Molecular phenotyping of rejection‐related changes in mucosal biopsies from lung transplants
Am J Transplant. 2019; 00: 1– 13
Halloran, K. et al.
Molecular assessment of 3BMBs can detect rejection in a previously unusable biopsy format with potential utility in patients with severe lung dysfunction where TBB is not possible and provide unique insights into airway deterioration. ClinicalTrials.gov NCT02812290.
Molecular assessment of rejection and injury in lung transplant biopsies
J Heart Lung Transplant. 2019 Feb;38(5):504-513.
Kieran M. Halloran, et al.
Molecular assessment of single-piece TBBs can be used to classify lung transplant biopsies and correlated with rejection histology. Two or 3 pieces for each TBB will probably be needed to offset sampling variance.
A molecular biopsy test based on arteriolar under-hyalinosis reflects increased probability of rejection related to under-immunosuppression.
Am J Transplant. 2018 Apr;18(4):821-831.
Einecke G, Reeve J, Halloran PF.
Calcineurin inhibitor immunosuppressive drugs induce changes such as arteriolar hyalinosis (ah) in kidney transplants, raising the possibility that molecular changes in biopsies related to histologic ah can ...
The molecular mechanisms operating in human organ transplant rejection are best inferred from the mRNAs expressed in biopsies because the corresponding proteins often have low expression and short half-lives, while small non-coding RNAs lack specificity...
Our studies in mouse kidney isografts and allografts show that macrophages infiltrate isografts and allografts very early, and that this is accelerated as TCMR emerges. However, on a statistical basis, T-cell molecules are more strongly associated with TCMR...
Gene Expression Profiling for the Identification and Classification of Antibody-Mediated Heart Rejection.
Circulation. 2017 Mar 7;135(10):917-935.
Loupy A, Duong Van Huyen JP, Hidalgo L, Reeve J, Racapé M, Aubert O, Venner JM, Falmuski K, Bories MC, Beuscart T, Guillemain R, François A, Pattier S, Toquet C, Gay A, Rouvier P, Varnous S, Leprince P2, Empana JP, Lefaucheur C, Bruneval P, Jouven X, Halloran PF.
We prospectively monitored 617 heart transplant recipients referred from 4 French transplant centers (January 1, 2006-January 1, 2011) for AMR. We compared patients with AMR (n=55) with a matched control group of 55 patients without AMR.
Intriguingly, rejection associated transcript expression in endomyocardial biopsy specimens to cluster specific molecular patterns into T-cell mediated or antibody-mediated rejection are being studied...
Halloran PF, Potena L, Van Huyen JD, Bruneval P, Leone O, Kim DH, Jouven X, Reeve J, Loupy A.
We analyzed 331 protocol or for-cause EMB specimens from 221 subjects in 3 centers (Edmonton, Bologna, and Paris). Unsupervised principal component analysis (PCA) and archetype analysis used rejection-associated transcripts (RATs) shown in kidney transplants to be associated with antibody-mediated rejection (ABMR) or T cell-mediated rejection (TCMR), or both...
Histologic assessment of kidney transplant biopsies relies on cortex rather than medulla, but for microarray studies, the proportion cortex in a biopsy is typically unknown and could affect the molecular readings...
Comprehensive Analysis of Transcript Changes Associated With Allograft Rejection: Combining Universal and Selective Features.
Am J Transplant. 2017 Jul;17(7):1754-1769
Halloran PF, Venner JM, Famulski KS.
We annotated the top transcripts associated with kidney transplant rejection by p-value, either universal for all rejection or selective for T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR; ClinicalTrials.gov NCT01299168)...
Assessing rejection-related disease in kidney transplant biopsies based on archetypal analysis of molecular phenotypes.
JCI Insight. 2017 Jun 15;2(12).
Reeve J, Böhmig GA, Eskandary F, Einecke G, Lefaucheur C, Loupy A, Halloran PF; MMDx-Kidney study group.
Microarray data from 1,208 kidney transplant biopsies were collected prospectively from 13 centers. Cross-validated classifier scores predicting the presence of antibody-mediated
rejection (ABMR), T cell–mediated rejection (TCMR), and 5 related histologic lesions were generated using supervised machine learning methods ...
Molecular assessment of disease states in kidney transplant biopsy samples.
Nat Rev Nephrol. 2016 Sep;12(9):534-48
Halloran PF, Famulski KS, Reeve J.
Study of the relationship between gene expression and clinical phenotypes in kidney transplant biopsy samples has led to the development of a system that enables diagnoses of specific disease states on the basis of messenger RNA levels in the biopsy sample...
Expression microarrays from 681 kidney transplant indication biopsies taken either early (n = 282, <1 year) or late (n = 399, >1 year) after transplant were used to analyze the molecular landscape of fibrosis in relationship to histologic fibrosis and diseases...
Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated Rejection in Late Kidney Transplant Recipients.
Am Soc Nephrol. 2015 Jul;26(7):1711-20.
Halloran PF, Chang J, Famulski K, Hidalgo LG, Salazar ID, Merino Lopez M, Matas A, Picton M, de Freitas D, Bromberg J, Serón D, Sellarés J, Einecke G, Reeve J.
The prevalent renal transplant population presents an opportunity to observe the adaptive changes in the alloimmune response over time, but such studies have been limited by uncertainties in the conventional biopsy diagnosis of T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR)...
We used microarray analysis of kidney transplant biopsies to identify the changes in pure ABMR. We found that the ABMR transcript changes in the initial Discovery Set were strongly conserved in a subsequent Validation Set...