Textbook of Personalized Medicine - Second Edition [2015]

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of treatment regimens may be benefi cial. A study using radioimmunoassays to
measure levels of anti-infl iximab antibody and of TNFα binding due to infl iximab
in rheumatoid arthritis patients has shown that development of anti-infl iximab anti-
bodies, heralded by low preinfusion serum infl iximab levels, is associated with
increased risk of infusion reaction and treatment failure (Bendtzen et al. 2006 ).
Early monitoring may help optimize dosing regimens for individual patients, dimin-
ish side effects, and prevent prolonged use of inadequate infl iximab therapy.


Personalized Therapy of RA Guided by Anti-citrullinated


Protein Antibodies


Although a large number of targeted therapies (TNF, IL6, CD80/CD86 and CD20
inhibitors) have become available to better treat the underlying disease process,
identifi cation of the underlying pathways that drive the disease process in an indi-
vidual patient has been relatively unsuccessful, implying that no predictive factors
have been identifi ed to guide the choice of a specifi c treatment. Distinct subsets of
RA patients have been identifi ed, based on the presence or absence of anti-
citrullinated protein antibodies (ACPAs). Two subsets are associated with different
environmental and genetic risk factors, histology and disease outcome. A more
destructive disease course with persistent joint infl ammation is observed when
ACPAs are present. Therefore, treatment should be aimed at a more consistently
low level of disease activity in the presence of ACPAs than in the absence of the
antibodies (Huizinga 2014 ).


Personalized Approaches to Improve Organ Transplantation


Matching in organ transplantation is already personalized. Management of compli-
cations, the most important of which is organ rejection, can be improved by per-
sonalized approaches. Two examples of typical organ transplants, kidneys and
heart, will be used to illustrate how personalized approaches can improve organ
transplantation results.


Personalization of Kidney Transplantation


Although tissue and blood matching is done prior to organ transplantation, there are
still problems of rejection after transplantation. Among transplant patients, 50 %
lose their kidneys within 8-10 years. With immunosuppressants, a transplanted kid-
ney can survive and function well for years. However, immunosuppressants also
have a dark side. Immunosuppressive drugs make transplant patients more likely to


17 Personalized Approaches to Immune Disorders
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