The XVth Banff Conference on Allograft Pathology the Banff Workshop Heart Report: Improving the diagnostic yield from endomyocardial biopsies and Quilty effect revisited

Jean-Paul Duong Van Huyen, Marny Fedrigo, Gregory A Fishbein, Ornella Leone, Desley Neil, Charles Marboe, Eliot Peyster, Jan von der Thüsen, Alexandre Loupy, Michael Mengel, Monica P Revelo, Benjamin Adam, Patrick Bruneval, Annalisa Angelini, Dylan V Miller, Gerald J Berry, Jean-Paul Duong Van Huyen, Marny Fedrigo, Gregory A Fishbein, Ornella Leone, Desley Neil, Charles Marboe, Eliot Peyster, Jan von der Thüsen, Alexandre Loupy, Michael Mengel, Monica P Revelo, Benjamin Adam, Patrick Bruneval, Annalisa Angelini, Dylan V Miller, Gerald J Berry

Abstract

The XVth Banff Conference on Allograft Pathology meeting was held on September 23-27, 2019, in Pittsburgh, Pennsylvania, USA. During this meeting, two main topics in cardiac transplant pathology were addressed: (a) Improvement of endomyocardial biopsy (EMB) accuracy for the diagnosis of rejection and other significant injury patterns, and (b) the orphaned lesion known as Quilty effect or nodular endocardial infiltrates. Molecular technologies have evolved in recent years, deciphering pathophysiology of cardiac rejection. Diagnostically, it is time to integrate the histopathology of EMBs and molecular data. The goal is to incorporate molecular pathology, performed on the same paraffin block as a companion test for histopathology, to yield more accurate and objective EMB interpretation. Application of digital image analysis from hematoxylin and eosin (H&E) stain to multiplex labeling is another means of extracting additional information from EMBs. New concepts have emerged exploring the multifaceted significance of myocardial injury, minimal rejection patterns supported by molecular profiles, and lesions of arteriolitis/vasculitis in the setting of T cell-mediated rejection (TCMR) and antibody-mediated rejection (AMR). The orphaned lesion known as Quilty effect or nodular endocardial infiltrates. A state-of-the-art session with historical aspects and current dilemmas was reviewed, and possible pathogenesis proposed, based on advances in immunology to explain conflicting data. The Quilty effect will be the subject of a multicenter project to explore whether it functions as a tertiary lymphoid organ.

Keywords: classification systems; clinical research/practice; heart (allograft) function/dysfunction; heart transplantation/cardiology; pathology/histopathology; rejection.

© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.

