Purpose: Antibody-mediated rejection (ABMR) has been recognized as a major cause of graft loss. Early diagnosis and effective treatment are crucial for salvaging grafts undergoing ABMR. Detecting the blood expression of genes involved in IFN signaling might offer a non-invasive way to differentiate ABMR from patients with stable graft function (SGF), urinary tract infection (UTI), T cell-mediated rejection (TCMR) and interstitial fibrosis/tubular atrophy (IFTA).

Methods: A total of 187 adult kidney transplantation recipients were recruited including ABMR (n=20), SGF (n=50), UTI (n=17), Borderline (BL) (n=24), TCMR I (n=19), TCMR II/III (n=27) and IFTA (n=30) patients. Total RNA was isolated from whole blood of patients at the time of biopsy. Quantitative real-time PCR was performed to measure the expression level of genes involved in IFN signaling. The expression levels of different patient groups were compared with each other by Mann-Whitney U test. Receiver operating characteristics (ROC) analysis was performed to evaluate the diagnostic value for distinguishing ABMR patients from others.

Results: mRNA expression levels of 6 genes involved in IFN signaling were significantly up-regulated in blood of ABMR patients compared to the SGF group (P<0.0040). One of the candidates' gene expression level in ABMR was significantly higher than in the SGF, BL, TCMR II/III groups and significantly lower in the UTI group (P<0.0080). The area under curve (AUC) of ROC distinguishing ABMR from all other groups is 0.6924 (95%CI: 0.6070, 0.7778)(p=0.0050) with a sensitivity of 0.9500 and a specificity of 0.5152, AUC of ROC distinguishing ABMR from the SGF group is 0.8430 (95%CI: 0.7516, 0.9344)(P<0.0001) with a sensitivity of 0.9500 and a specificity of 0.7200. Additionally to the mRNA expression, candidates were also measured on protein level in plasma.

Conclusions: The expression measurement of genes involved in IFN signaling might offer a better diagnosis of ABMR distinguishing it from other complications like TCMR, UTI and IFTA after kidney transplantation.

CITATION INFORMATION: Matz M., Zhang Q., Heinrich F., Lorkowski C., Wu K., Durek P., Lachmann N., Mashreghi M-.F., Budde K. Diagnosis of Antibody-Mediated Rejection after Kidney Transplantation by Blood Expression of Genes Involved in IFN Signaling Am J Transplant. 2017;17 (suppl 3).

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