HLA-A * L

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1 What is Nomenclature? HLA Nomenclature 3.0 Signifies DNA Subtype Differences outside the coding region (introns) HLA-A * L Steve Spellman Sr. Manager, NMDP Asst. Scientific Director, CIBMTR Locus Type Silent Substitution Corresponds to the serologic antigen or family Expression Number of new alleles discovered Class I Alleles Class II Alleles In 00, types exceeded 99 alleles A*099 A*901 B*1599 B*9501 Called Rollovers 3 4 In 008, it was estimated that ~15 more types will need rollovers (exceed 99) A B C DPB1 DRB WHO HLA Nomenclature Changes Expand all HLA allele names Eliminate the W from HLA-C alleles Create codes for ambiguous HLA allele typings HLA alleles that encode for identical peptide binding domains =G HLA alleles that share identical nucleotide sequences for the exons encoding the peptide binding domains =P 5 6 1

2 HLA Nomenclature: Allele Names Starting with the April 010 update (HLADB-3.0.0) the following changes will be made to accommodate the allele growth: A delimiter (colon) will be introduced between: type : subtype : synonymous variant : intron variant A*405 4:05 A* :0:01:0 These groups will be expanded to 3 digits as necessary These groups will not be contracted below digits HLA Nomenclature: Allele Names Don t add any more unnecessary zeros Keep the unnecessary zeros you ve already got A*4:05 A*68:0:01:0 DPB1*109:01 A*0:13 A*0:01:116 B*15:01:01: A*0 Rollovers Roll Back A*0:100 A*901 A*0:101 A*90 A*0:10 A*903 A*0:103 A*904 A*0:104 A*905 A*0:105 A*906 A*0: B*15 Rollovers Roll Back B*15:100 B*9501 B*15:101 B*950 B*15:10 B*9503 B*15:103 B*9504 B*15:104 B*9505 B*15:105 B*9506 B*15: DPB1 Group Overflow DPB1* DPB1*01:01:01 DPB1*0010 DPB1*0:01:0 DPB1*00 DPB1*0:0 DPB1* DPB1*03:01:01 DPB1*9901 DPB1*99:01 DPB1*010 DPB1*100:01 DPB1*003 DPB1*101:01 DPB1*030 DPB1*10:01 DPB1*0403 DPB1*103:01 Rename HLA-C Cw*01001 C*01:0:01 Cw*0100 C*01:0:0 Cw*01003 C*01:0:03 Cw*01004 C*01:0:04 Cw*01005 C*01:0:05 Cw*0103 C*01:03 Cw*0104 C*01:04 Cw*0105 C*01:05 Cw*0106 C*01:

3 New G codes HLA alleles that have identical nucleotide sequences across the exons encoding the peptide binding domains (exon and 3 for HLA class I and exon only for HLA class II alleles) will be designated by an upper case G which follows the allele designation of the lowest numbered allele in the group. A*0:01:01G = A*0:01:01:01/0:01:01:0L/0:01:01:03/0:01:08/0:01:11 /0:01:14/0:01:15/0:01:1/0:09/0:43N/0:66/0:75/0: 83N/0:89/0:97/0:13/0:134/0:140 New G Codes Groove-Domain TM Cytoplasmic Tail Class I 1 Exon Exon 3 Exon Class II 1 Exon Exon Identical DNA = G 13 New P codes HLA alleles having nucleotide sequences that encode the same protein sequence for the peptide binding domains will be designated by an upper case P New P Codes Identical Protein = P A*0:01P= A*0:01:01:01/0:01:01:0L/0:01: 01:03/0:01:0/0:01:03/0:01:04/ 0:01:05/0:01:06/0:01:07/0:01: 08/0:01:09/0:01:10/0:01:11/0: 01:1/0:01:13/0:01:14/0:01:15/ 0:01:17/0:01:18/0:01:19/0:01: 1/0:01:/0:09/0:66/0:75/0: 89/0:97/0:13/0:134/0: Multiple Allele Code Plan Position entire code after first delimiter A*01:AB or A*01:ABCD Distribute codes in both old and new format A*0101/010 and A*01:01/01:0 Very quickly all HLA typing will require v3 codes Overview/Implementation All users of HLA worldwide will be impacted Related and unrelated transplant programs Solid organ transplant Clinical i l and research labs Registries and cord blood banks Donor centers and blood banks Data collection centers

4 Transition Plan Worldwide Cooperation NMDP Histocompatibility Advisory Group already working with ASHI and EFI representation ASHI membership informed November 09 in San Francisco HLA vendor meeting November 09 in San Francisco WMDA registries and cord blood bank representatives met in Sweden in March 09 and in Minneapolis November 09 Transition Plan Some examples of places to expect changes: Search Reports Paper Reports Lab Reports Forms FormsNet 19 0 Pre-Transplant Essential Data BMT-Tandem09_.ppt Lab report Pre-TED examples Current version Form 005 0:ANGA 44:0 03:BPSK 04:07 03:XKS 55:01 07:ET 15:01 0:ANGA 44:AMUT 03:BPSK 04:07 03:XKS 55:01 05:AC 15:01 03:01 06:0 03:0 06:0 Pre-TED Updated version ND 3 BMT-Tandem09_1.ppt 4 4

5 Nomenclature 3.0 Data Entry Lab report A #1 A # B #1 B # CUMULATIVE Bw #1 Bw HLA # TYPE RESULTS DR#1 DR# C #1 C# 0:01/0 /03 3:01/ 04/05 07:0 08:01 03:01 11:01 07:0 1 07:0 DQ #1 DQ # DRB345 #1 DRB345 # 0:01 03:01 NT Form 005 0:01/0/03 What can you do? Think about the workflow of HLA information in your organization: Start ---- Finish Incoming ---- Outgoing Paper ---- Electronic Systems ---- Databases 3:01/04/ Communicate with: Your team members Your IT staff Your vendors Your partners Your HLA experts NMDP will continue to collaborate with global partners and disseminate information Web site for more information omenclature_allele_codes/index.html 7 8 Acknowledgements Michelle Setterholm NMDP Judy Davis NMDP Martin Maiers NMDP Steven Marsh Anthony Nolan Trust WHO Nomenclature Committee for Factors of the HLA System Please remember: If you have any questions, please contact: Steve Spellman: 61/ sspellma@nmdp.org Maria Brown: mbrown@nmdp.org 9 30 BMT-Tandem09_4.ppt 5

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