Antibody-Mediated Rejection

SECTIONS Introduction (Manuel Arias) De novo Donor-Specific HLA Antibodies in Renal Transplantation: A Major Cause of Graft Loss (David N. Rush, Chris Wiebe, Ian W. Gibson, Tom D. Blydt-Hansen, and Peter W. Nickerson) Causes of Late Kidney Allograft Loss. What’s New? (Joana Sellarés) Epidemiology of Anti-HLA Antibodies in Solid Organ Transplantation: Impact of New Solid-Phase Tests (Marcos López Hoyos, David San Segundo, and Manuel Arias) The Definition and Diagnosis of Antibody-Mediated Rejection in Heart Transplantation (María G. Crespo-Leiro, Raquel Marzoa-Rivas, Eduardo Barge-Caballero, and María J. Paniagua-Martín) Antibody-Mediated Rejection in Lung Transplant. What Is Changing? (Antonio Román) Inflammation, Fibrosis, and Immunosuppressive Treatment (Daniel Serón) Prevention and Treatment of Alloantibody-Mediated Transplant Rejection: New Approaches (Elisabeth Schwaiger and Georg A. Böhmig) 1. INTRODUCTION Manuel Arias Overall graft survival has increased progressively over the last years. According to national and international registries, such as the Collaborative Transplant Study (CTS), graft loss has followed a downward trend (1, 2) (Fig. 1).FIGURE 1: Evolution of graft survival over the last years according to the CTS (1).The introduction of new immunosuppressive (IS) drugs—together with a better understanding of rejection physiopathology in solid organ transplantation—have globally improved short-term outcomes with reduced rates of acute rejection. However, late graft failure is still an issue (2). The risk of graft failure includes immunological and nonimmunological factors (3) (Table 1). Considering the immune factors, the incidence of antibody-mediated rejection (AMR) has increased over the last years: partly caused by a higher number of retransplantation and transplants with human leukocyte antigens (HLA) and ABO incompatibility, and partly because of a greater recognition of this entity and the availability of improved tests to detect donor-specific antibodies (DSA) (4).TABLE 1: Risk factors and reported causes of graft failureThere is a temporary dynamic in the course of chronic humoral rejection (CHR). Based on histological findings, renal allograft damage starts with tubule-interstitial inflammation followed by a later phase of chronic allograft nephropathy defined by arteriolar hyalinosis and glomerulosclerosis. The presence of interstitial inflammation in early protocol biopsies (performed within 6 months after transplantation) is related to a higher risk of developing de novo DSA (dnDSA) and consequently CHR. Therefore, the benefit of treating subclinical rejection must be considered while taking into account that the IS regimen can influence the outcome. Thus, the renal damage attributed to calcineurin inhibitors (CNI) toxicity, leading to a minimization of these drugs, has resulted in greater increases of chronic pathology. The availability of new solid-phase assays (SPA), allowing the detection of low titers of DSA, has revealed the importance of these antibodies in the development of AMR and the related risk of graft failure, regardless of the solid organ transplanted. New SPA also point out the importance of considering and such as in the of DSA be a in such as with and humoral rejection is considering an IS Considering the of the a and the presence of into account the such as IS with HLA and minimization and to IS is a risk the development of is considered a of renal graft a of chronic antibody-mediated rejection is to on risk of the subclinical of to graft the DSA in to such as Therefore, and early of considering histological and findings, of importance in the and of this the and on of antibodies and on of of the be the has in the after the and is still a of developing AMR is an issue solid organ in this the the and the in the Antibody-Mediated Rejection: the in in HLA A David N. Rush, Chris Wiebe, Ian W. Gibson, Tom D. Blydt-Hansen, and Peter W. 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