References

REFERENCES

    1. Loupy A, Duong Van Huyen JP, Hidalgo L, et al. Gene expression profiling for the identification and classification of antibody-mediated heart rejection. Circulation. 2017;135(10):917-935.
    1. Holweg CTJ, Potena L, Luikart H, et al. Identification and classification of acute cardiac rejection by intragraft transcriptional profiling. Circulation. 2011;123(20):2236-2243.
    1. Parkes MD, Aliabadi AZ, Cadeiras M, et al. An integrated molecular diagnostic report for heart transplant biopsies using an ensemble of diagnostic algorithms. J Heart Lung Transplant. 2019;38(6):636-646.
    1. Afzali B, Chapman E, Racapé M, et al. Molecular assessment of microcirculation injury in formalin-fixed human cardiac allograft biopsies with antibody-mediated rejection. Am J Transplant. 2017;17(2):496-505.
    1. Adam N, Coutance G, Viailly P-J, et al. Reverse transcriptase multiplex ligation-dependent probe amplification in endomyocardial biopsies for the diagnosis of cardiac allograft rejection. J Heart Lung Transplant. 2020;39(2):115-124.
    1. Haas M, Loupy A, Lefaucheur C, et al. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant. 2018;18(2):293-307.
    1. Peyster EG, Madabhushi A, Margulies KB. Advanced morphologic analysis for diagnosing allograft rejection: the case of cardiac transplant rejection. Transplantation. 2018;102(8):1230-1239.
    1. Esteva A, Kuprel B, Novoa RA, et al. Dermatologist-level classification of skin cancer with deep neural networks. Nature. 2017;542(7639):115-118.
    1. Nirschl JJ, Janowczyk A, Peyster EG, et al. A deep-learning classifier identifies patients with clinical heart failure using whole-slide images of H&E tissue. PLoS ONE. 2018;13(4):e0192726.
    1. Billingham ME, Cary NR, Hammond ME, et al. A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: Heart Rejection Study Group. The International Society for Heart Transplantation. J Heart Transplant. 1990;9(6):587-593.
    1. Berry GJ, Burke MM, Andersen C, et al. The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation. J Heart Lung Transplant. 2013;32(12):1147-1162.
    1. van den Bosch TPP, Caliskan K, Kraaij MD, et al. CD16+ monocytes and skewed macrophage polarization toward M2 type hallmark heart transplant acute cellular rejection. Front Immunol. 2017;8.
    1. Fedrigo M, Leone O, Burke MM, et al. Inflammatory cell burden and phenotype in endomyocardial biopsies with antibody-mediated rejection (AMR): a multicenter pilot study from the AECVP: inflammatory cell burden in EMBs with AMR. Am J Transplant. 2015;15(2):526-534.
    1. Calvani J, Terada M, Lesaffre C, et al. In situ multiplex immunofluorescence analysis of the inflammatory burden in kidney allograft rejection: a new tool to characterize the alloimmune response. Am J Transplant. 2020;20(4):942-953.
    1. Potena L, Manfredini V, Leone O. Graft failure/dysfunction: clinical issues and role of endomyocardial biopsy. In Leone O, Angelini A, Bruneval P, Potena L, eds. The Pathology of Cardiac Transplantation: A Clinical andPathological Perspective. Cham, Switzerland: Springer International Publishing; 2016;155-169.
    1. Stewart S, Winters GL, Fishbein MC, et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant. 2005;24(11):1710-1720.
    1. Bruneval P, Angelini A, Miller D, et al. The XIIIth Banff Conference on Allograft Pathology: the Banff 2015 heart meeting report: improving antibody-mediated rejection diagnostics: strengths, unmet needs, and future directions. Am J Transplant. 2017;17(1):42-53.
    1. Fyfe B, Loh E, Winters GL, Couper GS, Kartashov AI, Schoen FJ. Heart transplantation-associated perioperative ischemic myocardial injury. Morphological features and clinical significance. Circulation. 1996;93(6):1133-1140.
    1. Doran H, Neil DAH. Pathological non-rejection findings in the endomyocardial biopsy. In Leone O, Angelini A, Bruneval P, eds. The Pathology of Cardiac Transplantation: A Clinical and Pathological Perspective. Cham, Switzerland: Springer International Publishing; 2016;251-263.
    1. Lin A, Greaves S, Kingston N, Milne D, Ruygrok P. Myocardial calcification after orthotopic heart transplantation. J Heart Lung Transplant. 2014;33(2):219-221.
    1. Fedrigo M, Otero JP, Tona F, Dal Lin C, Crespo-Leiro MG, Bruneval P. Cardiac allograft vasculopathy. In Leone O, Angelini A, Brunavel P, eds. The Pathology of Cardiac Transplantation: A Clinical and Pathological Perspective. Cham, Switzerland: Springer International Publishing; 2016:279-305.
    1. Kransdorf EP, Kobashigawa JA. Genetic and genomic approaches to the detection of heart transplant rejection. Per Med. 2012;9(7):693-705.
    1. Söderlund C, Öhman J, Nilsson J, et al. Acute cellular rejection the first year after heart transplantation and its impact on survival: a single-centre retrospective study at Skåne University Hospital in Lund 1988-2010. Transpl Int. 2014;27(5):482-492.
    1. Raichlin E, Edwards BS, Kremers WK, et al. Acute cellular rejection and the subsequent development of allograft vasculopathy after cardiac transplantation. J Heart Lung Transplant. 2009;28(4):320-327.
    1. Hammond MEH, Revelo MP, Miller DV, et al. ISHLT pathology antibody mediated rejection score correlates with increased risk of cardiovascular mortality: A retrospective validation analysis. J Heart Lung Transplant. 2016;35(3):320-325.
    1. Hammond EH, Yowell RL, Nunoda S, et al. Vascular (humoral) rejection in heart transplantation: pathologic observations and clinical implications. J Heart Transplant. 1989;8(6):430-443.
