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Kim, Choi, and Oh: Human Leukocyte Antigen Typing Proficiency Surveys in Korea, 2005-2006
Original Article

Korean J Leg Med 2007;27(6):442-450.

Published online: 14 February 2007

DOI: https://doi.org/10.3343/kjlm.2007.27.6.442

Human Leukocyte Antigen Typing Proficiency Surveys in Korea, 2005-2006

Myeong-Hee Kim, M.D., Sung-Eun Choi, M.A., Heung-Bum Oh, M.D.

Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Korea

Received 13 September 200729 October 2007       Accepted 3 November 2007

Copyright © 2007 by the Korean Society for Legal Medicine

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

To monitor the performance of histocompatibility testing laboratories, HLA proficiency survey in Korea has been conducted biannually since 1996. In this report, we summarized the results of the surveys performed in recent two years (2005-2006).

Methods

A total of four proficiency surveys were performed, in which 59-61 laboratories participated. Each survey included three tests for HLA class I (serology and DNA) and class II (DNA) typing and six tests for HLA crossmatch.

Results

The overall concordance of serologic typing was 98.9% (355/359) for HLA-A, 97.5% (350/359) for HLA-B, and 94.7% (337/356) for HLA-C. The antigens assigned correctly by less than 95% of the participating laboratories were A26 (93.8%), B38 (94.2%), Cw3/Cw10 (90.9%), Cw6 (94.4%), and Cw8 (74.3%). The overall concordance rates of DNA typing were 99.6% (533/535) for HLA-A, 99.8% (539/540) for HLA-B, and 100% (392/392) for HLA-C. Correct assignment of HLA-DRB1 and -DQB1 was reported by 99.2% (98.1-100%) and 96.7% (88.9-100%) for the generic level and 100% and 95.8% (75-100%) for the allelic level, respectively. On the average 3.8% (0-7.7%) of the total laboratories showed unacceptable results in the crossmatch tests.

Conclusions

The rates of correct antigen identification and of unacceptable crossmatch were similar to those of previous surveys, which were considered satisfactory. The Korean proficiency survey program may have contributed to a high quality of HLA tests today and should be continued for further improvements of the tests tomorrow.

Keywords: Proficiency survey, HLA typing, HLA crossmatch

REFERENCES

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Table 1.
HLA proficiency surveys performed during 2005-2006 and response rates of the surveys
Trial No. Trial date No. of laboratories (participants/reply) No. of laboratories (reply)
HLA class I serology HLA class I DNA HLA class II DNA Crossmatch
15 2005. 4. 18 59/59 35-36 39-40 56 46-47
16 2005. 11. 7 59/59 33 43 55 46
17 2006. 4. 17 61/60 29 45 55 45
18 2006. 10. 23 60/60 22 51-52 56 47
Table 2.
HLA DNA typing kits used by the laboratories participating in the HLA proficiency survey∗
HLA tests No. of laboratories Methods Kits (No. of laboratories)
HLA-A, B, C 52 SSOP reverse Murex INNO LiPA HLA-A,B,C (19)
      Dynal RELI HLA A,B,C (13)
    SSP Biotest HLA-A,B,C SSPtray Kit (3)
      Biotest HLA-AB/DR SSPtray Kit (2)
      Biotest HLA-A SSPtray Kit (1)
      Biosewoom HLA-AB/DR PCR/SSP Kit (2)
      One lambda Micro Generic HLA Class I DNA Typing (ABC) (1)
      One lambda Micro Generic HLA Class I & Class II DNA Typing (AB/DR) (1)
    SBT Biosewoom HLA-A,B,C PCR/SBT Kit (2)
      In house (1)
      Other (7)
HLA-DR 56 SSOP reverse Murex INNO LiPA HLA-DRB1 (21)
      Dynal RELI HLA-DRB1 (14)
      Biotest ELPHA HLA-DRB1 LowRes (1)
    SSP Biotest HLA-DRB SSP Kit (3)
      Biotest HLA-AB/DR SSPtray Kit (1)
      Biosewoom HLA-AB/DR PCR/SSP Kit (3)
      One lambda Micro Generic HLA Class II DNA Typing (DR) (2)
      One lambda Micro Generic HLA Class I & Class II DNA Typing (AB/DR) (1)
    SBT Biosewoom HLA-DRB1 PCR/SBT Kit (2)
      In house (1)
      Other (7)
HLA-DQ 9 SSOP reverse Murex INNO LiPA HLA-DQB (1)
      Dynal RELI HLA-DQB (1)
    SSP Biotest HLA-DQB SSP Kit (1)
      One lambda Micro Generic HLA Class II DNA Typing (DQ) (1)
    SBT Biosewoom HLA-DQB1 PCR/SBT Kit (1)
      In house (1)
      Other (2)
    RFLP In house (1)

∗ Test methods reported in Trial No. 18 (2006. 10. 23).

