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Journal List > Korean J Transplant > v.33(3) > 1134768

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Park, Park, Joo, Huh, Kim, Kim, Kim, and Kim: Clinical significance of donor-specific anti-HLA-DR51/52/53 antibodies for antibody-mediated rejection in kidney transplant recipients
Original Article

Korean J Transplant 2019;33(3):47-54.

Published online: 30 September 2019

DOI: https://doi.org/10.4285/jkstn.2019.33.3.47

Clinical significance of donor-specific anti-HLA-DR51/52/53 antibodies for antibody-mediated rejection in kidney transplant recipients

Borae Geum Park1, 2, Younhee Park1, Dong Jin Joo3, Kyu Ha Huh3, Myoung Soo Kim3, Soon Il Kim3, Yu Seun Kim3, Hyon-Suk Kim1

1Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

2Department of Laboratory Medicine, Korea University Guro Hospital, Seoul, Korea

3Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

Correspondence to: Hyon-Suk Kim Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea Tel: +82-2-2228-2443, Fax: +82-2-364-1583 E-mail: kimhs54@yuhs.ac

Received 14 March 2019       Revised 12 August 2019       Accepted 13 August 2019

Copyright © 2019 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/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

The presence of donor-specific antibodies (DSAs) to human leukocyte antigen (HLA) increases the risk of antibody-mediated rejection (ABMR) after kidney transplantation (KT). However, the clinical relevance of anti-HLA-DR51/52/53 antibodies remains unclear because of their weak antigen expression. This study evaluated the association between anti-HLA-DR51/52/53 DSAs and ABMR.

Methods

We retrospectively reviewed the single-antigen-bead panel reactive antibody (single PRA) results of 130 patients tested between August 1, 2009 and March 6, 2015, based on clinical necessity after allograft KT. Single PRA analysis was performed using Luminex assay kits (Lifecodes LSA class I and II). We reviewed the clinical course and biopsy results of patients with anti-HLA-DR51/52/53 DSAs.

Results

Post-KT DSAs were identified in 89 of the 130 patients (68.5%), with 26 of 32 class I DSAs and 63 of 66 class II DSAs being immunodominant DSAs. Thirteen patients had anti-HLA-DR51/52/53 DSAs. Three patients with anti-HLA-DR51/52/53 immunodominant DSAs alone were diagnosed with biopsy-proven ABMR. One patient who developed anti-HLA-DR DSA 13 days after KT showed a rapid increase in anti-HLA-DR51 DSA and had biopsy-proven ABMR.

Conclusions

Although the expression of the HLA-DR51/52/53 antigen was weak, anti-HLA-DR51/52/53 DSAs might be correlated with biopsy-proven ABMR. Therefore, anti-HLA-DR51/52/53 DSAs must be evaluated as a cause of ABMR after transplantation.

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Keywords: Donor specific antibody, Antibody mediated rejection, Human leukocyte antigen

jkstn-2019-33-3-47f1.tif
Fig. 1.
Pathologic results according to immunodominant donor-specific antibody (DSA). A total of 70 biopsy results could be obtained at the time of DSA detection. HLA, human leukocyte antigen; g, glomerulitis; ptc, peritubular capillaritis.

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Table 1.
Linked genes between HLA-DRB1 and -DRB3/4/5
Gene Coding protein Linked HLA DR antigen
DRB3 Beta chain of DR52 DR11, DR12, DR13, DR14, DR17(3), DR18(3)
DRB4 Beta chain of DR53 DR4, DR7, DR9
DRB5 Beta chain of DR51 DR15(2), DR16(2)
None None DR1, DR8, DR10

HLA, human leukocyte antigen.

