The Development and Impact of De Novo Circulating Antibodies in Non-Sensitized Patients after Heart Transplantation

Abstract

Purpose According to the 2012 ISHLT Registry, two-thirds of patients at the time of transplant do not have circulating antibodies. For these non-sensitized patients, the incidence of post-transplant de novo antibody production has not been firmly established. Its impact on outcome in patients on routine triple drug immunosuppression has also not been determined. Methods and Materials Between 2006 and 2011, we evaluated 133 non-sensitized heart transplant patients for the development of de novo circulating antibodies [both non-specific and donor-specific antibodies (DSA)] in the first year after transplant. Blood for detection of circulating antibodies are routinely drawn at 1,3,6,12 months after heart transplant. Post-transplant outcomes assessed included 3-year survival, freedom from cardiac allograft vasculopathy (CAV), 1-year treated cellular rejection (CR) and antibody-mediated rejection (AMR). Results Of the 133 non-sensitized heart transplant patients, the development of non-specific antibodies was detected in 29 (22%) patients, DSA in 10 (7.5%) patients and no antibodies in 94 (70.5%) patients. Patients with first-year DSA had significantly lower survival and a trend for less freedom from CAV. The DSA and non-specific antibody groups had less freedom from first-year treated AMR (see table). Conclusions Non-sensitized pre-transplant patients who developed first year DSA after transplant have poor outcome. Treatment of these patients with anti-humoral therapies appears warranted, but merits a randomized trial. Outcomes No Ab (n=94) Non-Specific Ab (n=29) DSA (n=10) Log-Rank p-value 3-Year Actuarial Survival 93% 93% 50% 3-Year Freedom from CAV 84% 96% 70% 0.076 1-Year Freedom from Any-Treated CR 92% 90% 90% 0.970 1-Year Freedom from Any-Treated AMR 100% 90% 90% 0.007