Abbreviations: SSOP, sequence specific oligonucleotide probe; SSP, sequence specific primer; SBT, sequence-based typing; RFLP, restriction fragment length polymorphism.

Table 3.
Laboratory consensus in serological identification of HLA-A, -B, and -C in four trials of proficiency survey
Trial No. Cell No. HLA-A (%) HLA-B (%) HLA-C (%)
Consensus False positive Consensus False positive Consensus False positive
15 C05-1 A2 (97.2) A1 (2.8) B13 (100)   Cw1 (100)  
    A30 (100)   B27 (100)   Cw6 (94.4) Cw2 (2.8), Blank (2.8)
  C05-2 A26 (100)   B13 (100)   Cw1 (100)  
    Blank (100)   B61 (97.2) Blank (2.8) Cw3 (100)  
  C05-3 A2 (100)   B14/B64 (100)   Cw7 (100)  
    A30 (100)   B38 (94.2) B63 (2.9), Blank (2.9) Cw8 (74.3) Blank (25.7)
16 C05-4 A2 (100)   B35 (100)   Cw3/Cw10 (100)  
    A26 (100)   B54 (100)   Blank (100)  
  C05-5 A2 (100)   B27 (100)   Cw1 (100)  
    A26 (100)   B54 (100)   Cw3/Cw10 (90.9) Blank (9.1)
  C05-6 A11 (100)   B8 (100)   Cw7 (100)  
    A26 (93.8) A10 (6.2) B39 (100)   Blank (100)  
17 C06-1 A24 (100)   B51 (100)   Cw1 (100)  
    Blank (100)   B59(100)   Blank (100)  
  C06-2 A2 (100)   B39 (100)   Cw4 (100)  
    A24 (100)   B62 (100)   Cw7 (100)  
  C06-3 A2 (100)   B60 (100)   Cw3 (100)  
    Blank (100)   B70/B71 (100)   Cw7 (100)  
18 C06-4 A2 (100)   B51 (100)   Cw4 (100)  
    A11 (100)   B62 (100)   Blank (100)  
  C06-5 A11 (100)   B35 (100)   Cw3 (100)  
    A24 (100)   B60 (100)   Blank (100)  
  C06-6 A2 (100)   B13 (100)   Cw4 (100)  
    A11 (100)   B60 (100)   Blank (95.2) Cw6 (4.8)
Total % (N)   98.9% (355/359) 97.5% (350/359)   94.7% (337/356)  
Table 4.
HLA-A, -B, -C antigens showing a low consensus (<95%) in serological identification and comparison of typing kits used
HLA antigen Cell No. Consensus % (No. of labs)
A kit B kit C kit Total
A26 C05-6 92.0 (23/25) 100 (7/7)   93.9 (30/32)
B38 C05-3 92.6 (25/27) 100 (8/8)   94.2 (33/35)
Cw3/Cw10 C05-5 96.0 (24/25) 85.7 (6/7) 0.0 (0/1) 90.9 (30/33)
Cw6 C05-1 92.6 (25/27) 100 (9/9)   94.4 (34/36)
Cw8 C05-3 96.3 (26/27) 0.0 (0/8)   74.3 (26/35)
Table 5.
Laboratory consensus in DNA typing of HLA-A, -B, and C in 4 trials of proficiency survey
Trial No. Cell No. HLA-A (%, N) HLA-B (%, N) HLA-C (%, N)
Consensus Consensus Consensus
15 C05-1 A2 (100, 39/39), A30 (97.4, 38/39)∗ B13 (100, 39/39), B27 (100, 39/39) Cw1 (100, 29/29), Cw6 (100, 29/29)
  C05-2 A26 (100, 40/40), Blank (100, 40/40) B13 (100, 39/39), B40/B61 (100, 39/39) Cw1 (100, 29/29), Cw3/Cw10 (100, 29/29)
  C05-3 A2 (100, 39/39), A30 (100, 39/39) B14/B64 (100, 41/41), B38 (100, 41/41) Cw7 (100, 29/29), Cw8 (100, 29/29)
16 C05-4 A2 (97.7, 42/43)†, A26 (100, 43/43) B35 (100, 43/43), B54 (100, 43/43) Cw3 (100, 31/31), Cw14 (100, 31/31)
  C05-5 A2 (100, 42/42), A26 (100, 42/42) B27 (100, 43/43), B54 (100, 43/43) Cw1 (100, 31/31), Cw3 (100, 31/31)
  C05-6 A11 (100, 42/42), A26 (100, 42/42) B8 (100, 43/43), B39 (100, 42/42) Cw7 (100, 31/31), Cw7/Blank (100, 27/27)
17 C06-1 A24 (100, 45/45), Blank/A24 (100, 45/45) B51 (100, 45/45), B59 (100, 45/45) Cw1 (100, 32/32), Cw14/Blank (100, 32/32)
  C06-2 A2 (100, 45/45), A24 (100, 45/45) B39 (100, 46/46), B15 (100, 46/46) Cw4 (100, 32/32), Cw7 (100, 32/32)
  C06-3 A2 (100, 45/45), Blank/A2 (100, 45/45) B40 (100, 46/46), B15 (100, 46/46) Cw3 (100, 32/32), Cw7 (100, 32/32)
18 C06-4 A2 (100, 52/52), A11 (100, 52/52) B51 (100, 52/52), B15 (98.1, 51/52)‡ Cw4 (100, 39/39), Cw14/Blank (100, 39/39)
  C06-5 A11 (100, 51/51), A24 (100, 51/51) B35 (100, 51/51), B40 (100, 51/51) Cw3 (100, 38/38), Cw3/Blank (100, 38/38)
  C06-6 A2 (100, 52/52), A11 (100, 52/52) B13 (100, 52/52), B40 (100, 52/52) Cw4 (100, 39/39), Cw14/Blank (100, 39/39)
Total% (No. of tests)   99.6% (533/535) 99.8% (539/540) 100% (392/392)

