Biology Reference
In-Depth Information
a healthy new genome into a patient to cure hematologic disorders. The
drastic biological perturbations caused depend on both the genetic make-
up of the donor and that of the recipient. Donor/recipient histocompatibil-
ity can be assessed by correlating biological and physiological effects, thus
identifying the genetic contribution of MHC alleles, haplotypes and their
combined effects. This opens up, for example, the possibility of neutralizing
MHC genetic differences by performing hematopoietic cell transplantation
between HLA identical siblings. Such a clinical setting makes it possible
to highlight the effects of other immunogenetic systems, such as minor
histocompatibility loci, cytokines, receptors, which currently may have a
more limited yet significant influence on the outcome of transplantation.
Among the major bottlenecks in translating systems biology into individ-
ualized systems medicine is the limited number of clinical cases that can
be included in randomized trials and the number of genetic and environ-
mental variables that cannot be easily accounted for. With the increasing
number of genetic systems and alleles that have to be taken into account,
the number of transplants available for investigation is a major limiting fac-
tor. Are virtual patient models that mimic the patients' main characteris-
tics, from which testable hypotheses can be generated and validated on the
small number of actual patients available, one solution? In the future, a sys-
tems biology approach and integrative methodologies will undoubtedly be
needed to unravel the role of immunogenetics in transplantation in order
to bring tailored and personalized treatment to the individual patient
[124]
.
33
Acknowledgments
We thank Dr Mari Malkki for assistance in preparation of the figure, Dr Wahid Boukouaci for
discussion and Nadia Meynard and Stuart Tenney for editing assistance. EWP is supported by
grants CA18029, CA100019, CA162194 and AI069197 from the National Institutes of Health.
DC is supported by grants EC “CARE-MI” and INSERM UMRS 940 “Hematology-Immunology-
Targeted Therapy”.
References
[1] Dausset J. Leuco-agglutinins IV: leuco-agglutinins and blood transfusion. Vox Sang
1954;4:190-8.
[2] van Rood JJ, van Leeuwen A. Leukocyte grouping. A method and its application. J Clin
Invest 1963;42:1382-90.
[3] Trowsdale J. HLA genomics in the third millennium (Review). Curr Opin Immunol
2005;17:498-504.
[4] Charron D. Immunogenetics today: HLA, MHC and much more. Curr Opin Immunol
2005;17:493-7.
[5] Traherne JA. Human MHC architecture and evolution: implications for disease associa-
tion studies. Int J Immunogenet 2008;35:179-92.
[6] Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC. Structure of
the human class I histocompatibility antigen, HLA-A2. Nature 1987;329:506-12.
[7] Marsh SG, Albert ED, Bodmer WF, Bontrop RE, Dupont B, Erlich HA, et al. Nomencla-
ture for factors of the HLA system 2004. Tissue Antigens 2005;65:301-69.
[8] IMGT/HLA Database.
http://www.ebi.ac.uk/imgt/hla
[9] Rammensee HG. Chemistry of peptides associated with MHC class I and class II
molecules (Review). Curr Opin Immunol 1995;7:85-96.
[10] Rodgers JR, Cook RG. MHC class Ib molecules bridge innate and acquired immuni-
ty. Nat Rev Immunol 2005;5:459-71.
[11] Ulbrecht M, Couturier A, Martinozzi S, Pla M, Srivastava R, Peterson PA, et al. Cell
surface expression of HLA-E: interaction with human beta
2
-microglobulin and allelic
differences. Eur J Immunol 1999;29:537-47.
Search WWH ::
Custom Search