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Table 2.
Distribution of the DSA with highest MFI level (immunodominant DSA) detected in 130 patients with elevated serum creatinine levels after kidney transplantation
Immunodominant DSA Number of patients (%) MFI range Median follow–up day (range)
Class I 26 (20.0)
  Anti-HLA-A 9 (6.9) 1,653–17,249 2,811 (1,682–7,579)
  Anti-HLA-A DSA alone 8 (6.2)
Anti-HLA-A with class II DSA 1 (0.7)
Anti-HLA-B 14 (10.8) 1,328–4,790 3,003 (68–8,542)
Anti-HLA-B DSA alone 12 (9.2)
Anti-HLA-B with class II DSA 2 (1.5)
Anti-HLA-C 3 (2.3) 1,755–4,656 1,109 (970–6,256)
Class II 63 (48.5)
Anti-HLA-DR 23 (17.7) 1,543–16,203 2,834 (13–7,943)
Anti-HLA-DR DSA without class I DSA 19 (14.6)
Anti-HLA-DR DSA with class I DSA 4 (3.1)
Anti-HLA-DRB1 DSA with anti-HLA-DR51/52/53 DSA 10 (7.7)
Anti-HLA-DRB1 DSA alone with or without class I DSA 10 (7.7)
Anti-HLA-DR51/52/53 DSA alone with or without class I DSA 3 (2.3)
Anti-HLA-DQ 40 (30.8) 1,105–20,611 1,739 (33–7,252)
Anti-HLA-DQ DSA alone 30 (23.1)
Anti-HLA-DQ DSA with anti-HLA-DR DSA 8 (6.2)
Anti-HLA-DQ DSA with class I DSA 2 (1.5)
No DSA 41 (31.5) 2,346 (66–9,019)

DSA, donor-specific antibody; MFI, mean fluorescence intensity; HLA, human leukocyte antigen.

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Table 3.
Clinical data and biopsy results of 10 patients who developed both anti-HLA-DR 51/52/53 DSA and anti-HLA-DRB1 DSA
HLA-DR typing
 DSA to HLA-DRB1 or class I (MFI) DSA to HLA-DRB3/4/5 (MFI) Day after transplantation Kidney biopsy
Recipient Donor
DR11, DR13, DR52, DR52 DR4, DR11, DR53, DR52 DR4 (2,802) DR53 (1,252) 325 Transplant glomerulopathy, C4d(–), g0, ptc0
DR10, DR15, DR51 DR13, DR15, DR52, DR51 DR13 (12,654), A24 (2,599) DR52 (13,131) 1,361 ABMR, C4d(+, diffuse), g2, ptc1
DR4, -, DR53 DR4, DR13, DR53, DR52 DR13 (13,859) DR52 (5,252) 990 ABMR, C4d(–), g3, ptc0
DR15, DR4, DR51, DR53 DR15, DR13, DR51, DR52 DR13 (15,190) DR52 (14,878) 2,671 TCMR, type 1B, ABMR, C4d(–), g1, ptc0
DR4, DR14, DR53, DR52 DR4, DR15, DR53, DR51 DR15 (10,736), DR51 (15,615) 257 TCMR, type 2B, ABMR, grade II, C4d(+, diffuse) g0, ptc2
DR4, DR13, DR53, DR52 DR15, DR13, DR51, DR52 A24 (2,344) DR15 (6,763)a) DR51 (12,850) 13 ABMR, C4d(+, diffuse), g0, ptc1
DR13, -DR52 DR7, DR13, DR53, DR52 DR7 (10,616) DR53 (11,322) 3,622 ABMR, grade II, C4d(–), g0, ptc3
DR8,- DR8, DR13, DR52 DR13 (11,372) DR52 (14,261) 3,409 ABMR, grade II, C4d(+, diffuse), g1, ptc2
DR10, DR11, DR52 DR9, DR10, DR53 DR9 (15,822) DR53 (2,692) 2,996 ABMR, grade II, C4d(+, diffuse), g1, ptc0
DR1, DR4, DR53 DR1, DR13, DR52 DR13 (16,203) DR52 (2,711) 3,417 ABMR, grade II, C4d(+, diffuse), g0, ptc2

HLA, human leukocyte antigen; DSA, donor-specific antibody; MFI, mean fluorescence intensity; ABMR, antibody-mediated rejection; TCMR, T-cell-mediated rejection; g, glomerulitis; ptc, peritubular capillaritis.

a) Anti-HLA-DR15 (1,461) preformed DSA was detected before transplantation.

