The UCLA International Cell Exchange has followed the progress in HLA typing since it began with 85 participating laboratories in 1974 and has expanded to 200 participants worldwide . The original goal of the Cell Exchange was to standardize the practice of HLA typing. This was an important undertaking because tissue typing for organ transplantation, disease studies, and population studies was dependent upon human typing sera obtained in very limited quantities, primarily from multiparous women. The accuracy of these reagents was dependent upon local methods of assessing the specificities of the anti-HLA antibodies and the volumes made it difficult to distribute sufficient quantities for use by everyone who performed HLA testing.
The Cell Exchange provided an alternative strategy, distributing the same cells to many laboratories for HLA typing. Each laboratory would report their results to UCLA and then receive a report of every other laboratory's results for comparison. This provided the laboratories a means for evaluating their typing results and for identifying the weaknesses in their panels of typing sera. As the complexity of the HLA system defined by antibody reagents grew, the Cell Exchange focused its efforts on providing challenging cell types - those that included "rare" HLA antigens or unusual combinations of antigens that might be difficult to discriminate.
A serum exchange was added in 1981, to check for anti-HLA antibody specificities. Accuracy of specificity and degree of sensitivity by various methods are assessed. Sera with complexes, interlocus antibodies, and reagent-quality antibodies are examined. This exchange helps labs detect problems in their serum screening panels and procedures. In 1987, testing for Class II typing was initiated with the first shipment of 2 lymphoblastoid cell lines. In 1990, DNA-based typing results were first reported in correlation with the serologic results. Cells with rare alleles and unusual DR-DQ associations are studied. DRB1, DRB3, DRB4, DRB5, DQB1, DQA1, and DPB1 alleles are evaluated. These cell lines can be maintained in culture and used as reference lines.
In 1994, the Cell Exchange initiated offering the same cells for molecular typing as for serologic typing for Class I. The data from the parallel typings is instrumental in identifying serologic equivalents for Class I and Class II alleles that previously had little or no serologic information. This information is routinely added to the HLA Dictionary. In 1997, DNA extracts from cells with unusual class I alleles were provided to participating laboratories. Many of these extracts were from the reference cells sequenced for rare alleles, thus giving laboratories the opportunity to type them, whereas they may not detect them in routine typing them in their local populations. Having these cells typed by numerous laboratories will help to achieve standardization in the typing of rare types.
In 2005, the International KIR Exchange was integrated within the framework of the International Cell Exchange, by offering reference DNA samples for KIR gene typing. The goals of this program are to standardize typing of KIR genes and alleles, and to identify new alleles.
In February 2007, a pilot study for MICA (class I chain-related molecule A) typing was initiated by sending samples to a select number of laboratories. This will provide an opportunity to compare typing results from different technologies. In the near future, this will expand to encompass MICA antibody identification. The goals are to standardize typing of MICA alleles and MICA antibody identification, as well as to identify new alleles.
In all the exchanges, the goals are to provide samples to validate methods and reagents, and to provide external quality control. By offering a forum for data exchange and discussion, the Cell Exchange has played a key role in international standardization. The UCLA International Cell Exchange has recorded the progress of HLA typing in a number of publications and presentations at national and international meetings.
The Cell Exchange has helped laboratories to sharpen their skills and has monitored and published the development of tissue typing over the years. The goal of providing unusual types or combinations to participants was often accomplished by identifying cells that gave ambiguous or incomplete results. Many of these cells were provided to the Cell Exchange by the participating laboratories and often these challenging HLA types were found to include "variants," which represented new alleles that were not defined by serology.
The problem of how to ship viable lymphocytes to locations throughout the world was solved by Dr Min Sik Park in 1973 (Park MS and Terasaki PI, Transplantation (1974) 18, 520-524) and permitted the evolution of international testing. This simple method is still used today by organizations involved in proficiency testing as well as for routine exchanges of material among laboratories.
Over the years, the Cell Exchange has helped to identify numerous new or rare antigens. In the course of standardizing specificities to attain international agreement, the exchanges have identified duplicate names for the same specificity and the same name being used for different ones, for example, A26 versus A66 for the antigen encoded by A*6601, and A34 versus A66 for the one encoded by A*6602.
