A comprehensive list of recommendations is provided covering the technical and pretransplantation and posttransplantation monitoring of HLA antibodies in solid organ transplantation. The recommendations are intended to provide state-of-the-art guidance in the use and clinical application of recently developed methods for HLA antibody detection when used in conjunction with traditional methods.

In an analysis of biopsies from an apparently homogeneous group of stable, long-term pediatric liver transplant recipients with consistently normal liver test results, we found evidence of chronic graft injury (inflammation and/or fibrosis). Biopsy samples with interface activity had a gene expression pattern associated with TCMR.

OverviewIn renal transplantation, a positive cytotoxic crossmatch between donor cells and recipient serum is associated with early rejection or graft loss and was the driving force behind the establishment of HLA laboratories. Initially, crossmatches were performed by relatively insensitive techniques [e.g. leukoagglutination and direct complement-dependent cytotoxicity (CDC) of target cells]. A negative result justified proceeding, while a positive crossmatch was considered a contraindication to renal transplantation. However, the underlying premises driving this practice, namely that (i) all positive reactions were the result of relevant (i.e. HLA) antibodies that could lead to allograft rejection; and (ii) all negative reactions predicted long-term graft survival were known to be incorrect. From its first clinical description, the simple complementdependent assay was recognized as neither sufficiently specific nor sensitive to identify all relevant antibodies. Over time, more sensitive and specific lymphocyte crossmatch assays were developed that effectively decreased the incidence of early antibody-mediated rejection.In recent years, advances in immunosuppressive therapy have led clinicians to ask whether antibodies identified by these more sophisticated crossmatch techniques represent a contraindication to transplantation. To answer this question, it is essential to prove (or disprove) that antibodies specific for donor HLA antigens are present in recipient sera. A critical analysis of the literature revealed that the majority of studies failed to provide sufficient evidence to ensure that positive (as well as negative) crossmatches were correctly assigned. Indeed, few investigators performed the labor-intensive studies necessary to document that positive crossmatches were the result of antibodies specific for donor HLA antigens. Furthermore, the testing methodology used in those studies was relatively insensitive compared with current and emerging technologies. Given these limitations, we believe it is essential to re-examine the conclusions of studies that formed the basis of our current crossmatch paradigms.Just as the clinical application of calcineurin inhibitors revolutionized transplant medicine, the recent development of HLA antigen specific solid-phase assays (i.e., ELISA and microparticle-based flow cytometric assays) has similarly revolutionized our ability to detect HLA antibodies. Specifically, by documenting whether patient sera possess donor-reactive HLA antibodies, a lymphocyte crossmatch can now be more reliably interpreted. Indeed, with solidphase data, a positive lymphocyte crossmatch can now be categorized as (i) clinically irrelevant, (ii) a risk factor for rejection or graft loss, or (iii) a contraindication to renal transplantation. It is our position that only with accurate risk assessment can desensitization protocols [e.g., intervenous gamma globulin (IVIG) with or without plasmaphereisis] be optimally applied.

The presence of preexisting (memory) or de novo donor-specific HLA antibodies (DSAs) is a known barrier to successful long-term organ transplantation. Yet, despite the fact that laboratory tools and our understanding of histocompatibility have advanced significantly in recent years, the criteria to define presence of a DSA and assign a level of risk for a given DSA vary markedly between centers. A collaborative effort between the American Society for Histocompatibility and Immunogenetics and the American Society of Transplantation provided the logistical support for generating a dedicated multidisciplinary working group, which included experts in histocompatibility as well as kidney, liver, heart, and lung transplantation. The goals were to perform a critical review of biologically driven, state-of-the-art, clinical diagnostics literature and to provide clinical practice recommendations based on expert assessment of quality and strength of evidence. The results of the Sensitization in Transplantation: Assessment of Risk (STAR) meeting are summarized here, providing recommendations on the definition and utilization of HLA diagnostic testing, and a framework for clinical assessment of risk for a memory or a primary alloimmune response. The definitions, recommendations, risk framework, and highlighted gaps in knowledge are intended to spur research that will inform the next STAR Working Group meeting in 2019.

RTX can be safely administered and may be an effective agent to reduce high-titer anti-HLA Abs in subjects awaiting kidney transplantation.