The Infectious Disease and Immugenetics section of the Department of Transfusion Medicine is focused on the identification of genetic variables that may influence the outcome of immunization protocols against cancer and/or infectious agents and in general against diseases that are prodominantly controlled by cellular immune responses.? The Program includes two components: the Human Leukocyte Antigen (HLA) typing laboratory that is mainly covering the routing identification of known genetic variance among different populations through HLA molecular testing. In addition the HLA laboratory is going to more broadly apply immugenetic profiling that includes typing of other immune relevant genes such as Killer Cell Immunoglobulin Like Receptors (KIR), Cytokines and FC-Receptors.? The second component is the Immunogenetics Research Laboratory that includes a Fucntional Genomics Unit, a Proteomics Unit, a Single Nucleotide Polymorphism (SNP) detection unit, a pathogen chip detection unit and a T cell physiology unit. All of these units interact among them and with the HLA laboratory for the development of an integrated approach to the study of individual responses to immunological therapy aimed at the enhancemend of adaptive or innate immune responses with special emphasis on cellular immune responses.? Clinically, the Immunogenetics Program has developed in the last years a protocol for the assessemnt of immunogenetic variance across populations. The first one is aimead at the recruitment of 30 Caucasian and 30 Chinese donors that will be tested for their immune responses to antigen (i.e. latent memebrane protein-2 of the Epstein-Barr virus; LMP-2) or general pathogenic or therapeutic stimulation with lypopolysaccharide (LPS) or interleukin-2 (IL-2). Such responses were confronted with the genetic backgrounds of the two populations by comparing changes in global transcript and protein expression with different genetic profiles that could be identified using a newly developend high-throughput oligonucleotide SNP detection chip and well as a quantititive PCR, automated, high throughput sceening epitope mapping system.? The hypothesis is that different ethnic background may modulate the response to general immune stimulators or antigen-specific responses in relation to differences in the ability of various genes to respond to stimulation.? In addition, LMP-2 epitope mapping will be performed to see whether the notorioulsy different HLA phenotypes carried by the two populations will lead to differences in T cell responses to one of the immunogenic EBV proteins. ? This work will yield a global view of the possible influence that genetic background may have on disesase predisposition, outcome and response of therapy in the context of immune responses. In particular, it may explain differences in individual responses to T cell-aimed immunizations.? ? In addtion, a new project has been started in which the variance to response to intereferon alpha will be analyzed in normal individuals and in patients with melanoma or chronic hepatitis C. This project is aimed at identifying possible genetic traits that may be responsible for the variability of individual responses to therapy to this cytokine and other related biological products.? ? In conclusion the Immunogenetics Program of the DTM, CC is devoted at the development and implementation of Translational Medicine efforts for the study of the immune responses in individuals of different ethnic background to active-specific immunization agains cancer and other chronic conditions predominantly controlled by cellular immune responses.
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