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 other antibody specificities apart from HLA-A, -B and -DR, such as -Cw, -DQ or -DP, in the management of kidney transplantation. Moreover, DSA monitoring could be a useful tool in specific situations, such as desensitization protocols, patients with pretransplant antibodies, and negative complement-dependent cytotoxicity (CDC), when humoral rejection is suspected or when considering an IS therapy. Considering the role of the IS, whereas some authors demonstrated a clear relationship between treatment compliance and the presence of dnDSA, others took into account the physician’s decisions such as IS change or reduction (5). Together with Class II HLA mismatching and prior cellular rejection, inadequate immunosuppression (particularly minimization and nonadherence to IS medications) is a risk factor for the development of dnDSA, which is considered a major cause of renal graft loss. While waiting for a treatment of chronic antibody-mediated rejection is to on for or risk of the subclinical of from to graft the for DSA in patients to such as Therefore, and early of considering histological and findings, of importance in the and treatment of this the desensitization and on of antibodies and on of of the be for the has in the after for the and is still a of developing AMR is an issue solid organ in this the specific 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. The of HLA in renal for and an that Class II has demonstrated that the development of dnDSA, Class II HLA is a major cause of renal loss. The of chronic antibody-mediated rejection is by immune to the of the and The early of months graft the for the of and the of new treatment Risk factors for development Class II HLA nonadherence to IS and prior cellular rejection. the treatment of chronic antibody-mediated rejection is that to the risk factors be The of HLA on renal allograft outcomes reported in Transplant over the last years from the demonstrated that an in the number of and in renal patients with a higher incidence of acute rejection and graft and with renal after reported a of HLA on graft survival in the of kidney and and demonstrated that and graft survival and rates of rejection in the in to the number of A and and antigens in over of over A of HLA (particularly for HLA Class has also reported for the of from in the The of kidney that has in by The of HLA as a of and renal outcomes has reported on over renal from the Renal and that the in graft survival to HLA over and that that HLA to be reported that failure of in increased rates of which the of HLA transplantation. However, on the development of de novo antibodies HLA antigens (particularly Class as a major cause of renal allograft and loss the to better HLA of and in an to graft The of DSA, as by the of a the of demonstrated in the of and in the of in the by in early of humoral acute and chronic antibody-mediated rejection by in the the in the of DSA and on allograft has resulted from the development of solid-phase assays for antibody detection that to the role of DSA in the of as a of antibody-mediated by and the recognition of the and in the as the for antibody-mediated inflammation in the the of these has clear that that to antibody-mediated allograft The to acute AMR that in patients DSA the of transplantation. The to the of that in patients after transplantation. DSA renal early AMR has reported in in which DSA in the cytotoxicity and other by the with solid-phase assays reported on patients with a negative cytotoxicity and of an acute rejection a of months of these patients which caused by DSA in of the patients and by II DSA in the after the with The authors that patients with AMR to that or or outcomes patients treatment the that or or in an from the in reported on of negative or the the by cytotoxicity or by of and The from these patients also for DSA by solid-phase and reported as of the of the for Class and Class II HLA The outcomes reported early AMR and graft loss. a between the of the for antibody detection and the early AMR with antibodies by with antibodies a greater by and with antibodies with a higher DSA of renal caused by has also a of in the and a of of is a of and from and for the presence of DSA the solid-phase assays with an of these patients negative for DSA the of and protocol biopsies 6 months later that of that with 6 months a incidence of in the and a years. The incidence of of is that to patients the of of the of the to the that of patients with graft an of inflammation in the and in the on renal The subclinical of antibody-mediated rejection in patients to IS these patients graft with a of of patients with DSA with of graft and a that a of rejection with rejection and AMR these patients The development of the of graft loss in a and resulted in a graft survival years (Table The of on graft survival has reported in other of which the between outcomes and Class II DSA in and in others HLA mismatching (particularly the Class II HLA of also to be a of in and in from the the of the IS regimen also to be an factor for the development of patients from to DSA and AMR on that in patients with with patients that inadequate from nonadherence or reduction in the of the IS can the risk of of graft loss is of that out that prior be a risk factor for the development of and that of that early subclinical cellular rejection with an increased risk of and later is also that in that inflammation in of patients that of Class II HLA on the in as a of and that HLA in Moreover, a from the in has that in a of renal DSA the of with acute cellular rejection by or protocol graft inflammation and