∗ A3 was reported in 1 lab.;

† A blank was reported in 1 lab.;

‡ B78 was reported in 1 lab.

Table 6.
Laboratory consensus in identification of HLA-DRB1 alleles in 4 trials of proficiency survey
Trial No. Cell No. HLA-DRB1 consensus (%, N)
Generic or serologic equivalent typing Allele typing  
15 C05-1 DR1 (100, 56/56), DR7 (100, 56/56) ∗0101 (100, 6/6) ∗0701 (100, 6/6)
  C05-2 DR12 (100, 56/56), DR15 (100, 56/56) ∗1202 (100, 6/6) ∗1501 (100, 6/6)
  C05-3 DR4 (100, 56/56), DR15 (100, 56/56) ∗0404 (100, 6/6) ∗1502 (100, 6/6)
16 C05-4 DR9 (98.1, 51/52)∗, DR14 (98.1, 51/52)† ∗0901 (100, 7/7) ∗1401 (100, 7/7)
  C05-5 DR1 (100, 52/52), DR4 (98.1, 51/52)‡ ∗0101 (100, 7/7) ∗0405 (100, 7/7)
  C05-6 DR3 (100, 52/52), DR4 (100, 52/52) ∗0301 (100, 8/8) ∗0405 (100, 7/7)
17 C06-1 DR4 (100, 55/55), Blank/DR4 (100, 55/55) ∗0404 (100, 9/9) ∗0405 (100, 9/9)
  C06-2 DR4 (100, 55/55), DR8 (100, 55/55) ∗0406 (100, 9/9) ∗0803 (100, 9/9)
  C06-3 DR3 (100, 55/55), DR9 (100, 55/55) ∗0301 (100, 9/9) ∗0901 (100, 9/9)
18 C06-4 DR4 (98.2, 55/56)§, DR11 (100, 56/56) ∗0406 (100, 12/12) ∗1101 (100, 11/11)
  C06-5 DR9 (98.2, 55/56)‖, DR15 (100, 56/56) ∗0901 (100, 11/11) ∗1501 (100, 11/11)
  C06-6 DR7 (100, 56/56), DR12 (100, 56/56) ∗0701 (100, 11/11) ∗1202 (100, 11/11)
Total% (No. of tests) 99.2% (652/657) 100% (101/101)  

∗ DR14 was reported in 1 lab.;

† DR6 was reported in 1 lab.;

‡ DR1 was reported in 1 lab.;

§ DR99 was reported in 1 lab.;

‖ DR7 was reported in 1 lab.

