The novel HLA-B*39:93 allele was identified by sequence-based typing in a French family V. Elsermans, I. Top, O. Farchi, P. Varlet & M. Labalette Institute of Immunology-HLA, CHRU Lille, Lille, France Key words: HLA-B*39:93; new allele; sequence-based typing
A novel HLA-B allele, B*39:93, was identified in a French family. Allogeneic hematopoietic stem cell transplantation (HSCT) is one of the treatment options for hematological malignancies. Donor/recipient compatibility within human leukocyte antigen (HLA) system is of primary importance for engraftment, prevention of graft vs host disease and overall survival. Siblings are commonly investigated in order to find an HLA identical hematopoietic stem cell (HSC) donor, actually considered as the best HSC source (1). For hematological patients in our transplant center, a first HLA typing by Luminex reverse sequence-specific oligonucleotide is usually performed (OneLambda Labtype HD, Los Angeles, CA). A patient suffering from multiple myeloma was eligible to an HSCT procedure. She was typed as B*39 by Luminex, B*39:01:01:01 being the most probable allele. Her brother was proved to be phenotypically identical. However, due to the lack of other family members, genotypical identity could not be assumed. Therefore, HLA sequence-based typing (SBT) was performed for both individuals. We used DNA sequencing reagents provided by Protrans (Protrans S4 mono allelic SBT kits, Hockenheim, Germany) run on the ABI 3730xl
(Applied Biosystems, Foster City, CA). Data were analyzed with SEQPILOT software (JSI Medical Systems). The patient and her brother were found to have a new B*39 allele and were consequently typed A*02:01:01G,*32:01:01; B*39:new,*53:01:01; C*04:01:01G,*12:03:01G; DRB1*11: 01:01G,*13:02:01; DQB1*03:01:01G,*05:01:01G. Sequencing was performed in both directions (forward and reverse) for exons 2, 3 and 4, two times with different polymerase chain reaction products. Results were each time identical. Interestingly, serological typing by complement-dependent cytotoxicity clearly stated that this new HLA-B allele is expressed at cell surface. Monoclonal sera with B16, B39 and Bw6 specificities reacted with the patient’s cells (Lambda Monoclonal Typing Tray Set Class I, OneLambda, Los Angeles, CA). Using IMGT/HLA database (2), nucleotide sequence alignment with HLA-B alleles shows that this new allele has one nucleotide change from B*39:01:01:01 at nucleotide 221 of exon 2, where C → T resulting in a new protein (codon 74 CCG → CTG, Pro → Leu, Figure 1). The nucleotide sequence is available at European Nucleotide Archive accession number LM994935. The name B*39:93 has been officially assigned by the World Health Organization (WHO) Nomenclature Committee in April 2014. This follows
Figure 1 Alignment of the sequence of exon 2 of B*39:93 with the sequence of B*39:01:01:01. Dashes indicate nucleotide identity between the two alleles. Numbers above the sequence indicate codon position.
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© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Tissue Antigens, 2015, 85, 132–154
the agreed policy that, subject to the conditions stated in the most recent Nomenclature Report (3), names will be assigned to new sequences as they are identified. Lists of such new names will be published in the following WHO Nomenclature Report.
Conflicts of interest
Correspondence
1. Alousi AM, Le-Rademacher J, Saliba RM et al. Who is the better donor for older hematopoietic transplant recipients: an older-aged sibling or a young, matched unrelated volunteer? Blood 2013: 121: 2567–73. 2. Robinson J, Halliwell JA, McWilliam H, Lopez R, Parham P, Marsh SGE. The IMGT/HLA database. Nucleic Acids Res 2012: 41: D1222–7. 3. Marsh SGE, Albert ED, Bodmer WF et al. Nomenclature for factors of the HLA system. Tissue Antigens 2010: 75: 291–455.
