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The 1993 cell typings of the International Cell Exchange
Insights
The International Cell Exchange improves HLA typing accuracy through serological and DNA methods. Continuous monitoring and retyping enhance detection of Class I and Class II antigens, reducing errors.
Area of Science:
- Immunogenetics
- Histocompatibility Antigen Typing
- Molecular Biology
Background:
- The International Cell Exchange facilitates global collaboration in histocompatibility antigen typing.
- Accurate human leukocyte antigen (HLA) typing is crucial for organ transplantation and disease association studies.
- Both serological and DNA-based typing methods are employed, each with unique strengths and limitations.
Purpose of the Study:
- To summarize typing results for Class I and Class II antigens from the International Cell Exchange.
- To compare serological and DNA typing methods for Class II specificities.
- To assess the accuracy and identify areas for improvement in HLA typing proficiency.
Main Methods:
- Analysis of serological and DNA typing data from participating laboratories.
- Monthly exchange of Class I and Class II cell lines for typing.
- Comparison of discrepancy rates (false negatives and false positives) for various HLA loci.
- Sequencing of selected cell lines to confirm new or rare HLA variants.
Main Results:
- High average detection levels (≥95%) were achieved for most A-locus and B-locus antigens, with noted improvements in detecting specificities like B76 and B7801.
- Discrepancy rates for B-locus antigens, particularly false negatives, remained higher than for A-locus antigens.
- DNA typing demonstrated high agreement levels for broad Class II antigens (≥90%), while serological typing of specific Class II splits showed variable accuracy, with some as low as 15%.
Conclusions:
- The International Cell Exchange plays a vital role in enhancing HLA typing accuracy and identifying typing challenges.
- Continuous monitoring and retyping efforts have led to improved antigen detection and reduced discrepancies.
- While DNA typing shows high proficiency for broad Class II antigens, serological typing of specific splits requires further refinement.
Abstract:
1. This is a summary of the typings for 40 cells for Class I antigens and 20 cultured cell lines for Class II antigens through the International Cell Exchange. Serological typings were compared with DNA typing reports for Class II specificities. Presently, 283 laboratories participate in the monthly Class I exchange. Class II results were received from 124 serology labs and 81 DNA labs on a monthly basis. 2. In 1993, 12 A-locus antigens were typed and 8 specificities reached levels of 95% or greater average detection. Thirteen of the 33 B-locus antigens showed 95% or better mean agreement levels. There was an improvement in detection of B76 and B7801. 3. Discrepancy rates of 7 A-locus and 9 B-locus antigens typed 3 or more times were compared with the overall rates for each respective locus. The discrepancy rate of false negatives, ie, how often the antigen was missed for the recognized B-locus specificities, continued to be greater than those for the A-locus antigens. The discrepancy rates, especially the percent false-positive, decreased for A33 during the recent 6-year period. 4. We showed the number of labs with their total of false-negatives and false-positives. Twelve labs attained a final total of no misses for all antigens. In 1993, 11 labs achieved impressive perfect records (zero false negative and false positive) for all analyzed antigens. 5. Retyping results of 2 donors showed improved antigen detection, particularly of A2403, B70, and B76. 6. Eleven cells typed in previous cell exchanges as having new or rare variants were sequenced recently. The B*5102 and B*5901 cells were retyped as reference cells. A new A-locus variant detected in previous exchanges was recently confirmed by sequence work as A*8001. New variants of B5 and B22 were discussed. 7. In addition to the mean detection rates, the low and high levels were determined for 15 broad (11 DR & 4 DQ) specificities by serology and compared with those attained for the respective generic (low-resolution) DNA typing. Only 2 broad antigens (DR10 and DQ4) had less than a 90% agreement level by serology. All of the generic types reached over 95% average detection levels, with the exception of DQB1*04, which reached 90% mean detection. 8. Detection of 8 Class II splits (4 DR & 4 DQ) continued to pose problems in serology, ranging from as low as 15% for DQ5 and DQ9 to an average detection level of 61% for DR15.(ABSTRACT TRUNCATED AT 400 WORDS)
