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Updated: Aug 9, 2026
Ion Exchange Chromatography (IEX) Coupled to Multi-angle Light Scattering (MALS) for Protein Separation and Characterization
Published on: April 5, 2019
Insights
The 1994 International Cell Exchange demonstrated improved accuracy in human leukocyte antigen (HLA) typing for both Class I and Class II antigens. Continuous participation and retyping efforts led to enhanced detection rates and reduced discrepancies in HLA serology and DNA typing.
Area of Science:
- Immunogenetics and Histocompatibility
- Molecular Biology and Genetics
- Clinical Laboratory Science
Background:
- The International Cell Exchange program facilitates standardized human leukocyte antigen (HLA) typing.
- Accurate HLA typing is critical for organ transplantation and disease association studies.
- Previous assessments highlighted variability in typing accuracy across laboratories.
Purpose of the Study:
- To summarize the results of the 1994 International Cell Exchange for Class I and Class II HLA antigens.
- To compare serologic and DNA-based typing methods for Class II antigens.
- To evaluate typing accuracy, detection levels, and discrepancy rates for specific HLA loci.
Main Methods:
- Analysis of typing data from 281 laboratories for Class I antigens and 119/74 laboratories for Class II serologic/DNA typing.
- Determination of average and high detection levels for 16 A-locus and 27 B-locus antigens.
- Comparison of discrepancy rates for frequently typed A-locus and B-locus antigens, including false-negative and false-positive rates.
Main Results:
- High detection rates (≥95%) were achieved for most A-locus (12/16) and B-locus (10/27) antigens.
- Lower agreement (<80%) was observed for specific antigens, including A74 and several B-locus antigens (e.g., B46, B75).
- False-negative rates were higher for B-locus than A-locus antigens, with B62 showing the highest false-positive rate; B70 discrepancy rates decreased over time.
- Significant improvements in antigen detection were noted upon retyping reference cells and long-term donor typing.
- Updated sequences for Class I exchange cells and identified variants in both Class I and Class II specificities were reported.
Conclusions:
- The 1994 International Cell Exchange demonstrated overall high accuracy in HLA typing, with notable improvements over time.
- Continuous participation and re-evaluation of typing methods enhance antigen detection and reduce errors.
- The program provides valuable data for refining HLA typing protocols and understanding genetic diversity.
Abstract:
1. We summarize typings of 40 cells for Class I antigens and 20 cultured cell lines for Class II antigens through the International Cell Exchange in 1994. Serologic Class II typings were compared with DNA typings for the same 20 cells. Two hundred eighty-one laboratories participated in the monthly Class I Serum Exchange. One hundred nineteen serology laboratories and 74 DNA laboratories reported Class II specificities on a monthly basis. 2. The average detection levels, as well as the high detection levels, were determined for 16 A-locus and 27 B-locus antigens. Mean detection rates of 95% or greater average detection were obtained for 12 A-locus and 10 B-locus antigens. Lower than 80% agreement was calculated for one A-locus antigen (A74) and 7 B-locus (B46, B48, B61, B67, B73, B75, B77) antigens. 3. We compared discrepancy rates of 10 A-locus and 7 B-locus antigens typed 3 times or more. The false-negative discrepancy rates, i.e. how often the antigen was missed, were greater for more of the B-locus specificities than for the A-locus antigens. B62, having the highest false-positive rate, tended to be overassigned. The discrepancy rates, especially the false-negative rate, for B70 were shown to decrease over a 7-year period. 4. In 1994, 8 laboratories attained records of total no misses for all analyzed antigens. Twelve laboratories had final records of only one discrepancy, and 5 laboratories had impressive perfect records (zero false negatives and false positives) for their yearly antigen reports. 5. Retyping of 12 Class I and 8 Class II reference cells showed improved detection of antigens. Results of a donor typed 4 times over 11 years demonstrated marked improvement, nearly doubling for A33, B38, and B75. Two cells first typed in 1991, then retyped in 1994, showed improved detection for Class II splits by serology and DNA typing. 6. We updated the list of sequenced Class I Exchange cells. Seven new cells were added as well as confirmatory sequence data for A*2403 to the A9.3 (cell 762) and a new B*0705 (cell 715) for previously listed cells. Variants detected in the exchanges for Class I (DT/B7x40, B15, B16, B5x53) and Class II (DRB1*1111, DQB1*02, DR1, DR2) specificities were discussed. Eleven rare or unusual Class II haplotypes were studied in 1994. 7. The mean detection levels were determined for 9 broad DR and 4 DQ specificities by serology and compared to those attained for the respective generic (low resolution) DNA typing.(ABSTRACT TRUNCATED AT 400 WORDS)
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