Microarray Diagnosis of Antibody‐Mediated Rejection in Kidney Transplant Biopsies: An International Prospective Study (INTERCOM)

• Published in: American journal of transplantation Vol. 13; no. 11; pp. 2865 - 2874
• Main Authors: Halloran, P. F., Pereira, A. B., Chang, J., Matas, A., Picton, M., De Freitas, D., Bromberg, J., Serón, D., Sellarés, J., Einecke, G., Reeve, J.
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley 01.11.2013; Elsevier Limited
• Subjects: Adolescent; Antibodies; Antibody‐mediated rejection; Biological and medical sciences; Biomarkers - analysis; classifier; Follow-Up Studies; Gene Expression Profiling; Graft Rejection - diagnosis; Graft Rejection - immunology; Graft Survival - immunology; Humans; International Agencies; Isoantibodies - immunology; Kidney Failure, Chronic - immunology; Kidney Failure, Chronic - mortality; Kidney Failure, Chronic - surgery; kidney transplant; Kidney Transplantation - adverse effects; Medical sciences; microarrays; molecular diagnostics; Oligonucleotide Array Sequence Analysis; Postoperative Complications; Prognosis; Prospective Studies; Risk Factors; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Survival Rate; World; Graft(material); molecular diagnostics; Molecular diagnostic; Antibody; kidney transplant; Transplantation; Homotransplantation; Antibody-mediated rejection; Kidney; microarrays; Prospective; Rejection; Anatomic pathology; Treatment; Urinary system; Biopsy; Surgery; classifier; Graft; International
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/ajt.12465

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. The authors report that when the molecular antibody‐mediated rejection score derived in a reference set of kidney transplant biopsies was tested in 300 new biopsies (the INTERCOM study), it validated the value of molecular testing for establishing not only diagnosis but also prognosis, and documented the difficulties centers have in making this diagnosis by conventional means.