    1. Forbes RD, Rowan RA, Billingham ME. Endocardial infiltrates in human heart transplants: a serial biopsy analysis comparing four immunosuppression protocols. Hum Pathol. 1990;21(8):850-855.
    1. Marboe CC, Billingham M, Eisen H, et al. Nodular endocardial infiltrates (Quilty lesions) cause significant variability in diagnosis of ISHLT grade 2 and 3A rejection in cardiac allograft recipients. J Heart Lung Transplant. 2005;24(7 Suppl):S219-S226.
    1. Dong C, Winters GL. Enhanced lymphocyte longevity and absence of proliferation and lymphocyte apoptosis in Quilty effects of human heart allografts. Am J Pathol. 1997;151(1):10.
    1. Deng MC, Eisen HJ, Mehra MR, et al. Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. Am J Transplant. 2006;6(1):150-160.
    1. Billingham ME. Endomyocardial biopsy detection of acute rejection in cardiac allograft recipients. Heart Vessels. 1985;1(S1):86-90.
    1. Kottke-Marchant K, Ratliff NB. Endomyocardial lymphocytic infiltrates in cardiac transplant recipients. Incidence and characterization. Arch Pathol Lab Med. 1989;113(6):690-698.
    1. Suit PF, Kottke-Marchant K, Ratliff NB, Pippenger CE, Easely K. Comparison of whole-blood cyclosporine levels and the frequency of endomyocardial lymphocytic infiltrates (the Quilty lesion) in cardiac transplantation. Transplantation. 1989;48(4):618-621.
    1. Pardo-Mindán FJ, Lozano MD. “Quilty effect” in heart transplantation: is it related to acute rejection? J Heart Lung Transplant. 1991;10(6):937-941.
    1. Costanzo-Nordin MR, Winters GL, Fisher SG, et al. Endocardial infiltrates in the transplanted heart: clinical significance emerging from the analysis of 5026 endomyocardial biopsy specimens. J Heart Lung Transplant. 1993;12(5):741-747.
    1. Joshi A, Masek MA, Brown BW, Weiss LM, Billingham ME. “Quilty” revisited: a 10-year perspective. Hum Pathol. 1995;26(5):547-557.
    1. Cho H, Choi J-O, Jeon E-S, Kim J-S. Quilty lesions in the endomyocardial biopsies after heart transplantation. J Pathol Transl Med. 2019;53(1):50-56.
    1. Smith RN, Chang Y, Houser S, Dec GW, Grazette L. Higher frequency of high-grade rejections in cardiac allograft patients after Quilty B lesions or grade 2/4 rejections. Transplantation. 2002;73(12):1928-1932.
    1. Chu KE, Ho EK, de la Torre L, Vasilescu ER, Marboe CC. The relationship of nodular endocardial infiltrates (Quilty lesions) to survival, patient age, anti-HLA antibodies, and coronary artery disease following heart transplantation. Cardiovasc Pathol. 2005;14(4):219-224.
    1. Zakliczynski M, Nozynski J, Konecka-Mrowka D, et al. Quilty effect correlates with biopsy-proven acute cellular rejection but does not predict transplanted heart coronary artery vasculopathy. J Heart Lung Transplant. 2009;28(3):255-259.
    1. Yamani MH, Ratliff NB, Starling RC, et al. Quilty lesions are associated with increased expression of vitronectin receptor (αvβ3) and subsequent development of coronary vasculopathy. J Heart Lung Transplant. 2003;22(6):687-690.
    1. Mengel M, Sis B, Kim D, et al. The molecular phenotype of heart transplant biopsies: relationship to histopathological and clinical variables: the molecular phenotype of heart transplant biopsies. Am J Transplant. 2010;10(9):2105-2115.
    1. Szymanska S, Grajkowska W, Sobieszczanska-Malek M, Zielinski T, Pyzlak M, Pronicki M. Prevalence of the Quilty effect in endomyocardial biopsy of patients after heart transplantation - from cellular rejection to antibody-mediated rejection? Pol J Pathol. 2016;3:216-220.
    1. Van Kaer L, Postoak JL, Wang C, Yang G, Wu L. Innate, innate-like and adaptive lymphocytes in the pathogenesis of MS and EAE. Cell Mol Immunol. 2019;16(6):531-539.
    1. Moro K, Yamada T, Tanabe M, et al. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature. 2010;463(7280):540-544.
    1. Zorn E. New insights on innate B-cell immunity in transplantation. Xenotransplantation. 2018;25(3):e12417.
    1. Zorn E, See SB. Polyreactive natural antibodies in transplantation. Curr Opin Organ Transplant. 2017;22(1):8-13.
    1. Sattar HA, Husain AN, Kim AY, Krausz T. The presence of a CD21+ follicular dendritic cell network distinguishes invasive Quilty lesions from cardiac acute cellular rejection. Am J Surg Pathol. 2006;30(8):1008-1013.
    1. Jonigk D, Lehmann U, Stuht S, et al. Recipient-derived neoangiogenesis of arterioles and lymphatics in Quilty lesions of cardiac allografts. Transplantation. 2007;84(10):1335-1342.
    1. Di Carlo E, D’Antuono T, Contento S, Di Nicola M, Ballone E, Sorrentino C. Quilty effect has the features of lymphoid neogenesis and shares CXCL13?CXCR5 pathway with recurrent acute cardiac rejections. Am J Transplant. 2007;7(1):201-210.
    1. Koenig A, Thaunat O. Lymphoid neogenesis and tertiary lymphoid organs in transplanted organs. Front Immunol. 2016;7:646.
    1. Yin C, Mohanta SK, Srikakulapu P, Weber C, Habenicht AJR. Artery tertiary lymphoid organs: powerhouses of atherosclerosis immunity. Front Immunol. 2016;7:1-15.
    1. Pitzalis C, Jones GW, Bombardieri M, Jones SA. Ectopic lymphoid-like structures in infection, cancer and autoimmunity. Nat Rev Immunol. 2014;14(7):447-462.
    1. Huibers MMH, Gareau AJ, Beerthuijzen JMT, et al. Donor-specific antibodies are produced locally in ectopic lymphoid structures in cardiac allografts. Am J Transplant. 2017;17(1):246-254.
    1. Chatterjee D, Moore C, Gao B, et al. Prevalence of polyreactive innate clones among graft-infiltrating B cells in human cardiac allograft vasculopathy. J Heart Lung Transplant. 2018;37(3):385-393.

Source: PubMed

3
Suscribir