More than 30 cells typed in the Cell Exchange now serve as reference cells for Class I alleles, confirmed through subsequent study. Examples of variants which were extensively studied in previous cell exchanges and received formal designations by the WHO Nomenclature Committee are: A9.3 (A*2403), BN21 (B*4005), B5.35 (B*5102), 5Y/8w58/BSNA (B*7801, B*7802), numerous B15 variants (B*1508, B*1511, B*1512, B*1515), and DT (B*8101). The Cell Exchange data has provided vital correlation between alleles and serologic names in many cases, such as establishing B*1518 as B71 and Cw*1701 as a short Cw7. Among the numerous alleles detected in exchange cells were A*1104, A*6803, B*1304, and B*4012. Our Cell Exchange continues to study serological variants not yet recognized and bring them to the forefront for validation by sequence analysis.
By routinely contributing data to be used in the HLA Dictionary that offers allele-serologic equivalents, the Cell Exchange provides valuable information to be used in matching searches for unrelated donors in databases with mixtures of data attained using different techniques. This is important during the transition period as labs migrate to the exclusive use of molecular testing methods.
The International Cell Exchange has a long and consistent history of service to the histocompatibility community. The Cell Exchange has operated continuously for more than thirty years, sending cells and sera, accounting for more than 3000 reference samples. The close of 2006 will mark the completion of 322 cell exchanges, encompassing 1288 cells for Class I serology, 920 sera for anti-HLA antibody identification, 386 cells for Class II serology, 310 cells for Class II DNA typing, and 464 cells for Class I DNA typing. The exchange has also provided 376 DNA extracts for HLA Class I testing.
|AROUND THE WORLD|
|Argentina||CABA||Hong Kong||New Zealand||Auckland|
|Brisbane QLD||Ireland||Dublin||Saudi Arabia||Riyadh|
|West Melbourne, VIC||Jerusalem||South Africa||Arcadia|
|China||BDA Beijing||Korea, Republic Of||Seongnam-si, Gyeonggi-do||Switzerland||Geneva 14|
|Shanghai||Suwon-si||United Kingdom||Bromborough, Wirral|
|Finland||Helsinki||Lembah Pantai, Kuala Lumpur||London|
|France||Paris Cedex 10||Mexico||Aguascalientes||Leeds England|
|Toulouse Cedex 9||Maastricht||Uruguay||Montevideo|
|Los Angeles||Worcester||New York|
|Hawaii||Honolulu||North Carolina||Burlington||Washington DC|
|New Jersey||New Providence||Waukesha|
Collaborative efforts through international and regional workshops have played major roles in advancing HLA typing. Since 1974, the International Cell Exchange has played an important role in improving HLA typing in the interim between workshops. The main goals are:
Within the International Cell Exchange - 9 programs and International KIR Exchange:
|6 Shipments per year||Per Shipment|
|1. Cell Exchange - Class I Serology||4 lymphocyte preps|
|2. Cell Exchange - Class I DNA||4 cell preps|
|3. DNA Extract Exchange - Class I DNA||4 extracts|
|4. Serum Exchange - Class I Antibody Idenfitication||4 sera|
|5. B-Cell Exchange - Class II Serology||2 cell lines|
|6. B-Cell Exchange - Class I and II DNA||2 cell lines|
|3 Shipments per year|
|1. KIR Exchange||4 extracts|
|2. Mica Exchange||4 extracts|
|3. Virtual Crossmatch Exchange||2 cells/4sera|
Many laboratories use our programs to fulfill their external quality control needs. In 2006, over 200 laboratories throughout the world actively participated in our exchange programs. Nearly half of the participants were laboratories outside the United States, affirming that our Exchange is truly an international collaboration.
The acceptable allele and antigen names are the designations recognized by the WHO Nomenclature Committee. For lists of current HLA class I and class II allelges, please go to http://hla.alleles.org and click on "Alleles" at top of page.
For more information regarding HLA nomenclature changes, visit their website. The nomenclature changes will be officially introduced in April 2010. Lists of old and new allele names will be made available through the IMGT/HLA Database at http://www.ebi.ac.uk/imgt/hla and will be published in Tissue Antigens.