an in new Class II DSA patients cellular rejection. graft inflammation and new Class II DSA with an increased risk of graft loss AMR for AMR with DSA, the reported that treatment and antibody and resulted in better outcomes treatment However, a the Transplant benefit of over in patients with AMR with and The of solid-phase assays for antibody detection and the of over desensitization in a incidence of early AMR caused by dnDSA, to A major for this is that is caused by Class II DSA, which is to to and to the of AMR and is the the of solid-phase assays and the number of immunological risk of the of Class II mismatching be and the of Class II HLA and the of the of Class II a risk for development risk minimization and the of IS of in the early of nonadherence be a in the The of by as a major cause of renal allograft loss is an Moreover, the of a subclinical phase graft an for and the of new treatment the for DSA in with on patients risk patients minimization protocols, and The treatment of is and the The introduction of new IS and better management of kidney over the last to improved graft survival after kidney by the of early graft loss However, graft survival is still an and to and the of with a graft which is a leading cause of allograft loss patients failure which is an cause of renal immunological and nonimmunological factors as to allograft and failure after kidney such as HLA or retransplantation detection is and to patients a higher the for the of graft and failure is to a the of by the is when the presence of chronic and a such the of other the in the for the causes of allograft failure is to Late graft and failure defined in the and to because leading to the that because of chronic allograft nephropathy a histological that to a specific that and from the The of AMR has because of the that the detection of in the is to this when in late The of negative AMR has in the and attributed to or calcineurin Thus, patients late AMR with caused by de novo donor-specific HLA antibodies, II demonstrated that AMR or the major cause of late kidney failure The that late graft failure in with of antibody-mediated and also that with histological of to such a this a from the that and histological from with antibody that of the with interstitial that could be attributed to specific causes and to The causes of graft loss attributed to rejection nephropathy or and acute rejection of the specific cause could be to the failure a out by allograft a with the of the cause of a of to failure, which attributed to AMR or rejection nephropathy and because of graft AMR or that the risk of failure is higher when is an kidney the cause of failure and could be attributed to or acute cellular rejection Thus, in these the major causes of allograft failure antibody-mediated rejection and demonstrated is a major cause of late kidney failure is a to The reported in is on the to from to is after and as late rejection. the of nonadherence and outcomes nonadherence in patients to failure patients late AMR or rejection, or of antibody-mediated the with failure, with of the rejection (Fig. the patients with late rejection nonadherence or reduction of IS treatment caused by in of the causes of graft in the the of graft loss is an to outcomes in kidney can be attributed to specific causes is and The causes of late graft failure antibody-mediated rejection and causes nephropathy and failure in the of an is a that as a late rejection and graft failure by of to be in patients is a major cause of graft failure over is the for López Hoyos, David San Segundo, and Manuel the role of antibodies in has clear the of the last the in the last of new solid-phase assays and with has the importance of de novo reported by an increased risk of graft loss in renal when by and the authors of kidney patients for the has as a for is a that with HLA is defined by an after with the the recognition of the by the antibody in a The by the of the of the with the of allowing as or of could be considered for and graft also the detection of low titers of donor-specific (DSA) that by the role of DSA by on renal outcomes has However, reported the of a the presence of with a higher risk for AMR and increased the risk for graft failure in the presence of a negative the authors point for the graft loss risk with the development of DSA and Thus, when of the management of kidney in the the presence and of DSA HLA-A, and also the detection of antibody specificities such as -DR, and Considering the importance of these new and the of the the of has the in with the of and HLA and the of by the the of the the that the in by the and the is defined by a by of such a point or and also the detect from the that the of could be that the be as that the presence of must be reported has in kidney can be after solid organ transplantation. with renal the presence of in and transplants is with a graft survival a role in the outcomes of the development of de novo the increases in or the to and the the risk of graft loss the presence of DSA is in DSA a months after transplantation. in DSA with the of is in the this is a by that of a of after transplantation. of these DSA and De novo DSA resulted in graft survival and survival in a a the authors that the risk of graft loss is with the of DSA of to the role of HLA in graft of the organ AMR with in the DSA, and of graft the influence of in the of chronic rejection by monitoring According to is a between graft survival and the presence of specific or as with patients with or patients with of DSA and in related with a higher of graft failure within after transplantation. the development of in and patients a kidney The development