Quantifying HLA Mismatches at Epitope Level in Haplo-HSCT: Impact in the Outcome in Strategies Using PTCy.

Haploidentical haematopoietic stem cell transplantation (haplo-HSCT) is one of the most effective therapies for treating malignant haematological disorders. However, HLA disparities are significant barriers to the success of this process since they increase the risk of graft versus host disease (GvHD). HLA disparities quantification could help to anticipate the probability and degree of GvHD, but the best tool for such quantification remains a challenge.

Detection of the novel HLA-DQA1*05:73 allele with an amino acid substitution in the α2 extracellular domain.

A single nucleotide substitution in the exon 3 gives rise to the novel HLA-DQA1*05:73 allele.

Discovery of three HLA-DQB1*03:01:01 variants: HLA-DQB1*03:01:01:54, -DQB1*03:01:01:56 and -DQB1*03:01:01:58.

Three nucleotide substitutions in intronic regions give rise to the novel alleles: HLA-DQB1*03:01:01:54, -DQB1*03:01:01:56, -DQB1*03:01:01:58.

HLA-DPA1*02:01:25, a novel allele with a synonymous transition in exon 2 identified by next-generation sequencing.

HLA-DPA1*02:01:25 differs from DPA1*02:01:01:02 by a synonymous transition in exon 2.

A missense substitution in exon 1 generates the first HLA-DRB1 allele with Valine at residue -17, DRB1*04:354.

A missense nucleotide substitution in codon -17 in the leader peptide results in the novel HLA-DRB1*04:354 allele.

Detection and characterization of the novel HLA-DPA1*02:66:02N allele, with a premature stop codon in exon 2.

The failure to identify HLA null alleles in bone marrow transplantation could be life-threatening because this could result in an HLA mismatch with the ability to trigger the graft-vs-host disease (GVHD) and to reduce patient's survival. In this report we describe the identification and characterization of the novel HLA-DPA1*02:66:02N allele with a non-sense codon in exon 2. This new allele was discovered in two unrelated bone marrow donors during routine HLA-typing using next-generation sequencing (NGS).

Identification of the novel HLA-DQA1*01:04:07 allele with a synonymous substitution and an intronic insertion.

A synonymous substitution in exon 2 and intronic insertion results in the novel HLA-DQA1*01:04:07 allele.