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Dong, Kyu, Yu, Seok, Kim, Sohn, Hyun, Soon, Kim, and Myoung: Predictive Value of Donor Specific Antibody Measured by Luminex Single Antigen Assay for Antibody Mediated Rejection after Kidney Transplantation
Original Article

J Korean Soc Transplant 2011;25(3):169-175.

Published online: 10 September 2011

DOI: https://doi.org/10.4285/jkstn.2011.25.3.169

Predictive Value of Donor Specific Antibody Measured by Luminex Single Antigen Assay for Antibody Mediated Rejection after Kidney Transplantation

Jin Joo Dong, M.D.1, 2, Ha Huh Kyu, M.D.1, 2, Seun Kim Yu, M.D.1, 2, Jun Yoon Seok, M.D.1, Hae-Jin Kim, B.S.2, Seung-sook Sohn, B.S.2, Jung Kim Hyun, R.N.2, II Kim Soon, M.D.1, 2, Hyon-Suk Kim, M.D.3, Soo Kim Myoung, M.D.1, 2

1Department of Surgery, Research Institute for Transplantation Korea

2Department of Laboratory Medicine Korea

3Yonsei University College of Medicine, Seoul Korea

책임저자：김명수, 서울시 서대문구 신촌동 134연세대학교 의과대학 외과학교실, 120-752 Tel: 02-2228-2123, Fax: 02-313-8289 E-mail: ysms91@yuhs.ac

Received 20 May 2011       Revised 17 July 2011       Accepted 21 July 2011

Copyright © 2011 The Korean Society for Transplantation

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Luminex panel reactive antibody (PRA) is a method that is well known for its high sensitivity and specificity. By using a single antigen assay, the presence or absence of donor specific antibody (DSA) can be determined and its strength can be quantified in terms of the mean fluorescence intensity (MFI). In this study, we analyzed the correlation between the pre-transplant PRA and DSA measured by the Luminex method and the post-transplant clinical features after kidney transplantation.

Methods

A total of 123 pre-transplant sera samples from kidney transplanted patients were tested. Luminex-PRA identification tests were performed using a Luminex fluoroanalyzer and a LifeCodes class I, II ID Kits. Single antigen assay by the Luminex method was used for detecting DSA and its MFI.

Results

The positive Luminex-PRA group included more highly-sensitized patients such as women, patients with a previously positive lymphocyte cross match test and patients who were undergoing retransplantation. There was no correlation between the acute rejection rate and positive PRA on the Luminex-PRA. However, pretransplant DSA detected by the single antigen assay was significantly associated with episodes of antibody mediated rejection (P=0.047, OR=10.2), and DSA with higher MFI values (MFI≥3,000) was associated with antibody mediated rejection (P=0.023).

Conclusions

Although pre-transplant positive PRA was not correlated with acute rejection episodes, the DSA measured by the Luminex single antigen assay seems to have a predictive value for post-transplant antibody mediated rejection.

Keywords: Histocompatibility antigen, Kidney transplantation, Rejection

References

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Fig. 1.
Graft survival rate according to pre-transplant panel reactive antibody (PRA) and donor specific antibody (DSA). Abbreviations: PRA, panel reactive antibody measured by Luminex-PRA test; DSA, donor specific antibody measured by Luminex-Single antigen PRA test.
jkstn-25-169f1.tif
Fig. 2.
Post-transplant change of graft function measured by estimated glomerular filtration rate (eGFR, by MDRD formula) according to the pre-transplant panel reactive antibody (PRA) and donor specific antibody (DSA) status. Abbreviations: PRA, panel reactive antibody measured by Luminex-PRA test; DSA, donor specific antibody measured by Luminex-Single antigen PRA test. *P＜0.05.
jkstn-25-169f2.tif
Table 1.
Association between clinical factors related with HLA alloimmunization and panel reactive antibody (PRA) results by Luminex method
Clinical factors Luminex-PRA ID P-value
I (－) and II (－) (n=78) I or II (+) (n=27) I (+) and II (+) (n=18)
Sex       ＜0.0001
Female recipients (n=42) 18 (42.9%) 11 (26.2%) 13 (31.0%)  
Male recipients (n=81) 60 (74.1%) 16 (19.8%) 5 (6.2%)  
Previous LCM results       ＜0.0001
Positive history (n=14) 5 (35.7%) 1 (7.1%) 8 (57.1%)  
Negative (n=109) 73 (67.0%) 26 (23.9%) 10 (9.2%)  
Previous transplantation history       0.034
Positive (n=14) 8 (57.1%) 1 (7.1%) 5 (35.7%)  
Negative (n=109) 70 (64.2%) 26 (23.9%) 13 (11.9%)  

Abbreviations: I, class I; II, class II; LCM, lymphocyte cross match.

(－) PRA ID ＜10%, (+) PRA ID ≥10%.

Table 2.
Association between acute rejection episodes and panel reactive antibody (PRA) results by Luminex method
Clinical factors Luminex-PRA ID P-value∗
I (－) and II (－) (n=78) I or II (+) (n=27) I (+) and II (+) (n=18)
Rejection-free (n=98) 64 (65.3%) 21 (21.4%) 13 (13.3%)  
Clinical rejection∗ (n=9) 4 (44.4%) 2 (22.2%) 3 (33.3%) 0.201
Pathologic rejection, cell-mediated (n=11) 7 (63.6%) 4 (36.4%) 0 (－) 0.340
Pathologic rejection, antibody-mediated (n=5) 3 (60.0%) 0 (－) 2 (40.0%) 0.237
Abbreviations: I, class I; II, class II.

∗ P-value compared with non-rejection group;

† Clinical rejection: clinically diagnosed (not biopsy-proven).

(－) PRA ID ＜10%, (+) PRA ID ≥10%

Table 3.
Association between acute rejection episodes and pre-transplant donor specific antibody (DSA) status
Clinical factors DSA (－)(n=112) DSA (+)(n=11) P-value∗
Rejection-free (n=98) 92 (93.9%) 6 (6.1%)  
Clinical rejection† (n=9) 7 (77.8%) 2 (22.2%) 0.135
Pathologic rejection, 10 (90.9%) 1 (9.1%) 0.536
cell-mediated (n=11)      
Pathologic rejection, 3 (60.0%) 2 (40.0%) 0.047‡
antibody-mediated (n=5)      

Abbreviation: DSA, donor specific antibody measured by Lumi-nex-single antigen assay.

∗ P-value compared with rejection-free group;

† Clinical rejection: clinically diagnosed (not biopsy-proven);

‡ OR: 10.2, 95% CI: 1.4–73.3.

Table 4.
Association between acute rejection episodes and strength (MFI values) of donor specific antibody which was measured by single antigen assay
Clinical factors DSA(－) by SA-PRA DSA (+) by SA-PRA P-value*
MFI＜3000 MFI＞=3,000
Total number 112 6 5  
Rejection-free (n=98) 92 (93.9%) 3 (3.1%) 3 (3.1%)  
Clinical rejection† (n=9) 7 (77.8%) 2 (22.2%) 0 (－) 0.073
Pathologic rejection, cell-mediated (n=11) 10 (90.9%) 1 (9.1%) 0 (－) 0.536
Pathologic rejection, antibody-mediated (n=5) 3 (60.0%) 0 (－) 2 (40.0%) 0.023

Abbreviation: MFI, mean fluorescence intensity.

*P-value compared with rejection-free group; † Clinical rejection: clinically diagnosed (not biopsy-proven).

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