Current Opinion in Organ Transplantation最新文献

Purpose of review: The implementation of highly sensitive immune assays measuring anti-human leukocyte antigen (HLA) antibodies has modified alloimmune risk stratification and diagnosis of rejection. Nonetheless, anti-HLA antibodies represent the downstream effector mechanism of the B-cell response. Better characterizing the cellular components of the humoral immune response (including memory B cells (mBCs) and long-lived plasma cells) could help to further stratify the alloimmune risk stratification and enable discovery of new therapeutic targets. Several tests that characterize HLA-specific mBCs, either functionally or phenotypically, have been developed in the last years, showing promising applications as well as some limitations.

Recent findings: Functional assays involving ex vivo polyclonal activation of mBC have been refined to allow the detection of HLA-specific mBC capable of producing anti-HLA Abs, using different and complementary detection platforms such as multiplex Fluorospot and single antigen bead assay on culture supernatants. Detection of circulating HLA-specific B cells by flow cytometry remains hindered by the very low frequency of HLA-specific mBC.

Summary: Technological refinements have allowed the development of tests detecting HLA-specific mBC. Further evaluation of these assays in clinical trials, both for immune risk stratification and to assess treatment efficacy (desensitization strategies, rescue therapies for ABMR) are now urgently needed.

Purpose of review: The revised United States heart organ allocation system was launched in October 2018. In this review, we summarize this United Network for Organ Sharing (UNOS) policy and describe intended and unintended consequences.

Recent findings: Although early studies published after the change suggested postheart transplant survival declined at 6 months and 1 year, recent publications with longer follow-up time have confirmed comparable posttransplant survival in adjusted models and several patient cohorts. Moreover, the new allocation decreased overall waitlist time from 112 to 39 days ( P  < 0.001). Mean ischemic time increased because of greater distances traveled to acquire donor hearts under broader sharing. Despite the intention to decrease exception requests by expanding the number of priority tiers to provide more granular risk stratification, ∼30% of patients remain waitlisted under exception status. Left-ventricular assist device (LVAD) implants are declining and the number of LVAD patients on the transplant list has decreased dramatically after the allocation system change.

Summary: As the next allocation system is developed, it is imperative to curtail the use of temporary mechanical support as a strategy solely for listing purposes, identify attributes that more clearly stratify the severity of illness, provide greater oversight of exception requests, and address concerns regarding patients with durable LVADs.

Purpose of review: De novo HLA-DQ antibodies are the most frequently observed after solid-organ allotransplantation; and are associated with the worse adverse graft outcomes compared with all other HLA antibodies. However, the biological explanation for this observation is not yet known. Herein, we examine unique characteristics of alloimmunity directed specifically against HLA-DQ molecules.

Recent findings: While investigators attempted to decipher functional properties of HLA class II antigens that may explain their immunogenicity and pathogenicity, most early studies focused on the more expressed molecule - HLA-DR. We here summarize up-to-date literature documenting specific features of HLA-DQ, as compared to other class II HLA antigens. Structural and cell-surface expression differences have been noted on various cell types. Some evidence suggests variations in antigen-presenting function and intracellular activation pathways after antigen/antibody interaction.

Summary: The clinical effects of donor-recipient incompatibility at HLA-DQ, the risk of generating de novo antibodies leading to rejection, and the inferior graft outcomes indicate increased immunogenicity and pathogenicity that is unique to this HLA antigen. Clearly, knowledge generated for HLA-DR cannot be applied interchangeably. Deeper understanding of features unique to HLA-DQ may support the generation of targeted preventive-therapeutic strategies and ultimately improve solid-organ transplant outcomes.

Purpose of review: This review aims to summarize the highlights from recent research that involved pathological and molecular analysis of kidney allografts.

Recent findings: As the research on antibody-mediated rejection (AMR) continues to evolve, studies are focused on identification through transcript studies of pathogenetic pathways involved in the development of AMR as well as refinement of diagnostic methods either by correlating Banff pathologic lesions with clinical and molecular data or by machine learning. Of note, the past year has generated high impact research that underscore the importance of pathologic and molecular correlations and detection of transcripts or gene sets that would aid prognostication. The studies involving refinement of pathologic criteria also highlight the continuous efforts to achieve diagnostic accuracy and standardization.

Summary: Research involving histologic and molecular characteristics that define AMR are central to identification and understanding of pathogenetic pathways and remain critical in the development of diagnostic criteria.