Table 7.
Laboratory consensus in identification of HLA-DQB1 antigens in 4 trials of proficiency survey
Trial No. Cell No. HLA-DQB1 consensus (%, N)
Generic or serologic equivalent typing Allele typing  
15 C05-1 DQ2 (100, 12/12), DQ5 (100, 12/12) ∗0202 (75.0, 3/4)∗ ∗0501 (100, 4/4)
  C05-2 DQ3/DQ7 (100, 12/12), DQ6 (100, 12/12) ∗0301 (100, 4/4) ∗0602 (100, 4/4)
  C05-3 DQ4 (91.7, 11/12)†, DQ5 (100, 12/12) ∗0402 (100, 4/4) ∗0501 (100, 4/4)
16 C05-4 DQ3 (100, 11/11), DQ5 (100, 11/11) ∗0303 (100, 4/4) ∗0502 (100, 4/4)
  C05-5 DQ4 (100, 11/11), DQ5 (100, 11/11) ∗0401 (100, 4/4) ∗0501 (100, 4/4)
  C05-6 DQ2 (100, 11/11), DQ3 (100, 11/11) ∗0201 (100, 3/3) ∗0303 (100, 4/4)
17 C06-1 DQ4 (100, 9/9), DQ3 (100, 9/9) ∗0401 (100, 4/4) ∗0302 (100, 4/4)
  C06-2 DQ6 (88.9, 8/9)‡, DQ3 (100, 9/9) ∗0601 (100, 4/4) ∗0302 (100, 4/4)
  C06-3 DQ2 (100, 9/9), DQ3 (88.9, 8/9)§ ∗0201 (100, 4/4) ∗0303 (100, 4/4)
18 C06-4 DQ3 (100, 9/9), DQ3 (100, 9/9) ∗0301 (75.0, 3/4)‖ ∗0302 (100, 4/4)
  C06-5 DQ6 (100, 9/9), DQ3 (100, 8/9) ∗0602 (100, 4/4) ∗0303 (100, 4/4)
  C06-6 DQ2 (100, 9/9), DQ3 (100, 9/9) ∗0202 (100, 4/4) ∗0301 (100, 4/4)
Total% (No. of tests)   96.7% (119/123) 95.8% (46/48)  

∗ DQ ∗0201 was reported in 1 lab.;

† DQ Blank was reported in 1 lab.;

‡ DQ99 was reported in 1 lab.;

§ DQ99 was reported in 1 lab.;

‖ DQ ∗0303 was reported in 1 lab.;

DQ99 was reported in 1 lab.

