title: Potential impact of microarray diagnosis of T cell-mediated rejection in kidney transplants: The INTERCOM study.
abstract: We previously developed a microarray-based test for T cell-mediated rejection (TCMR) in a reference set of 403 biopsies. To determine the potential impact of this test in clinical practice, we undertook INTERCOM, a prospective international study of 300 indication biopsies from 264 patients (ClinicalTrials.gov NCT01299168). Biopsies from six centers-Baltimore, Barcelona, Edmonton, Hannover, Manchester and Minneapolis-were analyzed by microarrays, assigning TCMR scores by an algorithm developed in the reference set and comparing TCMR scores to local histology assessment. The TCMR score correlated with histologic TCMR lesions-tubulitis and interstitial infiltration. The accuracy for primary histologic diagnoses (0.87) was similar to the reference set (0.89). The TCMR scores reclassified 77/300 biopsies (26%): 16 histologic TCMR were molecularly non-TCMR; 15 histologic non-TCMR were molecularly TCMR, including 6 with polyoma virus nephropathy; and all 46 "borderline" biopsies were reclassified as TCMR (8) or non-TCMR (38). Like the reference set, discrepancies were primarily in situations where histology has known limitations, for example, in biopsies with scarring and inflammation/tubulitis potentially from other diseases. Neither the TCMR score nor histologic TCMR was associated with graft loss. Thus the molecular TCMR score has potential to add new insight, particularly in situations where histology is ambiguous or potentially misleading.
authors.affiliation: Alberta Transplant Applied Genomics Centre, University of Alberta, Edmonton, AB, Canada; Department of Medicine, Division of Nephrology and Transplant Immunology, University of Alberta, Edmonton, AB, Canada.
authors.forename: P F
authors.initials: PF
authors.lastname: Halloran
authors.forename: A B
authors.initials: AB
authors.lastname: Pereira
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: A
authors.initials: A
authors.lastname: Matas
authors.forename: M
authors.initials: M
authors.lastname: Picton
authors.forename: D
authors.initials: D
authors.lastname: De Freitas
authors.forename: J
authors.initials: J
authors.lastname: Bromberg
authors.forename: D
authors.initials: D
authors.lastname: Serón
authors.forename: J
authors.initials: J
authors.lastname: Sellarés
authors.forename: G
authors.initials: G
authors.lastname: Einecke
authors.forename: J
authors.initials: J
authors.lastname: Reeve
mesh_terms: D000906:Antibodies / Q000276:immunology*; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D006801:Humans; D016030:Kidney Transplantation; D025202:Molecular Diagnostic Techniques; D020411:Oligonucleotide Array Sequence Analysis; D011120:Polyomavirus; D027601:Polyomavirus Infections / Q000473:pathology; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D014412:Tumor Virus Infections / Q000473:pathology
chemical_list: D000906:Antibodies
keywords: Classifier; T cell-mediated rejection; kidney transplant; microarrays; molecular diagnostics