Purpose of review: For sensitized heart transplant candidates who have antibodies to human leukocyte antigens (HLA), finding a suitable donor can be challenging and can lead to adverse waitlist outcomes. In recent years, the number of sensitized patients awaiting heart transplantation has increased likely due to the use of durable and mechanical circulatory support as well as increasing number of candidates with underlying congenital heart disease.

Recent findings: Advances in the assessment of HLA antibodies allow for identification of heart transplant candidates who may benefit from desensitization strategies to widen the donor pool and mitigate the risk of adverse posttransplant outcomes.

Summary: Antibody sensitization is a barrier to successful heart transplantation and strategies to identify sensitized patients, stratify their risk, and mitigate this risk through desensitization is crucial to optimize the quality of life and survival of HT recipients.

Purpose of review: The number of dual organ transplantations (DOT) are steadily increasing over the past few years. This is both a reflection of increasing complexity and advanced disease process in the patients and greater transplant center experience with performing dual organ transplants. Due to lack of standardization of the process, there remains significant center-based variability in patient selection, perioperative and long-term management of these patients.

Recent findings: Overall posttransplant outcomes for DOT have been acceptable with some immunological advantages because of partial tolerance offered by the second organ. These achievements should, however, be balanced with the ethical implications of bypassing the patients who are listed for single organ transplantation because of the preferential allocation of organs for DOT.

Summary: The field of DOT is expanding rapidly, with good long-term outcomes. There is an urgent need for guidelines to standardize the process of patient selection and listing dual organ transplantation.

Purpose of review: In the United States, candidates with hepatocellular carcinoma (HCC) meeting standardized qualifying criteria receive similar priority on the liver transplant waiting list through Model for End-Stage Liver Disease exception points, without consideration of the dropout risk or relative expected benefit from liver transplantation. A more nuanced allocation scheme for HCC is needed to better represent the individual urgency for liver transplant and optimize organ utility. In this review, we discuss the development of HCC risk prediction models for practical use in liver allocation.

Recent findings: HCC is a heterogenous disease that requires improved risk stratification for patients who fall within current transplant eligibility criteria. Several models have been proposed, though none have been adopted in clinical practice or liver allocation to date, due to various limitations.

Summary: Improved HCC risk stratification for liver transplant candidates is needed to more accurately represent their urgency for transplant, with continued attention to the potential impact on post-liver transplant outcomes. Plans to implement a continuous distribution model for liver allocation in the United States may provide an opportunity to re-consider a more equitable allocation scheme for patients with HCC.

Purpose of study: The purpose of this review is to provide the current state of immunosuppression therapy in kidney transplant recipients (KTR) with HIV and to discuss practical dilemmas to better understand and manage these patients.

Recent findings: Certain studies find higher rates of rejection, which raises the need to critically assess the approach to immunosuppression management in HIV-positive KTR. Induction immunosuppression is guided by transplant center-level preference rather than by the individual patient characteristics. Earlier recommendations expressed concerns about the use of induction immunosuppression, especially utilizing lymphocyte-depleting agents; however, updated guidelines based on newer data recommend that induction can be used in HIV-positive KTR, and the choice of agent be made according to immunological risk. Likewise, most studies point out success with using first-line maintenance immunosuppression including tacrolimus, mycophenolate, and steroids. In selected patients, belatacept appears to be a promising alternative to calcineurin inhibitors with some well established advantages. Early discontinuation of steroids in this population carries a high risk of rejection and should be avoided.

Summary: Immunosuppression management in HIV-positive KTR is complex and challenging, mainly because of the difficulty of maintaining a proper balance between rejection and infection. Interpretation and understanding of the current data towards a personalized approach of immunosuppression could improve management in HIV-positive KTR.

Purpose of review: Intestinal and multivisceral transplantation (ITx, MVTx) is the cornerstone in treatment of irreversible intestinal failure (IF) and complications related to parenteral nutrition. This review aims to highlight the unique aspects of the subject in pediatrics.

Recent findings: Etiology of intestinal failure (IF) in children shares some similarity with adults but several unique considerations when being evaluated for transplantation will be discussed. Owing to significant advancement in IF management and home parenteral nutrition (PN), indication criteria for pediatric transplantation continues to be updated. Outcomes have continued to improve with current long-term patient and graft survival in multicenter registry reports reported at 66.1% and 48.8% at 5 years, respectively. Pediatric specific surgical challenges such abdominal closure, post transplantation outcomes, and quality of life are discussed in this review.

Summary: ITx and MVTx remain lifesaving treatment for many children with IF. However long-term graft function is still a major challenge.