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Alloimmunization and Tolerance

 

Using a combination of clinical samples and transfusion models, we are evaluating mechanisms regulating alloimmunization, clinical outcomes such as platelet refractoriness, and methods for preventing alloimmune responses to current and future exposures through tolerance induction. One promising approach is through the use of pathogen reduction technologies (PRT). We have found that a riboflavin and UV-light-based PRT, designed to reduce the risk of transfusion-transmission of infectious disease, has an added benefit of protecting against alloimmunization. In addition to blocking the primary response to allogeneic white blood cells, transfusion with pathogen reduced blood appears to down-modulate immune responses to future allogeneic exposures in an antigen-specific manner. We are now working to uncover the mechanisms regulating this protective effect, with the long-term goal of manipulating this response to protect recipients of blood transfusions and transplants.

 

Selected Publications:

 

Jackman R.P., Heitman J.W., Marschner S., Goodrich R.P., Norris P.J. (2009).  “Understanding loss of donor white blood cell immunogenicity after pathogen reduction: mechanisms of action in ultraviolet illumination and riboflavin treatment.” Transfusion 49(12):2686-99. PMC2865145.

 

Jackman R.P., Deng, X., Bolgiano, D., Lebedeva, M., Heitman, J.W., Busch, M.P., Slichter, S., Norris P.J. (2013). “Low-level HLA antibodies do not predict platelet transfusion failure in TRAP study participants.” Blood 121(16):3261-3266. PMC3630837.

 

Jackman R.P., Muench, M.O., Heitman, J.H., Law, J.P., Inglis, H., Marschner S., Goodrich R.P., Norris P.J. (2013).  “Immune Modulation and Lack of Alloimmunization Following Transfusion with Pathogen Reduced Platelets in Mice.” Transfusion. 53(11): 2697-709.  PMID: 23451715

 

Jackman R.P., Deng X., Bolgiano D., Utter G.H., Schechterly C., Lebedeva M., Operskalski E., Luban N.L., Alter H., Busch M.P., Slichter S.J., Norris P.J. (2014). “Leukoreduction and ultraviolet treatment reduce both the magnitude and the duration of the HLA antibody response.” Transfusion 54(3):672-80. PMC3825847.

 

Jackman, R.P., Lee, J-H., Pei, R., Bolgiano, D., Lebedeva, M., Slichter, S., Norris P.J. (2016). “C1q-binding anti-HLA antibodies do not predict platelet transfusion failure in TRAP study participants.” Transfusion, 56(6):1442-1450. PMID: 27079754

 

Muench, M.O., Heitman, J.H., Inglis, H., Fomin, M.E., Marschner S., Goodrich R.P., Norris P.J., Jackman R.P. (2016).  “Reduced Alloimmunization in Mice Following Repeated Transfusion with Pathogen Reduced Platelets.” Transfusion, 56(6):1419-1429. PMID: 27028210

 

Jackman, R.P., Muench, M.O., Inglis, H., Heitman, J.H., Marschner S., Goodrich R.P., Norris P.J. (2016). “Reduced MHC Alloimmunization and Partial Tolerance Protection With Pathogen Reduction Of Whole Blood.” Transfusion, In Press.