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MMDx Procedure

Learn how to collect your biopsy sample, prepare, and ship it for analysis.

Molecular phenotypes of liver transplant injury: the INTERLIVER study

ATC2020 Presentation by KS Madill-Thomsen, PF Halloran, and the INTERLIVER Study Group

Cross-organ comparisons: Temporal Gene Expression Changes In Kidney, Heart, Liver, and Lung Transplant Biopsies

ATC2020 Presentation by PF Halloran, J Reeve, and the INTERLIVER, INTERLUNG, INTERCOMEX, INTERHEART Study Groups

The molecular phenotype of kidney injury: relationship to function and survival.

AST2020 Presentation by PF Halloran, J Reeve, and the INTERCOMEX Study Group

Molecular diagnosis of rejection in liver transplant biopsies: the INTERLIVER study

AST 2020 ePoster presentation by Madill-Thomsen, KS., Halloran, PF., and the INTERLIVER Study Group

Lung mucosal biopsies deteriorate with time post transplant: A molecular analysis

AST 2020 ePoster presentation by Parkes, MD., et al.

Evolution of molecular lung transplant biopsy assessment: rejection can be detected in mucosal as well as transbronchial biopsies

AST 2020 ePoster presentation by Parkes, MD., et al.

Calibration of Natera circulating donor-derived cfDNA against Molecular Microscope® Diagnostic System (MMDx) results in indication biopsies

AST 2020 presentation by Philip F. Halloran

Molecular profiles of injury in heart transplant allograft: Relationship to rejection, ejection fraction, and survival.

AST 2020 presentation by PF Halloran, J Reeve and the INTERHEART Study Group

Personalized Transplant Care Through Precision Medicine

Heart and Lung

Reading Human Biopsies using mRNA Expression

Includes a summary of the clinical trials.

Publications: 2015 - Present
Factors associated with kidney graft survival in pure antibody-mediated rejection at the time of indication biopsy: Importance of parenchymal injury but not disease activity

Am J Transplant. 2020;10.1111/ajt.16161

Einecke1, G., et al.

We studied the relative association of clinical, histologic, and molecular variables with risk of kidney transplant failure after an indication biopsy, both in all kidneys and in kidneys with pure antibody-mediated rejection (ABMR).

Analysis of RNA Transcripts by the Molecular Microscope Diagnostic System (MMDx) Can Direct Management after Indication Kidney Transplant Biopsy

J Clinical Nephrology & Kidney Diseases

Lawrence, C. et al.

We report two cases of graft dysfunction in which the clinical decision making was potentiated by the Molecular Microscope® Diagnostic System (MMDx), both at indication and follow up biopsy.

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. 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 ...

Review: The transcripts associated with organ allograft rejection.

J Transplant. 2018 Apr;18(4):785-795.

Halloran PF, Venner JM, Madill-Thomsen KS, Einecke G, Parkes MD, Hidalgo LG, Famulski KS.

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...

Response by Loupy et al to Letters Regarding Article, "Gene Expression Profiling for the Identification and Classification of Antibody-Mediated Heart Rejection".

Circulation. 2017 Aug 15;136(7):698-699.

Loupy A, Hidalgo L, Duong JP, Bruneval P, Jouven X, Halloran PF.

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.

Heart transplantation at 50

Lancet. 2017 Dec 2;390(10111):e43-e45

Mandeep R Mehra

​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...

Building a tissue-based molecular diagnostic system in heart transplant rejection: The heart Molecular Microscope Diagnostic (MMDx) System.

J Heart Lung Transplant. 2017 Nov;36(11):1192-1200.

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...

Real Time Central Assessment of Kidney Transplant Indication Biopsies by Microarrays: The INTERCOMEX Study.

Am J Transplant. 2017 Nov;17(11):2851-2862

Halloran PF, et al.

The authors conducted a prospective trial to assess the feasibility of real time central molecular assessment of kidney transplant biopsy samples from 10 North American or European centers...

The Effect of Cortex/Medulla Proportions on Molecular Diagnoses in Kidney Transplant Biopsies: Rejection and Injury Can Be Assessed in Medulla.

Am J Transplant. 2017 Aug;17(8):2117-2128.

Madill-Thomsen KS, Wiggins RC, Eskandary F, Böhmig GA, Halloran PF.

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; 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 ...

Hyalinosis Lesions in Renal Transplant Biopsies: Time-Dependent Complexity of Interpretation.

Am J Transplant. 2017 May;17(5):1346-1357

Einecke G, Reeve J, Halloran PF.

Because calcineurin inhibitor (CNI) immunosuppressive drugs induce arteriolar hyalinosis (ah) in kidney transplants, ah lesions can potentially provide information about drug exposure...

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...