Vincent Elsermans Institute of Immunology-HLA CHRU Lille Lille France Tel: +33 320445408 Fax: +33 320444389 e-mail: [email protected]
The authors have declared no conflicting interests. References
doi: 10.1111/tan.12508
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Tissue Antigens, 2015, 85, 132–154
145
Copyright of Tissue Antigens is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
A novel HLA-B allele, B*39:93, was identified in a French family. Allogeneic hematopoietic stem cell transplantation (HSCT) is one of the treatment options for hematological malignancies. Donor/recipient compatibility within human leukocyte antigen (HLA) system is of primary importance for engraftment, prevention of graft vs host disease and overall survival. Siblings are commonly investigated in order to find an HLA identical hematopoietic stem cell (HSC) donor, actually considered as the best HSC source (1). For hematological patients in our transplant center, a first HLA typing by Luminex reverse sequence-specific oligonucleotide is usually performed (OneLambda Labtype HD, Los Angeles, CA). A patient suffering from multiple myeloma was eligible to an HSCT procedure. She was typed as B*39 by Luminex, B*39:01:01:01 being the most probable allele. Her brother was proved to be phenotypically identical. However, due to the lack of other family members, genotypical identity could not be assumed. Therefore, HLA sequence-based typing (SBT) was performed for both individuals. We used DNA sequencing reagents provided by Protrans (Protrans S4 mono allelic SBT kits, Hockenheim, Germany) run on the ABI 3730xl
(Applied Biosystems, Foster City, CA). Data were analyzed with SEQPILOT software (JSI Medical Systems). The patient and her brother were found to have a new B*39 allele and were consequently typed A*02:01:01G,*32:01:01; B*39:new,*53:01:01; C*04:01:01G,*12:03:01G; DRB1*11: 01:01G,*13:02:01; DQB1*03:01:01G,*05:01:01G. Sequencing was performed in both directions (forward and reverse) for exons 2, 3 and 4, two times with different polymerase chain reaction products. Results were each time identical. Interestingly, serological typing by complement-dependent cytotoxicity clearly stated that this new HLA-B allele is expressed at cell surface. Monoclonal sera with B16, B39 and Bw6 specificities reacted with the patient’s cells (Lambda Monoclonal Typing Tray Set Class I, OneLambda, Los Angeles, CA). Using IMGT/HLA database (2), nucleotide sequence alignment with HLA-B alleles shows that this new allele has one nucleotide change from B*39:01:01:01 at nucleotide 221 of exon 2, where C → T resulting in a new protein (codon 74 CCG → CTG, Pro → Leu, Figure 1). The nucleotide sequence is available at European Nucleotide Archive accession number LM994935. The name B*39:93 has been officially assigned by the World Health Organization (WHO) Nomenclature Committee in April 2014. This follows
Figure 1 Alignment of the sequence of exon 2 of B*39:93 with the sequence of B*39:01:01:01. Dashes indicate nucleotide identity between the two alleles. Numbers above the sequence indicate codon position.
144
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Tissue Antigens, 2015, 85, 132–154
the agreed policy that, subject to the conditions stated in the most recent Nomenclature Report (3), names will be assigned to new sequences as they are identified. Lists of such new names will be published in the following WHO Nomenclature Report.
Conflicts of interest
Correspondence
1. Alousi AM, Le-Rademacher J, Saliba RM et al. Who is the better donor for older hematopoietic transplant recipients: an older-aged sibling or a young, matched unrelated volunteer? Blood 2013: 121: 2567–73. 2. Robinson J, Halliwell JA, McWilliam H, Lopez R, Parham P, Marsh SGE. The IMGT/HLA database. Nucleic Acids Res 2012: 41: D1222–7. 3. Marsh SGE, Albert ED, Bodmer WF et al. Nomenclature for factors of the HLA system. Tissue Antigens 2010: 75: 291–455.
Vincent Elsermans Institute of Immunology-HLA CHRU Lille Lille France Tel: +33 320445408 Fax: +33 320444389 e-mail: [email protected]
The authors have declared no conflicting interests. References
doi: 10.1111/tan.12508
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Tissue Antigens, 2015, 85, 132–154
145
Copyright of Tissue Antigens is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
