August 16, 2012
Detailed below is the fifth and final achievement the Immune Tolerance Network (ITN) recently presented at the Member Society Symposium at the Federation of Clinical Immunology Societies (FOCiS) meeting, and how this work fits in with the broader pursuit of tolerance in transplantation.
Clinical experiences have suggested a number of mechanisms that may contribute to tolerance in solid organ transplantation, including immune ignorance, clonal exhaustion, anergy, regulation and deletion of donor-reactive cells. Defining signatures and mechanisms of tolerance will be important for identifying patients that can be safely weaned from immunosuppression, and for refining tolerogenic induction and treatment strategies. Ken Newell, MD, PhD (Emory University) presented the findings from the ITN’s FACTOR Study of Tolerant Kidney Transplant Recipients, which identified a B-cell-specific signature associated with tolerance. Other kidney transplant signature studies have similarly found B cell-related genes associated with tolerance. Similar immunosuppressive therapies in other solid organ transplantation yields a different signature, supporting the B cell signature as being one of tolerance in kidney transplantation rather than a drug effect. The transitional B cells that are the hallmark of the signature express higher levels of IL-10, supporting the notion that regulatory B cells may be functionally involved in the tolerance phenotype. Further research is needed, however, to validate the signature’s use as a predictive biomarker.
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