ABSTRACT
I. Introduction The presence of antibodies to human leukocyte antigen (HLA) in the blood of a potential solid organ transplant recipient places such a patient at risk for the development of hyperacute allograft rejection. A “sensitized” patient was initially described in kidney transplantation in the 1960s, and subsequently, HLA antibodies have been associated with antibody-mediated allograft rejection (AMR) and poor outcomes (1). The first published account of hyperacute rejection following lung transplantation was described by Frost and colleagues in 1996 when pretransplant crossmatching was not routine (2). Close attention to panel reactive antibody (PRA) testing and prospective crossmatching of potential lung donor lymphocytes with recipient serum has virtually eliminated this event. The awareness of this circumstance and the development of improved techniques to detect and identify the specificities of anti-HLA antibodies have lead to the implication of donor-specific antibody (DSA) involvement in acute and chronic AMR (3). While evidence for AMR is strong in kidney and heart transplantation, only recently have publications in lung transplantation supported an association of anti-HLA antibodies with recurrent acute rejection (4), bronchiolitis obliterans syndrome (BOS) (5), and poor post-transplant survival (6,7). Between 10% and 17% of lung transplant recipients are presensitized to HLA antigens (7,8). Risk factors for sensitization include prior blood product transfusion, pregnancy, and previous organ transplant. ABO blood type and donor size are the primary considerations when accepting a potential organ allograft. However, patients with a positive PRA traditionally require a prospective crossmatch between donor lymphocytes and recipient serum. Allograft ischemic limitations and the inherent delay due to the crossmatch procedure place these patients at a disadvantage by limiting the donor pool to the local area. Newer more sensitive techniques used for the detection of anti-HLA antibody specificities have allowed the expansion of available donors to outside zones by matching donor HLA type and recipient serum anti-HLA antibody specificities (virtual crossmatch) (9). Despite the virtual crossmatch, patients with high PRA levels (>25%) still find it difficult to find an appropriate donor match. Desensitization techniques using IV immunoglobulin (IVIg), plasmapheresis, and medications to suppress the T-and/or B-cell response (mycophenolate mofetil, rituximab) have been successfully utilized to reduce anti-HLA antibodies both before and
after transplantation (10). Herein, a description of the approach to the sensitized lung transplant recipient is discussed.
