CCCardiol CroatCardiologia CroaticaCardiol. Croat.1848-543X1848-5448Croatian Cardiac SocietyCC_13(11-12)_37110.15836/ccar2018.371Extended AbstractAntibody-mediated rejection in heart transplant patients: a single centre experienceProtutijelima posredovano odbacivanje srčanog presatka: iskustvo jednog centrahttps://orcid.org/0000-0001-5979-2346SkorićBoško*https://orcid.org/0000-0003-2633-3439FabijanovićDorahttps://orcid.org/0000-0002-3197-2190PašalićMarijanhttps://orcid.org/0000-0001-7304-1127JakušNinahttps://orcid.org/0000-0003-0441-4772DubravčićMiahttps://orcid.org/0000-0002-4772-5549ČikešMajahttps://orcid.org/0000-0001-7171-2206Ljubas MačekJanahttps://orcid.org/0000-0002-9346-6402SamardžićJurehttps://orcid.org/0000-0002-2599-553XJurinHrvojehttps://orcid.org/0000-0003-0561-6704PlanincIvohttps://orcid.org/0000-0002-5052-6559LovrićDanielhttps://orcid.org/0000-0003-2607-3059ŽunecRenatahttps://orcid.org/0000-0003-2781-4576Burek KamenarićMarijahttps://orcid.org/0000-0003-1988-6684IlićIvanahttps://orcid.org/0000-0002-7282-9753IvančanVišnjahttps://orcid.org/0000-0002-2492-3702GašparovićHrvojehttps://orcid.org/0000-0003-3362-9596BiočinaBojanhttps://orcid.org/0000-0001-9101-1570MiličićDavorMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, HrvatskaUniversity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, CroatiaADDRESS FOR CORRESPONDENCE: Boško Skorić, Klinički bolnički centar Zagreb, Kišpatićeva 12, HR-10000 Zagreb, Croatia. / Phone: +385-95-3959-910 / E-mail: bskoric3@yahoo.com1120181311-1237137228102018051120182018Croatian Cardiac SocietyKLJUČNE RIJEČI: protutijelima-posredovano odbacivanjetransplantacija srcadonor-specifična protutijelaKEYWORDS: antibody-mediated rejectionheart transplantdonor-specific antibodies
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
LITERATUREColvinMMCookJLChangPFrancisGHsuDTKiernanMSAmerican Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiopulmonary Critical Care, Perioperative and Resuscitation; American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Disease in the Young; American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology, Council on Cardiovascular and Stroke Nursing; American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Radiology and Intervention; American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Surgery and Anesthesia. Antibody-mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management: a scientific statement from the American Heart Association. . 2015 May 5;131(18):1608–39. 10.1161/CIR.000000000000009325838326KobashigawaJColvinMPotenaLDragunDCrespo-LeiroMGDelgadoJFThe management of antibodies in heart transplantation: an ISHLT consensus document. . 2018 May;37(5):537–47. 10.1016/j.healun.2018.01.129129452978