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 two HLA-B*35 variants: HLA-B*35:01:01:39 and -B*35:03:01:32.

Two nucleotide substitutions in intronic regions give rise to the novel alleles: HLA-B*35:01:01:39 and -B*35:03:01:32.

Next-generation sequencing identifies four novel HLA class I alleles with nucleotide substitutions in the 3' UTR.

Characterization by next-generation sequencing of four novel HLA alleles: C*17:03:01:07, C*16:01:01:39, B*15:17:01:07, and B*44:03:01:57.

Characterization of the first HLA-DQA1 allele with Aspartic Acid in the transmembrane domain, HLA-DQA1*05:71.

HLA-DQA1*05:71, the first HLA-DQA1 allele with Aspartic Acid at residue 208 in the transmembrane domain.

The novel HLA-DQB1*03:02:01:14 allele was possibly generated by a recombination event.

The novel HLA-DQB1*03:02:01:14 was likely generated by a recombination event between DQB1*03:02:01:01 and DQB1*03:03:02:01.

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*02:01:09:01 allele by two different next-generation sequencing platforms.

A synonymous nucleotide substitution in exon 3 results in the novel HLA-DQA1*02:01:09:01 allele.