Identifying Subphenotypes of Antibody-Mediated Rejection in Kidney Transplants.

Am J Transplant. 2016 Mar;16(3):908-20

Halloran PF, Merino Lopez M, Barreto Pereira A

The key lesions in antibody-mediated kidney transplant rejection (ABMR) are microcirculation inflammation (peritubular capillaritis and/or glomerulitis lesions, abbreviated "pg") and glomerular double contours (cg lesions)...

Relationships among injury, fibrosis, and time in human kidney transplants

JCI Insight. 2016 Jan 21;1(1)

Venner JM, Famulski KS, Reeve J, Chang J, Halloran PF.

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)...

The molecular landscape of antibody-mediated kidney transplant rejection: evidence for NK involvement through CD16a Fc receptors.

Am J Transplant. 2015 May;15(5):1336-48

Venner JM, Hidalgo LG, Famulski KS, Chang J, Halloran PF.

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...

Publications: 2014 - Prior
Fundamental Concepts Regarding Graft Injury and Regeneration: Tissue Injury, Tissue Quality, and Recipient Factors

Textbook of Organ Transplantation Set,. 2014 Jul;10:99-118

Kreepala C, Famulski KS, Halloran PF.

Antibody-mediated rejection, T cell-mediated rejection, and the injury-repair response: new insights from the Genome Canada studies of kidney transplant biopsies.

Kidney Int. 2014 Feb;85(2):258-64

Halloran PF, Reeve JP, Pereira AB, Hidalgo LG, Famulski KS.

Molecular landscape of T cell-mediated rejection in human kidney transplants: prominence of CTLA4 and PD ligands.

Am J Transplant. 2014 Nov;14(11):2565-76

Venner JM, Famulski KS, Badr D, Hidalgo LG, Chang J, Halloran PF.

Molecular diagnosis of T cell-mediated rejection in human kidney transplant biopsies.

Am J Transplant. 2013 Mar;13(3):645-55

Reeve J, Sellarés J, Mengel M, Sis B, Skene A, Hidalgo L, de Freitas DG, Famulski KS, Halloran PF.

Molecular phenotypes of acute kidney injury in kidney transplants.

J Am Soc Nephrol. 2012 May;23(5):948-58

Famulski KS, de Freitas DG, Kreepala C, Chang J, Sellares J, Sis B, Einecke G, Mengel M, Reeve J, Halloran PF.

Concordance among pathologists in the second Cardiac Allograft Rejection Gene Expression Observational Study (CARGO II).

Transplantation. 2012 Dec 15;94(11):1172-7

Crespo-Leiro MG, et al.

Pathologic interpretation of transbronchial biopsy for acute rejection of lung allograft is highly variable.

Am J Transplant. 2011 Feb;11(2):320-8

Arcasoy SM, Berry G, Marboe CC, Tazelaar HD, Zamora MR, Wolters HJ, Fang KC, Keshavjee S.

The molecular phenotype of heart transplant biopsies: relationship to histopathological and clinical variables.

Am J Transplant. 2010 Sep;10(9):2105-15

Mengel M, Sis B, Kim D, Chang J, Famulski KS, Hidalgo LG, Einecke G, de Freitas DG, Tymchak W, Burton J, Halloran PF.

Early loss of renal transcripts in kidney allografts: relationship to the development of histologic lesions and alloimmune effector mechanisms.

Am J Transplant. 2007 May;7(5):1121-30.

Einecke G, Broderick G, Sis B, Halloran PF.

Microarray analysis of rejection in human kidney transplants using pathogenesis-based transcript sets.

Am J Transplant. 2007 Dec;7(12):2712-22.

Mueller TF, Einecke G, Reeve J, Sis B, Mengel M, Jhangri GS, Bunnag S, Cruz J, Wishart D, Meng C, Broderick G, Kaplan B, Halloran PF.

Transcriptome analysis reveals heterogeneity in the injury response of kidney transplants.

Am J Transplant. 2007 Nov;7(11):2483-95.

Famulski KS, Broderick G, Einecke G, Hay K, Cruz J, Sis B, Mengel M, Halloran PF.

Changes in the transcriptome in allograft rejection: IFN-gamma-induced transcripts in mouse kidney allografts.

Am J Transplant. 2006 Jun;6(6):1342-54.

Famulski KS, Einecke G, Reeve J, Ramassar V, Allanach K, Mueller T, Hidalgo LG, Zhu LF, Halloran PF.

Expression of CTL associated transcripts precedes the development of tubulitis in T-cell mediated kidney graft rejection.

Am J Transplant. 2005 Aug;5(8):1827-36.

Einecke G, Melk A, Ramassar V, Zhu LF, Bleackley RC, Famulski KS, Halloran PF.