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2014 ASTS Vanguard Prize Recipients

Raymond J. Lynch

Raymond J. Lynch, MD, MS
Emory University

Synopsis: Solid organ transplant is widely recognized as one of the most provocative stimuli for the immune system. Despite this, most recipients of renal grafts do not have measurable titers of alloantibody in the initial period following transplantation. Possible explanations for this discrepancy include either a delayed or absent immune response, or an intact response with some other mechanism clearing circulating antibody. To differentiate between these possibilities, we designed an assay to measure allospecific circulating B cells of healthy kidney recipients. We found that these cells do increase in number, indicating that modern immunosuppression does not abrogate B cell activation in the absence of rejection. This in turn suggests that other, as yet undescribed, factors modify or ameliorate immune responses in transplant recipients.

Shunji Nagai

Shunji Nagai, MD, PhD
Indiana University

Synopsis: Lymphocytes play an active role in natural immunity against hepatitis C virus (HCV). We hypothesized that a lower absolute lymphocyte count (ALC) may alter HCV outcome after liver transplantation (LT). In this study, peritransplant ALC (pre-LT, 2-week, and 1-month post-LT) and immunosuppression were analyzed along with recipient and donor factors in order to determine risk factors for HCV recurrence in 289 patients. When stratifying patients according to pre- and post-LT ALC (<500/μL versus 500-1,000/μL versus >1,000/μL), lymphopenia was significantly associated with higher rates of HCV recurrence with fibrosis (F2-4). When peritransplant ALC was persistently low (<500/μL pre-LT, 2-week, and 1-month post-LT), patients were at significant risk of developing early advanced fibrosis secondary to HCV recurrence (F3-4 within 2 years). The use of rabbit anti-thymocyte globulin induction had a remarkable protective effect on HCV recurrence despite its potential to induce lymphopenia. Peritransplant ALC is a novel and useful surrogate marker for prediction of HCV recurrence and patient survival. Immunosuppression protocols and peritransplant management should be scrutinized depending on peritransplant ALC.