Antibody-mediated rejection in heart transplant patients: a single centre experience

    Authors

    Keywords

    antibody-mediated rejection, heart transplant, donor-specific antibodies

    DOI

    https://doi.org/10.15836/ccar2018.371

    Full Text

    The diagnosis of antibody-mediated rejection (AMR) is based on immunopathologic features, supported by clinical signs as well as by the presence of donor-specific antibodies (DSA). However, AMR is a continuum with progression from a silent phase of circulating antibodies, followed by subclinical complement deposition without histological alterations, until it becomes symptomatic. Subclinical AMR appears to be associated with poor outcome. DSA are markers of alloimmune activation and are associated with poor graft survival, rejection, and CAV (cardiac allograft vasculopathy). The significance of rising DSA in the early post-transplantation period, as well as their late appearance or increase without pathological changes or clinical manifestations, is unclear, and the treatment may be considered. ( 1 , 2 ) We retrospectively evaluated 193 transplant (Tx) patients (pts) since 2012, when pathologic analysis for AMR and detection of DSA were gradually introduced. By using different combinations of pathologic, clinical and serologic (i.e. positive DSA) criteria we diagnosed AMR in 12 pts (6.2%). One-quarter of patients with AMR presented with cardiogenic shock. The combination of pathologic and clinical, pathologic and serologic as well as clinical and serologic criteria were present in 17%, 25%, and 25%, respectively. All three criteria were positive in 33%. Median time from Tx to AMR diagnosis was 2.63 yrs (0.7-5.9). The median age was 35 (17-62) and 75% were males. All pts had positive DSA, except 2 pts, in whom testing was unavailable. Seventy percent had class II, and 30% were positive for both class I and class II anti-HLA. The most frequent treatment strategies included: pulse steroid (92%), plasma exchange (75%), intravenous immunoglobulin (58%) and rituximab (58%). Antithymocite globulin, as well as bortezomib, were applied in only one pts. ECMO was implanted in pts with cardiogenic shock. One-year survival is 83%. Among 193 pts, DSA were analyzed in 97 pts. Twenty-four percent were DSA positive (class I in 17%, class II in 65% and both classes in 17%) ( Figure 1 ). Although the reported incidence of AMR varies because of different diagnostic criteria and variations in screening schedule, our result is comparable. Both diagnosis and treatment of AMR are not well standardized. We need large prospective multicentric clinical trials to evaluate different strategies. The frequency of donor-specific HLA antibodies among tested heart transplant patients. HLA = human leukocyte antigen

    Cardiologia Croatica
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    Antibody-mediated rejection in heart transplant patients: a single centre experience

    Extended Abstract
    Issue11-12
    Published
    Pages371-372
    PDF via DOIhttps://doi.org/10.15836/ccar2018.371
    antibody-mediated rejection
    heart transplant
    donor-specific antibodies

    Authors

    Boško Skorić*ORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Dora FabijanovićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Marijan PašalićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Nina JakušORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Mia DubravčićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Maja ČikešORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Jana Ljubas MačekORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Jure SamardžićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Hrvoje JurinORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Ivo PlanincORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Daniel LovrićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Renata ŽunecORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Marija Burek KamenarićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Ivana IlićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Višnja IvančanORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Hrvoje GašparovićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Bojan BiočinaORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Davor MiličićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia

    Full Text

    The diagnosis of antibody-mediated rejection (AMR) is based on immunopathologic features, supported by clinical signs as well as by the presence of donor-specific antibodies (DSA). However, AMR is a continuum with progression from a silent phase of circulating antibodies, followed by subclinical complement deposition without histological alterations, until it becomes symptomatic. Subclinical AMR appears to be associated with poor outcome. DSA are markers of alloimmune activation and are associated with poor graft survival, rejection, and CAV (cardiac allograft vasculopathy). The significance of rising DSA in the early post-transplantation period, as well as their late appearance or increase without pathological changes or clinical manifestations, is unclear, and the treatment may be considered. ( 1 , 2 ) We retrospectively evaluated 193 transplant (Tx) patients (pts) since 2012, when pathologic analysis for AMR and detection of DSA were gradually introduced. By using different combinations of pathologic, clinical and serologic (i.e. positive DSA) criteria we diagnosed AMR in 12 pts (6.2%). One-quarter of patients with AMR presented with cardiogenic shock. The combination of pathologic and clinical, pathologic and serologic as well as clinical and serologic criteria were present in 17%, 25%, and 25%, respectively. All three criteria were positive in 33%. Median time from Tx to AMR diagnosis was 2.63 yrs (0.7-5.9). The median age was 35 (17-62) and 75% were males. All pts had positive DSA, except 2 pts, in whom testing was unavailable. Seventy percent had class II, and 30% were positive for both class I and class II anti-HLA. The most frequent treatment strategies included: pulse steroid (92%), plasma exchange (75%), intravenous immunoglobulin (58%) and rituximab (58%). Antithymocite globulin, as well as bortezomib, were applied in only one pts. ECMO was implanted in pts with cardiogenic shock. One-year survival is 83%. Among 193 pts, DSA were analyzed in 97 pts. Twenty-four percent were DSA positive (class I in 17%, class II in 65% and both classes in 17%) ( Figure 1 ). Although the reported incidence of AMR varies because of different diagnostic criteria and variations in screening schedule, our result is comparable. Both diagnosis and treatment of AMR are not well standardized. We need large prospective multicentric clinical trials to evaluate different strategies. The frequency of donor-specific HLA antibodies among tested heart transplant patients. HLA = human leukocyte antigen