of of within years of patients of patients over the Graft failure of within years after rates with (Table from an Anti-HLA the after kidney transplantation. graft the presence of DSA and Class II as risk factors for the development of and graft loss and patients with a to (5). the other Class A to an role in graft can be considered useful of risk for graft loss the role of detection and monitoring could be useful in situations, such as desensitization protocols, monitoring of patients with DSA and negative complement-dependent cytotoxicity (CDC), when humoral rejection is or when in the IS therapy. The and treatment of AMR is in a of this monitoring can be useful in the of the of in the of from to this demonstrated that as to is with an increased risk of DSA and AMR from a in a higher of in patients from a calcineurin (CNI) to an when to patients a between antibody and the of that to can be followed by the early of de novo in patients with and this be early after The importance of between and be in when considering the of antibody in the the of the is to a and the humoral to allograft rejection an of this be into when a IS, because to be the of in IS Moreover, by and also be considered because the humoral as antibodies or could and negative by the role of the immune assays as a new in the detection and of which can be in solid organ new the detection of by other The influence of SPA in the detection of DSA and to be in the of is in The of is in the of the of IS and the to is in the humoral rejection. treatment could María G. Crespo-Leiro, Raquel Marzoa-Rivas, Eduardo Barge-Caballero, María J. The acute rejection of a is an the graft and the the of an immune with and antibody-mediated is the that has in acute cellular rejection is an entity can be in by and a of as to and treatment in years has in as humoral rejection because of histological as rejection, because in AMR and of and the incidence and of in years as a of in the incidence of AMR to be AMR is with graft rejection also to be an cause of graft and allograft However, of the incidence and of and of is by the of and in the the reported incidence of AMR has from when on of graft in the of or cellular to when on the of rejection by antibodies the early of the rejection caused by a major with a caused by the of to such antibodies and the of The of the antigens in AMR is which when and and Class II AMR damage and after the and of the the of and that and immune a of and by of and the of the and can and the of and other whereas low of or can in and with the is for understanding the of by in the of AMR AMR early by and in other and with of or the of acute rejection on cellular of humoral rejection the of for or or in the of cellular to be in as defined the in AMR as a the of histological for of The of the of AMR by also and for of acute graft while that graft is in of early AMR and of late The that an of graft AMR has in AMR to increased risk of graft and and a on AMR in solid organ considered the of histological and antibody to donor-specific antigens to subclinical humoral rejection the to of AMR as to the The and in with and and on and The to a of in and has on the of improved of graft can for in the of histological of AMR and the of this is the on AMR in solid organ considered that the presence of and antibodies, in the of histological humoral rejection of the or subclinical or an later attributed to the by graft of such as the factor which of the The in in to of AMR by the of a in in which revealed the of of and immunological the that over of these of AMR on the of graft in the of A in to some The major of this that AMR be on the of the of and to be as to management as Moreover, immunological for histological for the immunological monitoring is in immunological is to be and and months AMR is suspected on and and on after of is as allowing of a of (Table of this also on the for a the of or and of as of and the antigens to be in to The for of AMR Heart Lung Transplant also an on for the of antibodies donor-specific antigens and Class II and other tests these to be for and and months and AMR is suspected on on the treatment of AMR The and whereas and the an of in to the and of to be this is that the on in the of and the of and IS to the of the role of AMR in this entity is still in transplantation. in this and the role of the AMR in the graft graft rejection has the in transplantation. is still a and with outcomes The of has considered from the The humoral in rejection has partly as a of the availability of new solid-phase that some patients antibodies prior or transplantation) which be for or or acute rejection to antibodies, the development of DSA after has as a risk factor for acute and chronic rejection acute rejection, in is the graft loss. allograft is by a and of the which the of is a major in because to a graft risk factors with has a with the of humoral and The development of HLA antibodies is as an risk Thus, humoral has as factor for as in other the presence of and in related with a early de novo development of antibodies has with increased acute and chronic rejection and graft survival in and a the of to humoral rejection in this of the to kidney whereas AMR in to is in when a the of role in the entity is in other The authors of this the role of humoral in rejection on the presence of antibodies and the of in the after transplantation. DSA development is in transplantation. the Antibodies after Lung an that of patients DSA after Class Class and Class and Class in a of and antibodies in of of DSA, which with a in graft and survival The development of DSA early after the other and histological of rejection a that