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      Antibody-mediated rejection after lung transplantation

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          Abstract

          Antibody-mediated rejection (AMR) has been identified as a significant form of acute allograft dysfunction in lung transplantation. The development of consensus diagnostic criteria has created a uniform definition of AMR; however, significant limitations of these criteria have been identified. Treatment modalities for AMR have been adapted from other areas of medicine and data on the effectiveness of these therapies in AMR are limited. AMR is often refractory to these therapies, and graft failure and death are common. AMR is associated with increased rates of chronic lung allograft dysfunction (CLAD) and poor long-term survival. In this review, we discuss the history of AMR and describe known mechanisms, application of the consensus diagnostic criteria, data for current treatment strategies, and long-term outcomes. In addition, we highlight current gaps in knowledge, ongoing research, and future directions to address these gaps. Promising diagnostic techniques are actively being investigated that may allow for early detection and treatment of AMR. We conclude that further investigation is required to identify and define chronic and subclinical AMR, and head-to-head comparisons of currently used treatment protocols are necessary to identify an optimal treatment approach. Gaps in knowledge regarding the epidemiology, mechanisms, diagnosis, and treatment of AMR continue to exist and future research should focus on these aspects.

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          Most cited references88

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          The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights

          Since the discovery of glucocorticoids in the 1940s and the recognition of their anti-inflammatory effects, they have been amongst the most widely used and effective treatments to control inflammatory and autoimmune diseases. However, their clinical efficacy is compromised by the metabolic effects of long-term treatment, which include osteoporosis, hypertension, dyslipidaemia and insulin resistance/type 2 diabetes mellitus. In recent years, a great deal of effort has been invested in identifying compounds that separate the beneficial anti-inflammatory effects from the adverse metabolic effects of glucocorticoids, with limited effect. It is clear that for these efforts to be effective, a greater understanding is required of the mechanisms by which glucocorticoids exert their anti-inflammatory and immunosuppressive actions. Recent research is shedding new light on some of these mechanisms and has produced some surprising new findings. Some of these recent developments are reviewed here.
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            The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-Fifth Adult Lung and Heart–Lung Transplant Report—2018; Focus Theme: Multiorgan Transplantation

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              Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection.

              In 1990, an international grading scheme for the grading of pulmonary allograft rejection was adopted by the International Society for Heart and Lung Transplantation (ISHLT) and was modified in 1995 by an expanded group of pathologists. The original and revised classifications have served the lung transplant community well, facilitating communication between transplant centers with regard to both patient management and research. In 2006, under the direction of the ISHLT, a multi-disciplinary review of the biopsy grading system was undertaken to update the scheme, address inconsistencies of use, and consider the current knowledge of antibody-mediated rejection in the lung. This article summarizes the revised consensus classification of lung allograft rejection. In brief, acute rejection is based on perivascular and interstitial mononuclear infiltrates, Grade A0 (none), Grade A1 (minimal), Grade A2 (mild), Grade A3 (moderate) and Grade A4 (severe), as previously. The revised (R) categories of small airways inflammation, lymphocytic bronchiolitis, are as follows: Grade B0 (none), Grade B1R (low grade, 1996, B1 and B2), Grade B2R (high grade, 1996, B3 and B4) and BX (ungradeable). Chronic rejection, obliterative bronchiolitis (Grade C), is described as present (C1) or absent (C0), without reference to presence of inflammatory activity. Chronic vascular rejection is unchanged as Grade D. Recommendations are made for the evaluation of antibody-mediated rejection, recognizing that this is a controversial entity in the lung, less well developed and understood than in other solid-organ grafts, and with no consensus reached on diagnostic features. Differential diagnoses of acute rejection, airway inflammation and chronic rejection are described and technical considerations revisited. This consensus revision of the working formulation was approved by the ISHLT board of directors in April 2007.
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                Author and article information

                Journal
                Ann Transl Med
                Ann Transl Med
                ATM
                Annals of Translational Medicine
                AME Publishing Company
                2305-5839
                2305-5847
                March 2020
                March 2020
                : 8
                : 6
                : 411
                Affiliations
                [1]Division of Pulmonary & Critical Care, Washington University School of Medicine , Saint Louis, MO, USA
                Author notes

                Contributions: (I) Conception and design: All authors; (II) Administrative support: RR Hachem; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: None; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                Correspondence to: Amit I. Bery, MD. Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, 660 S Euclid Avenue, Campus Box 8052, Saint Louis, MO 63108, USA. Email: amit.bery@ 123456wustl.edu .
                Article
                atm-08-06-411
                10.21037/atm.2019.11.86
                7186640
                32355855
                9339766f-a04f-460c-a7fe-4c8b35137878
                2020 Annals of Translational Medicine. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 21 July 2019
                : 08 November 2019
                Categories
                Review Article on Strategies to Achieve Long-Term Success of Lung Transplantation

                lung transplantation,graft rejection,allograft tolerance,acute lung injury,complement component,complement c4d,diagnostic techniques and procedures,plasmapheresis,intravenous immunoglobulins (ivig),rituximab,eculizumab,outcome assessment

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