Steve Spellman - Center for International Blood and … · Steve Spellman Sr. Manager, NMDP ... Incoming ---- Outgoing Paper ---- Electronic ... with global partners and disseminate

HLA Nomenclature 3 0HLA Nomenclature 3.0

Steve SpellmanSr. Manager, NMDPAsst. Scientific Director, CIBMTR

What is Nomenclature?

Differences outside the

What is Nomenclature?

HLA A * 24 02 01 02 L

Signifies DNA Subtypee e ces outs de t e

coding region (introns)

HLA-A * 24 02 01 02 LLocus Type Silent ExpressionLocus Type Silent

SubstitutionExpression

Corresponds to the to the

serologic antigen or

family

NATIONAL MARROW DONOR PROGRAM®

Entrusted to operate the C.W. Bill Young Cell Transplantation Program, including the Be The Match RegistrySM 2

Number of new alleles discovered 1987 - 2009

Class I Alleles

Class II AllelesClass II Alleles



In 2002, 2 types In 2002, 2 types exceeded 99 alleles

A*0299 A*9201A 0299 A 9201B*1599 B*9501

Called Rollovers



In 2008, it was estimated that15 more types will need rollovers ~15 more types will need rollovers

(exceed 99)

A B C DPB1 DRB192 07 03 99 0492 07 03 99 0424 35 07 11

40 1340 1344 14515195



WHO HLA Nomenclature Changes

• Expand all HLA allele names

• Eliminate the “W” from HLA-C alleles

Create codes for ambiguous HLA allele • 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



binding domains P

HLA Nomenclature: Allele NamesStarting with the April 2010 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 variantyp ub yp y o y ou a a o a a

A*2405 24:05A*68020102 68:02:01:02A 68020102 68:02:01:02

– These groups will be expanded to 3 digits as necessary

– These groups will not be contracted below 2 digits



HLA Nomenclature: Allele Names

Don’t add any more unnecessary zeros

A*24:05

Keep the unnecessary zeros you’ve already got

A 24:05A*68:02:01:02

DPB1*109:01A*02:132A*02:01:116B*15 01 01 166B*15:01:01:166



A*02 Rollovers Roll BackA 02 Rollovers Roll Back

A*02:100A*9201 A*02:101A*9202 A*02:102A*9203 A*02:103A*9204 A*02:104A*9205 A*02:105A*9206 A*02:106...



B*15 Rollovers Roll BackB 15 Rollovers Roll Back

B*15:100B*9501 B*15:101B*9502 B*15:102B*9503 B*15:103B*9504 B*15:104B 9504 B 15:104B*9505 B*15:105B*9506 B*15:106B 9506 B 15:106…



DPB1 Group OverflowDPB1 Group Overflow

DPB1*010101 DPB1*01:01:01DPB1*020102 DPB1*02:01:02 DPB1*020102 DPB1*02:01:02 DPB1*0202 DPB1*02:02DPB1*030101 DPB1*03:01:01…

DPB1*9901 DPB1*99:01…

DPB1*0102 DPB1*100:01DPB1*0203 DPB1*101:01DPB1*0203 DPB1*101:01DPB1*0302 DPB1*102:01DPB1*0403 DPB1*103:01…



…

Rename HLA-CRename HLA CCw*010201 C*01:02:01Cw*010202 C*01:02:02Cw 010202 C 01:02:02Cw*010203 C*01:02:03Cw*010204 C*01:02:04Cw*010205 C*01:02:05…Cw*0103 C*01:03Cw*0104 C*01:04C *0105 C*01 05Cw*0105 C*01:05Cw*0106 C*01:06…



New G codesNew G codesHLA alleles that have identical nucleotide sequences across the exons encoding the peptide binding domains across the exons encoding the peptide binding domains (exon 2 and 3 for HLA class I and exon 2 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 numbered allele in the group.

