Login to Access Video or Poster Abstract: MP06-02
Sources of Funding: This work was supported by JSPS KAKENHI grant number 15K15579 and grant number 25220206. This work was also supported by Japanese Society for Clinical Renal Transplant for an incentive scheme of clinical research grant 2014.

Introduction

ABMR is a diagnostic challenge in living donor kidney transplant (LKTx) medicine, and there is a need to identify predictive markers of ABMR to improve graft survival. The use of serum N-glycans as a predictive biomarker of ABMR has not yet been tested. In the present study, we performed serum N-glycomics in transplant patients and evaluated its potential as a predictive serum-based biomarker of early ABMR.

Methods

N-glycomics in whole serum and immunoglobulins (Igs) fraction were performed in randomly selected 16 recipients with biopsy-proven ABMR occurred within 1 month after LKTx, 40 recipients with biopsy-proven TCMR, and 141 recipients without any adverse events. The putative structure of N-glycans was analyzed by MALDI-TOF-MS analysis.

Results

Serum sialyl hybrid-type N-glycans (m/z 1709, 1871, and 2033) levels before LKTx and on postoperative Day 1 (POD1) was significantly lower in recipients who developed ABMR than non-ABMR group. The m/z 2033 N-glycan <1.3 μM and the presence of preformed donor-specific antibodies (DSA) on POD1 were found to yield a higher odds ratio for prediction of ABMR than did other factors according to logistic regression analysis. Receiver-operating characteristic area under the curve for m/z 2033 < 1.3 μM combined with preformed-DSA status was 0.86. Combined preformed DSA with m/z 2033 N-glycan status; thus, double-positive patients (preformed-DSA positive and m/z 2033 < 1.3 μM) or single-positive patients (preformed-DSA positive or negative and m/z 2033 > 1.3 μM or < 1.3 μM) can cover all 16 ABMR cases. These results suggest that the combined indicator holds promise for identification of patients who will not develop ABMR by means of serum samples collected on POD1. Although, N-glycan profile of immunoglobulin (Ig)s fractions compared with those of whole-serum, ABMR-related N-glycans in Igs fractions were not detected. Therefore, the ABMR-related N-glycans carrying proteins are not an Igs.

Conclusions

The serum m/z 2033 sialyl hybrid-type N-glycan combined with preformed DSA status may predict acute ABMR in patients undergoing LKTx. _x000D_

Funding

This work was supported by JSPS KAKENHI grant number 15K15579 and grant number 25220206. This work was also supported by Japanese Society for Clinical Renal Transplant for an incentive scheme of clinical research grant 2014.