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Molecular and Functional Immune Assays as Non-Invasive Diagnostic Tools to Assess the Risk of Acute Subclinical Rejection After Kidney Transplantation

O. Bestard,1,2 E. Crespo,1 T. Sigdel,2 S. Roedder,2 Y. Ng,2 J. Cruzado,1 M. Lúcia,1 S.-C. Hsieh,1 T. Tran,1 J. Grinyó,1 M. Sarwal.1

1Kidney Transplant Unit, Bellvitge University Hospital, Barcelona, CAT, Spain
2Department of Transplant Surgery, UCSF, San Francisco, CA.

Meeting: 2015 American Transplant Congress

Abstract number: C266

Keywords: Kidney transplantation, Rejection, Renal dysfunction, T cells

Session Information

Session Name: Poster Session C: Translational Biomarkers and Immune Monitoring

Session Type: Poster Session

Date: Monday, May 4, 2015

Session Time: 5:30pm-6:30pm

 Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Subclinical allograft rejection (sc-AR) is still a main cause of allograft loss that can only be assessed through invasive surveillance biopsies. We sought to investigate whether the combination of novel non-invasive biomarkers at the molecular and immune functional level could help identifying patients at risk of sc-AR after kidney transplantation.

Methods:

We combined the assessment of the donor-specific IFN-γ T-cell ELISPOT with a highly sensitive and specific transcriptional biomarker test in peripheral blood samples predicting kidney solid organ clinical rejection (KSORT) using qPCR, in a group of 75 consecutive kidney transplant patients at the time of 6-month protocol biopsies.

Results:

All patients received CNI-based IMS and either rATG or basilimab. 22/75(29%) patients showed histological lesions of sc-AR (18 TCMR, 5 ABMR and 1 mix TCMR/ABMR), 22 showed borderline (BL) lesions and 31 a stable (STA) parenchyma. The KSORT showed a high-risk (HR) and low-risk (LR) scores in 23% and 77% patients, respectively. The T-cell ELISPOT was positive in 41% of patients, whereas negative in 59%. 82% and 70% patients with BL lesions showed a LR KSORT and negative T-cell Elispot, respectively. The KSORT correctly classified as LR 98%) STA and as HR 70% sc-AR (p<0.001), further discriminating as HR all (100%) sc-ABMR and 62.5% sc-TCMR (p<0.001). The d-s T-cell ELISPOT accurately ruled out the presence of sc-TCMR in 72% and predicted its presence in 83.3% (p<0,001), whereas it did not discriminate patients with sc-ABMR (p=NS). transplant recipients with a positive T-cell ELISPOT showed significantly higher tubulitis and interstitium infiltrates than patients with negative a ELISPOT test, whereas those patients with a positive KSORT did show both higher tubulitis (at) and interstium infiltrates (ai) as well as higher glomerulitis (ag) and peritubular capillarities (ptc).

Conclusions:

Combining a non-invasive molecular and functional cellular immune assay allows an accurate identification of patients developing sc-AR, dissecting the main alloimmune effector mechanism responsible of it.

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To cite this abstract in AMA style:

Bestard O, Crespo E, Sigdel T, Roedder S, Ng Y, Cruzado J, Lúcia M, Hsieh S-C, Tran T, Grinyó J, Sarwal M. Molecular and Functional Immune Assays as Non-Invasive Diagnostic Tools to Assess the Risk of Acute Subclinical Rejection After Kidney Transplantation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/molecular-and-functional-immune-assays-as-non-invasive-diagnostic-tools-to-assess-the-risk-of-acute-subclinical-rejection-after-kidney-transplantation/. Accessed May 13, 2025.

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