A*02:01:01G =A*02:01:01:01/02:01:01:02L/02:01:01:03/02:01:08/02:01:11/02:01:14/02:01:15/02:01:21/02:09/02:43N/02:66/02:75/02:83N/02:89/02:97/02:132/02:134/02:140



New G CodesNew G Codes

Groove-Domain Cytoplasmic TailTM

Cl IClass I

Class II

1 5 6 87Exon 4Exon 3Exon 2

1 4 65Exon 3Exon 2

Identical DNA = GIdentical DNA G

New P codesNew P codesHLA alleles having nucleotide sequences that encode the same protein sequence for the peptide binding the same protein sequence for the peptide binding domains will be designated by an upper case ‘P’

A*02 01P A*02:01P= A*02:01:01:01/02:01:01:02L/02:01:01:03/02:01:02/02:01:03/02:01:04/02:01:05/02:01:06/02:01:07/02:01:08/02:01:09/02:01:10/02:01:11/02:01:12/02:01:13/02:01:14/02:01:15/02:01:17/02:01:18/02:01:19/02:01:02:01:17/02:01:18/02:01:19/02:01:21/02:01:22/02:09/02:66/02:75/02:89/02:97/02:132/02:134/02:140



New P Codes

Identical Protein = P

Multiple Allele Code PlanMultiple 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*0101/0102 and A*01:01/01:02A 0101/0102 and A 01:01/01:02

Very quickly all HLA typing will require v3 codesVery quickly all HLA typing will require v3 codes



Overview/ImplementationOverview/Implementation

All users of HLA worldwide will be impacted

• Related and unrelated transplant programs

• Solid organ transplant• Solid organ transplant

• Clinical and research labs

• Registries and cord blood banks

• Donor centers and blood banks

• Data collection centers



Transition PlanTransition Plan

Worldwide Cooperation

• NMDP Histocompatibility Advisory Group already working with ASHI and EFI representationworking with ASHI and EFI representation

• ASHI membership informed November 09 in San FranciscoFrancisco

• HLA vendor meeting November 09 in San Francisco

WMDA i t i d d bl d b k t ti • WMDA registries and cord blood bank representatives met in Sweden in March 09 and in Minneapolis November 09



Transition PlanTransition Plan

Some examples of places to expect changes:

Search Reports

P pe Repo tPaper Reports

Lab Reports

Forms

FormsNet



Pre-Transplant Essential DataPre Transplant Essential Data


Entrusted to operate the C.W. Bill Young Cell Transplantation Program, including the Be The Match RegistrySM 22BMT-Tandem09_2.ppt

Pre-TED examples pLab report

02:ANGA 44:02 03:BPSK 04:0703:XKS 55:01 07:ET 15:01

02:ANGA 44:AMUT 03:BPSK 04:07

03:0106:02

03:0202:ANGA 44:AMUT 03:BPSK 04:0703:XKS 55:01 05:AC 15:01 06:02

Pre-TED

0 0 1

0 1 ND


Entrusted to operate the C.W. Bill Young Cell Transplantation Program, including the Be The Match RegistrySM 23BMT-Tandem09_21.ppt

Form 2005Form 2005Current version

Updated version



Nomenclature 3.0 Data Entry Lab report

CUMULATIVE HLA TYPE RESULTS C #2C #1DR#2DR#1Bw #2Bw #1B #2B #1A #2A #1

DRB345 #2DRB345 #1DQ #2DQ #1

07:02

07:01

11:0103:0108:0107:0232:01/04/05

02:01/02/03

NT03:0102:01

Form 2005

02:01/02/03

32:01/04/05



32:01/04/05

What can you do?What can you do?

Think about the workflow of HLA information in your organization:

Start ---- FinishStart Finish

Incoming ---- Outgoing

Paper ---- Electronic

Systems ---- Databases



C i i hCommunicate with:

Y t bYour team members

Your IT staffYour 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

http://hla.alleles.org/announcement.html

http://bioinformatics.nmdp.org/HLA/Ver3_Nomenclature_Allele_Codes/index.html



AcknowledgementsAcknowledgements

• Michelle Setterholm NMDP

• Judy Davis NMDP

• Martin Maiers NMDP

• Steven Marsh Anthony Nolan Trust• 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: 612/617-8334 sspellma@nmdp [email protected] Brown: [email protected]



g

BMT-Tandem09_24.ppt

Documents

Steve Spellman - Center for International Blood and … · Steve Spellman Sr. Manager, NMDP ... Incoming ---- Outgoing Paper ---- Electronic ... with global partners and disseminate