patients with antibodies in the after transplantation. The presence of DSA, and de has with and DSA has with an increased of acute cellular rejection and the of DSA has related with graft chronic and survival Moreover, a incidence of has in graft regardless of The of AMR is on the presence of Class and Class II DSA and the of for in the recognition of humoral in transplantation. the last the development of new has the of HLA antibody The of these new by the of low of DSA, HLA Class and Class and the antibody with specific graft pathology. that DSA other is to of or is related to the in biopsies biopsies in because of the risk for patients and low and has the for the presence of allograft rejection. with a and the is an tool to the graft after transplantation. a by after from the last years patients with AMR that damage the of findings, considered of leading to tests in of antibodies or such as is a of humoral rejection, and can other histological of chronic rejection. the importance of protocol biopsies and Considering the of specific for AMR a the of and for the AMR graft DSA and this the in other be also for the (Table The of chronic humoral rejection, for the AMR with or is to DSA or rejection because of the of as a out protocol biopsies with DSA is in this AMR be in a AMR is an issue in transplantation. and to development after graft still to be AMR and DSA development be in the incidence of chronic graft and an on be to to within the after biopsies and DSA and and on graft a in transplantation. years and demonstrated a temporary dynamic in the course of in from the of to years The of histological renal allograft damage includes a by tubule-interstitial inflammation that is the months and to in some tubule-interstitial damage after a months after and of patients by followed by a later phase of chronic allograft nephropathy defined by arteriolar hyalinosis and glomerulosclerosis. The early of interstitial in and with a graft survival early subclinical inflammation is with the development of in biopsies and with graft survival rates these the biopsies considering the presence or of inflammation or later in of the of biopsies as inflammation or the with graft survival a higher risk of developing in to the presence of interstitial inflammation in protocol biopsies within the 6 months the the of a temporary between an early inflammation in patients and the of histological such as and (Fig. The by which early inflammation to is that a The presence of is with the graft whereas and in graft of the between early inflammation by of protocol later of histological and graft antibody-mediated DSA, specific interstitial inflammation and inflammation with interstitial and this subclinical inflammation be The benefit of treating subclinical rejection, by early protocol demonstrated years a that patients with subclinical rejection in early biopsies months or with of a in acute rejection a reduced chronic 6 and a better renal months patients in the to biopsies months 6 and and patients followed a protocol and and the of subclinical inflammation months and a later by patients to in which biopsies the of and months after in to the and II an patients a IS regimen of a or an or and and the of subclinical inflammation and biopsies in the patients in the with of inflammation in protocol biopsies months or whereas patients protocol biopsies A between in the with a between early protocol biopsies and 6 and months after transplantation. the of treating subclinical inflammation on graft However, and in a a with a patients an IS regimen with to a and 6 or a and 6 this between in and renal in the 6 that early protocol biopsies the short-term outcomes in patients this of benefit to the low of subclinical rejection in the The low immunological risk of patients and the IS on could the low of subclinical rejection. Based on these could that is to graft by treating subclinical inflammation and that the IS regimen and can influence the of subclinical this that the of subclinical inflammation on the IS treatment in a the of subclinical inflammation with as with and in a that or with subclinical inflammation and after and years of or be according to in patients on to between and months after with higher increases in chronic pathology. the with these that subclinical and can be with has the by of or these However, be the increased risk of allograft rejection has is the of reduction on the kidney protocol minimization with a by and patients with a months after transplantation. that to from or patients in the improved renal a higher risk of acute rejection as with the months that patients acute rejection in the higher incidence of in the considered risk factors for acute rejection after The the of on inflammation in kidney protocol biopsies is and patients on that into a low of the and a from between renal protocol biopsies demonstrated a of allograft in the the other a on to or years after between in the rates of acute rejection in the of by of protocol protocol the be could be by the of to the such as or and in can a by and patients kidney to of the or The that rejection graft and renal years after in and However, a higher incidence of chronic on protocol biopsies in the the other out an of the and in this biopsies from patients in the and IS that be with a reduced early graft with of the the of the IS with or on and renal is the this renal months after to from to or to with renal improved in the the in of between the biopsies of a of the of subclinical inflammation higher incidence in the in the to the of treatment and on renal patients in with and and

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.