Table 8.
Laboratory consensus in HLA crossmatch results by cytotoxicity tests in 4 trials of proficiency survey
Trial No. Cell × serum Identification of incompatible crossmatch % (N) Unacceptable % (N of tests)
T-NIH or T-Warm T-Long T-AHG
Positive Negative Positive Negative Positive Negative
15 C05-1 × S05-1 29.5 (13/44) 70.5 (31/44) 35.3 (6/17) 64.7 (11/17) 77.1 (27/35) 22.9 (8/35) NA
  C05-1 × S05-2 18.2 (8/44) 81.8 (36/44) 29.4 (5/17) 70.6 (12/17) 60 (21/35) 40 (14/35) NA
  C05-2 × S05-1 4.5 (2/44) 95.5 (42/44) 5.9 (1/17) 94.1 (16/17) 5.7 (2/35) 94.3 (33/35) 5.2 (5/96)
  C05-2 × S05-2 84.1 (37/44) 15.9 (7/44) 88.2 (15/17) 11.8 (2/17) 94.3 (33/35) 5.7 (2/35) 5.7 (2/35)
  C05-3 × S05-1 44.2 (19/43) 55.8 (24/43) 62.5 (10/16) 37.5 (6/16) 85.7 (30/35) 14.3 (5/35) NA
  C05-3 × S05-2 0 (0/43) 100 (43/43) 0 (0/16) 100 (16/16) 0 (0/35) 100 (35/35) 0 (0/94)
16 C05-4 × S05-3 82.1 (32/39) 17.9 (7/39) 85.7 (12/14) 14.3 (2/14) 97.2 (35/36) 2.8 (1/36) 2.8 (1/36)
  C05-4 × S05-4 85 (34/40) 15 (6/40) 100 (14/14) 0 (0/14) 100 (36/36) 0 (0/36) 0 (0/50)
  C05-5 × S05-3 61 (25/41) 39 (16/41) 80 (12/15) 20 (3/15) 97.2 (35/36) 2.8 (1/36) 2.8 (1/36)
  C05-5 × S05-4 58.5 (24/41) 41.5 (17/41) 80 (12/15) 20 (3/15) 97.2 (35/36) 2.8 (1/36) 2.8 (1/36)
  C05-6 × S05-3 11.9 (5/42) 88.1 (37/42) 13.3 (2/15) 86.7 (13/15) 25 (9/36) 75 (27/36) NA
  C05-6 × S05-4 50 (21/42) 50 (21/42) 66.7 (10/15) 33.3 (5/15) 97.2 (35/36) 2.8 (1/36) 2.8 (1/36)
17 C06-1 × S06-1 82.5 (33/40) 17.5 (7/40) 93.3 (14/15) 6.7 (1/15) 91.9 (34/37) 8.1 (3/37) 7.7 (4/52)
  C06-1 × S06-2 80 (32/40) 20 (8/40) 20 (3/15) 80 (12/15) 29.7 (11/37) 70.3 (26/37) NA
  C06-2 × S06-1 82.5 (33/40) 17.5 (7/40) 80 (12/15) 20 (3/15) 94.6 (35/37) 5.4 (2/37) 5.4 (2/37)
  C06-2 × S06-2 87.5 (35/40) 12.5 (5/40) 86.7 (13/15) 13.3 (2/15) 100 (37/37) 0 (0/37) 0 (0/37)
  C06-3 × S06-1 0 (0/40) 100 (40/40) 0 (0/15) 100 (15/15) 5.4 (2/37) 94.6 (35/37) 2.2 (2/92)
  C06-3 × S06-2 92.5 (37/40) 7.5 (3/40) 93.3 (14/15) 6.7 (1/15) 100 (37/37) 0 (0/37) 4.3 (4/92)
18 C06-4 × S06-3 50 (22/44) 50 (22/44) 46.7 (7/15) 53.3 (8/15) 80 (32/40) 20 (8/40) NA
  C06-4 × S06-4 40.9 (18/44) 59.1 (26/44) 33.3 (5/15) 66.7 (10/15) 62.5 (25/40) 37.5 (15/40) NA
  C06-5 × S06-3 97.7 (43/44) 2.3 (1/44) 93.3 (14/15) 6.7 (1/15) 100 (40/40) 0 (0/40) 2 (2/99)
  C06-5 × S06-4 34.1 (15/44) 65.9 (29/44) 26.7 (4/15) 73.3 (11/15) 52.5 (21/40) 47.5 (19/40) NA
  C06-6 × S06-3 88.6 (39/44) 11.4 (5/44) 93.3 (14/15) 6.7 (1/15) 100 (40/40) 0 (0/40) 1.8 (1/55)
  C06-6 × S06-4 40.9 (18/44) 59.1 (26/44) 40 (6/15) 60 (9/15) 72.5 (29/40) 27.5 (11/40) NA

Abbreviation: NA, not applicable.

Table 9.
Laboratory consensus in identification of various HLA-A, -B and -C antigens on 12 whole blood specimens
HLA antigen No. of tests Consensus % HLA antigen No. of tests Consensus %
Mean Range Mean Range
A2 8 99.7 97.2-100 B8 1 100 100
A11 4 100 100 B13 3 100 100
A24 3 100 100 B14/B64 1 100 100
A26 4 98.5 93.8-100 B27 2 100 100
A30 2 100 100 B35 2 100 100
        B38 1 94.2 94.2
        B39 2 100 100
        B51 2 100 100
Cw1 4 100 100 B54 2 100 100
Cw3 5 98.2 90.9-100 B59 1 100 100
Cw4 3 100 100 B60 3 100 100
Cw6 1 94.4 94.4 B61 1 97.2 97.2
Cw7 4 100 100 B62 2 100 100
Cw8 1 74.3 74.3 B70/B71 1 100 100
        Bw4 7 97.7 93.5-100
        Bw6 10 98.6 93.5-100
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