Characterization of the novel HLA-B*49:39 allele identified in a German leukaemia patient

HLA ‐ B*49:39 allele is characterised by 1 amino acid substitution in the alpha 1 domain.

hematopoietic stem cell transplantation; HLA ‐ B*49; human leukocyte antigen ‐ B; mismatched related donor; sequence ‐ based typing

Currently, 12   021 human leukocyte antigen (HLA) class I alleles are cited at hla.alleles.org (assigned as of January 2017), including 4647 HLA ‐ B alleles with 55 belonging to the HLA ‐ B*49 group.[1] Here, we present the identification of the novel HLA ‐ B*49:39 allele found in a Caucasian leukaemia patient transplanted from his HLA 9 of 10 matched daughter.

The HLA ‐ B high ‐ resolution typing of a patient performed by sequence ‐ based typing (AlleleSEQR HLA ‐ B Sequencing Kit, Abbott, Wiesbaden) showed the presence of HLA ‐ B*44:02:01:01,*49:01:01/49:01:04 with 1 coding nucleotide difference in exon 2 in one of the alleles (ABI Prism 3730xl Genetic Analyzer, Applied Biosystems, Waltham, MA; sequence analysis with Sequence Pilot Software, JSI medical systems GmbH). In order to find a potentially related stem cell donor, patient's sister and 2 children were analysed by HLA high ‐ resolution typing. The HLA ‐ B analysis resulted in HLA ‐ B*13:02,*44:02 for the sister, and HLA ‐ B*44:02:01:01,*NEW for daughter 1, and HLA ‐ B*44:03:01,*NEW for daughter 2. Both novel alleles were similar to HLA ‐ B*49:01:01 with the same coding nucleotide difference in exon 2 as for the patient. The HLA sequence analysis of the patient's family members including HLA ‐ B of patient's wife in addition to HLA ‐ A, ‐ C, ‐ DRB1 and ‐ DQB1 by sequence ‐ specific oligonucleotide (SSO) (HISTO SPOT SSO, BAG Health Care, Lich, Germany) defined the inheritance of the novel HLA ‐ B*49:39 allele on haplotype HLA ‐ A*03:01~C*07:01~, B*49:39~DRB1*01:01~DQB1*05:04 (Figure [NaN] ).

In comparison to the nearest related allele HLA ‐ B*49:01:01, the novel HLA ‐ B*49:39 allele is characterised by 1 nucleotide substitution at position 236 where adenosine is exchanged by guanine (exon 2, codon 55, GAG to GGG).[2] This exchange leads to an amino acid change from glutamine acid to glycine. A dissimilation score proposed by Risler et al of 47 shows a moderate dissimilarity of the novel HLA ‐ B*49:39 compared with the HLA ‐ B*49:01:01 encoded protein.[3] The amino acid exchange of HLA ‐ B*49:01:01 is located in the alpha 1 structural domain of the mature protein. This amino acid is not involved in the binding of presented peptides and the exchange should have a minor relevance for the functionality in peptide presentation.[2] As the amino acid at this position is not part of epitopes known to be characterised by B49, the mature protein of the novel allele may show a similar serologic reaction as the HLA ‐ B49.[4] Indeed, the serologic typing of the patients cells resulted in B44, 49.

The nucleotide sequence data of HLA ‐ B*49:39 has been submitted to EMBL (LN833603) and the IPD ‐ IMGT/HLA Database (HWS10025252). The name HLA ‐ B*49:39 has been officially assigned by the World Health Organization (WHO) Nomenclature Committee for Factors of the HLA System in April 2015 and made public in IPD ‐ IMGT/HLA Database Release 3.21.0. This follows the agreed policy that, subject to the conditions stated in the most recent Nomenclature Report, names will be assigned to new sequences as they are identified.[5] Lists of such new names will be published in the following WHO Nomenclature Report.

We are very grateful to Anja Goodwin for her excellent technical assistance.

The authors have declared no conflicting interests.

Graph: Shown is the family tree and segregation analysis of the novel HLA ‐ B*49:39 allele. Results are based on sequence ‐ based typing of family members (sister, 2 daughters and human leukocyte antigen (HLA) ‐ B of wife), and sequence ‐ specific oligonucleotide (SSO) of patient's wife, respectively. Bold letters represents the haplotype of the novel allele. Grey boxes represent family members carrying the novel HLA ‐ B*49:39 allele