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Table 4.
Clinical review data and biopsy results of three patients with anti-HLA-DR 51/52/53 highest DSA without anti-HLA-DRB1 DSA
HLA typing (recipient/donor) Age (yr)/sex Type of transplant Year after transplantation DR51/52/53 (recipient/donor) DSA (MFI) Cr Kidney biopsy
A2, A24, B52, -, Cw1, -, DR15, -/A2, -, B44, -, Cw1, -, DR15, DR7 58/Male Living-related donor KT 20.5 DR51, -/DR51, DR53 DR53 (18,752) without other HLA antibodies 3.99 ABMR, grade II C4d(+, diffuse, g1, ptc2
A2, A11, B62, -, DR4, DR14/A2, A30, B64, B62, DR4, DR15 52/Male Living-related donor KT 9.1 DR52, DR53/DR51, DR53 DR51 (17,848) without other HLA antibodies 1.70 TCR and ABMR C4d(+, diffuse, g1, ptc3
A2, A11, B46, B71, Cw1, Cw8, DR8, DR9/A24, A11, B35, B71, Cw3, Cw8, DR9, DR15 62/Male Living-related donor KT 8.7 DR53, -/DR51, DR53 DR51 (12,172), A24 (1,498) 2.25 ABMR, grade II C4d(+, diffuse, g1, ptc3

HLA, human leukocyte antigen; DSA, donor-specific antibody; MFI, mean fluorescence intensity; Cr, creatinine; KT, kidney transplantation; ABMR, antibody-mediated rejection; TCR, T-cell-mediated rejection; g, glomerulitis; ptc, peritubular capillaritis.

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Table 5.
Clinical data and biopsy results of 10 patients who developed both anti-DQ DSA and anti-HLA-DR or class I DSA
DSA to HLA-DQ (MFI) DSA to HLA-DR or class I (MFI) Cr Day after transplantation Kidney biopsy
DQ6 (7,583) DR14 (4,843) NA 3,670 ABMR, grade II, C4d(+, diffuse), g2, ptc1
DQ9 (9,432) DR9 (8,633) 2.07 4,120 ABMR, grade II, C4d(+, diffuse), g0, ptc2
DQ2 (20,687) DR7 (2,109) 2.56 4,681 Chronic ABMR, C4d(+, diffuse), g3, ptc1
DQ7 (12,702) DR12 (453) 1.47 869 ABMR, grade II, C4d(+, diffuse), g1, ptc1
DQ8 (12,386) DR4 (1,764) 3.18 3,095 Chronic ABMR, C4d(+, focal), g3, ptc1
DQ9 (17,644) DR9 (15,822) 2.10 2,996 ABMR, grade II, C4d(+, diffuse), g1, ptc3
DQ7 (15,059) DR11 (1,397) 2.34 1,785 Chronic ABMR, C4d(+, diffuse), g3, ptc2
DQ9 (15,609) DR9 (658) 1.59 441 C4d(+/–, weak), g0, ptc3
DQ6 (9,456) A2 (1,100) 2.02 265 ABMR, grade II, C4d(+, diffuse), g0, ptc2
DQ8 (8,035) B44 (416) NA 2,611 ABMR, grade II, C4d(+, diffuse), g2, ptc2

DSA, donor-specific antibody; HLA, human leukocyte antigen; MFI, mean fluorescence intensity; Cr, creatinine; NA, not applicable; ABMR, antibody-mediated rejection; g, glomerulitis; ptc, peritubular capillaritis.

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