Report of the 2022 Banff Heart Concurrent: Focus on non-human leukocyte antigen antibodies in rejection and the pathology of “mixed” rejection

Fedrigo, Marny; Berry, Gerald J.; Coutance, Guillaume; Reed, Elaine F.; Lin, Chieh-Yu; Giarraputo, Alessia; Kransdorf, Evan; Thaunat, Olivier; Goddard, Martin; Angelini, Annalisa; Neil, Desley A.H.; Bruneval, Patrick; Duong Van Huyen, Jean-Paul; Loupy, Alexandre; Miller, Dylan V.

doi:10.1016/j.ajt.2023.10.004

Cited by 3 publications

(2 citation statements)

References 43 publications

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“…In contrast, fibrosis according to both Ishak F and LAF scores was highest in cABMR, which also had, by definition, the highest frequency of DSA. Fifty-six percent of biopsies with cABMR also had features of TCMR with an RAI ≥1+1+1, similar as in ABMR after other solid organ transplantation (SOT) 34,35 . Usage of cyclosporine A (CsA) and tacrolimus (TAC) as primary immunosuppressive drug was different between the groups (p=0.022 and p=0.006 respectively; Table 1).…”

Section: Characterization Of the Training Cohortmentioning

confidence: 71%

Molecular signatures of chronic antibody-mediated rejection in human liver transplants

Engel,

Alaswad,

Campos-Murguia

et al. 2024

Preprint

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Background&Aims: The role of antibody-mediated rejection (ABMR) after liver transplantation (LT) remains controversial. Chronic ABMR (cABMR) is often subclinical and potentially missed without surveillance biopsies (svLbx) which are not established in most LT centers. Transcriptome analysis previously characterized molecular changes in T cell-mediated rejection (TCMR) after solid organ transplantation. We aimed to identify molecular cABMR signatures after LT for a more comprehensive understanding of cABMR. Methods: We retrospectively identified indication and svLbx from our prospective institutional biorepository (n=1207 over 12 years). We performed RNA-sequencing on liver biopsies (discovery cohort: n=71; validation cohort: n=58). Downstream analyses explored the unique and common molecular features of cABMR, clinical (clinTCMR) and subclinical TCMR (subTCMR) compared to no histological rejection (NHR). Results: Nineteen percent of LT recipients with donor-specific antibodies had cABMR. Eighty-one percent of patients with cABMR had ALT and AST ≤2x the upper limit of normal, only being recognized by svLbx. The cABMR group displayed differentially expressed genes (DEGs) uniquely enriched in fibrogenesis-, complement activation- and TNFα-signaling-related pathways. ClinTCMR showed DEGs uniquely enriched in antigen presentation-, interferon-signaling-, and T cell receptor-signaling-related pathways. Common cABMR and clinTCMR DEGs were enriched in chemokine-signaling- and cytokine response-related pathways. Gene set enrichment scores of interferon-signaling and extracellular matrix remodeling pathways discriminated cABMR and clinTCMR. Molecular signatures of clinTCMR correlated with histological TCMR-patterns. Molecular cABMR-signatures correlated with lobular graft injury and liver fibrosis scores. The validation cohort consistently showed patterns of DEGs associating cABMR with fibrogenesis- and NF-κB-signaling-related pathways and clinTCMR with interferon-signaling- and adaptive immunity-related pathways. SubTCMR was molecularly almost indistinguishable from NHR. Conclusions: We report transcriptome-unique features of cABMR that is a unique molecular identity associated with inflammation and fibrogenesis.

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Section: Characterization Of the Training Cohortmentioning

confidence: 71%

Molecular signatures of chronic antibody-mediated rejection in human liver transplants

Engel,

Alaswad,

Campos-Murguia

et al. 2024

Preprint

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“…One of the exciting new undertakings in 2023–2024 has been to allow a period of public comment on the draft papers from the 2022 Banff meeting 58 . This meant that the papers from the meeting 59–65 underwent much more widespread discussion worldwide and more diverse input than was the case with the papers from previous Banff transplant pathology meetings.…”

Section: Whereto? On To a Bright Futurementioning

confidence: 99%

Transplant nephropathology: Wherefrom, wherein, and whereto

Solez,

Eknoyan

2024

Clinical Transplantation

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Renal pathology is a relatively recent entry in nephrology. While diseases of the kidney are old, their study began in the 19th century with the report of Richard Bright of the lesions of end‐stage kidney disease. Its easy diagnosis from albuminuria soon elevated Bright's nephritis into a leading cause of death. The transformative events in the care of these cases were renal replacement therapy that converted a fatal into a chronic disease, and kidney biopsy that allowed study of the course and pathogenesis of kidney disease. Apart from its fundamental contributions to clinical nephrology, biopsy of renal allografts became an integral component of the evaluation and care of kidney transplant recipients. The Banff transplant pathology conferences launched in 1991 led to developing the classification of allograft pathology into an essential element in the evaluation, treatment, and care of allograft recipients with spirit of discovery. That success came at the cost of increasing complexity leading to the recent realization that it may need the refinement of its consensus‐based system into a more evidence‐based system with graded statements that are easily accessible to the other disciplines involved in the care of transplanted patients. Collaboration with other medical disciplines, allowing public comment on meeting reports, and incorporation of generative artificial intelligence (AI) are important elements of a successful future. The increased pace of innovation brought about by AI will likely allow us to solve the organ shortage soon and require new classifications for xenotransplantation pathology, tissue engineering pathology, and bioartificial organ pathology.

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Outcome-based Risk Assessment of Non-HLA Antibodies in Heart Transplantation: A Systematic Review

Panicker,

Prokop,

Hacke

et al. 2024

The Journal of Heart and Lung Transplantation

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Report of the 2022 Banff Heart Concurrent: Focus on non-human leukocyte antigen antibodies in rejection and the pathology of “mixed” rejection

Cited by 3 publications

References 43 publications

Molecular signatures of chronic antibody-mediated rejection in human liver transplants

Molecular signatures of chronic antibody-mediated rejection in human liver transplants

Transplant nephropathology: Wherefrom, wherein, and whereto

Outcome-based Risk Assessment of Non-HLA Antibodies in Heart Transplantation: A Systematic Review

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