In addition, concurrent development of DSA and ACR as well as DSA and CLAD suggests a potential link between humoral and cellular immune responses
In addition, concurrent development of DSA and ACR as well as DSA and CLAD suggests a potential link between humoral and cellular immune responses. reactive antibody (CPRA), and the number of pre-transplant HLA antibodies were not associated with the development of acute cellular rejection, lymphocytic bronchiolitis, donor-specific HLA antibodies, chronic lung allograft dysfunction, or graft failure. == Conclusions == We conclude that pre-transplant allosensitization does not adversely impact outcomes after lung transplantation when the potentially reactive HLA are avoided in the donor by a virtual crossmatch with the recipient. Keywords:lung transplantation, allosensitization, panel reactive antibody == INTRODUCTION == Lung transplantation is the greatest treatment option for patients with end-stage lung disease. However, BRL-54443 long-term survival after transplantation remains disappointing, and the leading cause of death is usually chronic lung allograft dysfunction (CLAD) (1). Multiple studies have identified the development of donor-specific human leukocyte antigen BRL-54443 (HLA) antibodies (DSA) after transplantation as an important risk factor for the development of CLAD, lymphocytic bronchiolitis (LB), acute cellular rejection (ACR), antibody-mediated rejection (AMR), and death (29). However, the impact of pre-transplant HLA antibodies, or allosensitization, on post-transplant outcomes is less obvious, and previous studies have generated conflicting results. An early study using the complement-dependent cytotoxicity (CDC) assay concluded that pre-transplant allosensitization was uncommon, and a modestly elevated panel reactive antibody EIF4G1 (PRA) was not a risk factor for BRL-54443 CLAD, ACR, or death (11). In contrast, another study showed that patients who experienced a PRA > 10% required prolonged mechanical ventilation immediately after transplantation, were more likely to develop CLAD, and experienced a pattern to worse survival (12). A subsequent multicenter study using the CDC assay showed that recipients with a PRA > 25% were more likely to have a positive crossmatch and experienced a higher risk of death in the early post-transplant period (13). The increased morbidity and mortality associated with allosensitization after transplantation suggests that recipients may have had pre-existing DSA that were not detected by the CDC assay, ultimately resulting BRL-54443 in HLA-incompatible transplants. An analysis of the United Network for Organ Sharing (UNOS) registry found that a PRA > 25% was an independent risk factor for death after transplantation between 1987 and 1997, but not between 1998 and 2005 (14). The authors proposed that developments in HLA antibody detection methods improved donor selection and minimized the effects of allosensitization on post-transplant outcomes in the more recent era. Indeed, antibody analysis using solid-phase multiplex methods has allowed precise identification of antibody specificity, and potential donors with unacceptable HLA that would be expected to result in a positive direct crossmatch can then be avoided. Use of this virtual crossmatch can expand the donor pool and improve waitlist outcomes (15). The impact of pre-transplant allosensitization on long-term outcomes after transplantation in the era of solid-phase multiplex HLA antibody detection assays and virtual crossmatching has not been evaluated. We hypothesized that virtual crossmatching based on sensitive and specific HLA antibody detection assays would ameliorate the impact of pre-transplant allosensitization on post-transplant outcomes. == METHODS == == Study design == We conducted a retrospective cohort study including all patients outlined for lung transplantation at our program between 1/1/2006 and 12/31/2011. During this time period, 368 patients were outlined for transplantation; 3 were subsequently transplanted at another program and were excluded. Of the remaining 365 patients, 304 were transplanted at our center before 12/31/2012 and comprise this cohort. The remaining 61 patients died around the waitlist, were removed from the waitlist before transplantation, or were BRL-54443 still waiting on 12/31/2012. We conducted a separate study examining the impact of pre-transplant allosensitization on waitlist outcomes, and those results are not presented here (16). Our institutional review table approved this study as part of our lung transplant registry protocol. == Clinical management == At listing, we screened all patients for pre-formed HLA antibodies using the LABScreen Single Antigen assay. Thereafter, we repeated antibody screening every 3 months while on the waitlist and 24 weeks after a potentially allosensitizing event. Our centers histocompatibility lab defines HLA antibody positivity as reactivity with a mean fluorescence intensity (MFI) 2000. We used this cut-off for antibody detection before and after transplantation, and computed the calculated PRA (CPRA) using the UNOS calculator (17). We defined.