factors, and the researchers
note that mismatched sex of a donor should not be
cause for concern for transplant recipients.
However, data on transplant rejection rates have
been correlated with specific patterns of donor and
recipient sex in several types of transplanted
organs, including kidneys and hearts.
In kidney transplantation, female donor sex has been
associated with an increased rate of transplant
organ rejection, especially among male recipients.
In cardiac transplantation, female donor organs have
also had lower rates of success compared to male
However, in contrast to kidney transplantation,
these differences are only consistently present in
male recipients and absent in female recipients.
The authors also note the importance of age – among
women 45 and older, they observed a positive effect
among female recipients, especially when they
received a transplant from a female donor.
Tullius and his colleagues describe two important
categories of molecular sex differences that may
influence immune response and help account for these
different rates: genetics and hormones.
Approximately 50 genes on the X chromosome have
immunological functions, and may be more variably
expressed in females.
The Y chromosome, on the other hand, harbors genetic
loci for male-specific antigens.
Different hormonal environments in males and females
may influence multiple immune cell types that
express hormone receptors.
The team also notes that certain therapies that
target hormone receptors – such as selective
estrogen receptor modulators – could be used in the
future to target these hormonally-mediated
differences between male and female immune
Further analysis in experimental and clinical models
will be needed to determine if this kind of
therapeutic approach may be helpful for organ
For more information
Trends in Immunology
The Impact of Sex on Alloimmunity