title: Microarray diagnosis of antibody-mediated rejection in kidney transplant biopsies: an international prospective study (INTERCOM).
abstract: In a reference set of 403 kidney transplant biopsies, we recently developed a microarray-based test that diagnoses antibody-mediated rejection (ABMR) by assigning an ABMR score. To validate the ABMR score and assess its potential impact on practice, we performed the present prospective INTERCOM study (clinicaltrials.gov NCT01299168) in 300 new biopsies (264 patients) from six centers: Baltimore, Barcelona, Edmonton, Hannover, Manchester and Minneapolis. We assigned ABMR scores using the classifier created in the reference set and compared it to conventional assessment as documented in the pathology reports. INTERCOM documented uncertainty in conventional assessment: In 41% of biopsies where ABMR features were noted, the recorded diagnoses did not mention ABMR. The ABMR score correlated with ABMR histologic lesions and donor-specific antibodies, but not with T cell-mediated rejection lesions. The agreement between ABMR scores and conventional assessment was identical to that in the reference set (accuracy 85%). The ABMR score was more strongly associated with failure than conventional assessment, and when the ABMR score and conventional assessment disagreed, only the ABMR score was associated with early progression to failure. INTERCOM confirms the need to reduce uncertainty in the diagnosis of ABMR, and demonstrates the potential of the ABMR score to impact practice.
authors.affiliation: Alberta Transplant Applied Genomics Center, 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: D000293:Adolescent; D015415:Biomarkers / Q000032:analysis*; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007390:International Agencies; D007518:Isoantibodies / Q000276:immunology*; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000401:mortality / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects*; D020411:Oligonucleotide Array Sequence Analysis; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D007518:Isoantibodies
keywords: Antibody-mediated rejection; classifier; kidney transplant; microarrays; molecular diagnostics