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TEN YEAR OVERVIEW OF DEFINING A CHRONIC REJECTION-FREE STATE BY DONOR ANTIGHEN-SPECIFIC HYPOREACTIVITY.
Angela D. Burnette, B.S. , Karen Mohler B.S.,MT , Lois McHugh MS,RN , Arthur Matas M.D. , Kay Savik MS and Nancy L. Reinsmoen, Ph.D. . Durham NC, Duke University Medical Center, 27710, Pathology and Minneapolis MN, University of Minnesota, 55455, Department of Surgery .
Over the past 10 years we have identified donor antigen-specific responder status for over 550 solid organ recipients. Donor antigen-specific hyporeactivity (DASH), defined as a significant decreased [>60%] post- vs. pretransplant donor antigen-specific bulk culture mixed lymphocyte proliferative response to cells expressing donor antigen, was identified for 26% (108/422) of kidney (KD), 39% (16/41) of lung (LNG), and 54% (25/46) of heart tx recips (data not shown). In all three organ groups the hyporeactive subgroup experienced fewer late (>3 mo) acute rejection (AR) episodes and a lower incidence of chronic rejection (CR). The median time to CR for LNG recips who remained responsive to donor antigen was 15.4mo vs. 38.4mo for those who developed DASH. Although LNG recips have the highest rate of CR among tx organs, those who develop DASH remain CR-free for a longer period of time. An AR episode is the major risk factor in the development of biopsy-proven CR in KD recips. Of KD recips with a previous AR, 41% (62/153) developed CR while only 4% (11/250) of recips with no AR episodes developed CR. We investigated the impact of donor antigen-specific responder status and AR on the development of CR in KD recips. For KD recips with AR, a low rate of CR 26% (11/42) was observed for those who developed DASH, while a higher rate of CR 41% (45/111) was observed for KD recips who remained responsive to donor antigen. The odds of developing CR for the KD recip that remained responsive to donor antigen were 1.92 times more likely than those who developed DASH. Thus monitoring changes in donor antigen-specific responder status proved useful in identifying recips at low vs. high risk for CR.