Identification of three new HLA-A intronic variants by next-generation sequencing.

Three novel HLA-A intronic variants, HLA-A*03:01:01:121, HLA-A*29:02:01:41 and HLA-A*30:02:01:24, detected by next-generation sequencing.

Characterisation of the novel HLA-C*01:262 allele by sequencing-based typing.

HLA-C*01:262 differs from HLA-C*01:02:01:01 by one nucleotide substitution in codon 150 in exon 3.

Characterisation of the HLA-DQ alpha eplet 52SK targeting the DQA1*01 alleles family.

Eplet 52SK is unique in the HLA eplet registry as targeting the whole family of DQA1*01 alleles. It is proposed as an antibody-verified eplet but has not been validated enough to deserve this label. Especially, confusion can occur with reactivity targeting the 52PQ eplet which is present on the DQB1*05 and DQB1*06 alleles families, as DQ molecule stability imposes DQA1*01 to selectively associate with these DQ-ß families only. Using two Luminex single antigen (LSA) assays from two vendors, beads bearing DR-α/DQ6 heterodimers, a special build LSA panel of additional DQ beads, and an adsorption/elution strategy relying on cells from deceased donors or recombinant cells solely expressing one DQ antigen, we definitely established the antibody-verified status of eplet 52SK using patients' sera reacting only against the DQ5 and DQ6 beads of the One Lambda LSA panel in routine patients' follow up. We also show that reactivity against this eplet is not a rare event among anti-DQ1 immunisation. This study further strengthens the importance of considering the DQA1 locus in immunological studies of HLA and in organ allocation strategies.

Detection of the HLA-B*40:78 allele in a Taiwanese individual.

One nucleotide substitution in codon 136 of HLA-B*40:02:01:01 results in a novel allele, HLA-B*40:78.

Characterization of the Novel HLA-C*07:01:126 Allele by Sequencing-Based Typing.

HLA-C*07:01:126 differs from HLA-C*07:01:01:01 by one nucleotide substitution in codon 328 in exon 7.

The HLA-C*14:152 Allele Was Identified Using a Next-Generation Sequencing Method.

HLA-C*14:152 differs from HLA-C*14:02:01:01 by a non-synonymous nucleotide substitution in exon 5.

Characterization of the Novel HLA-A*24:02:169 Allele by Sequencing-Based Typing.

HLA-A*24:02:169 differs from HLA-A*24:02:01:01 by one nucleotide substitution in codon -23 in exon 1.

Human leukocyte antigen compatibility and incidence of donor-specific antibodies in pediatric liver transplant recipients.

BACKGROUND: Antibody-mediated rejection following liver transplantation (LT) has been increasingly recognized, particularly with respect to the emergence of de novo donor-specific antibodies (DSAs) and their impact on graft longevity. While substantial evidence for adult populations exists, research focusing on pediatric LT outcomes remains limited. AIM: To investigate the prevalence of human leukocyte antigen (HLA) mismatches and DSA and evaluate their association with rejection episodes after pediatric LT. METHODS: A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre, Brazil, between December 2013 and December 2023. Only patients who survived for > 30 days after LT with at least one DSA analysis were included. DSA classes I and II and cross-matches were analyzed. The presence of de novo DSA (dnDSA) was evaluated at least 3 months after LT using the Luminex® single antigen bead method, with a positive reaction threshold set at 1000 MFI. Rejection episodes were confirmed by liver biopsy. RESULTS: Overall, 67 transplanted children were analyzed; 61 received grafts from living donors, 85% of whom were related to recipients. Pre-transplant DSA (class I or II) was detected in 28.3% of patients, and dnDSA was detected in 48.4%. The median time to DSA detection after LT was 19.7 [interquartile range (IQR): 4.3-35.6] months. Biopsy-proven rejection occurred in 13 patients at follow-up, with C4d positivity observed in 5/13 Liver biopsies. The median time to rejection was 7.8 (IQR: 5.7-12.8) months. The presence of dnDSA was significantly associated with rejection (36% vs 3%, P < 0.001). The rejection-free survival rates at 12 and 24 months were 76% vs 100% and 58% vs 95% for patients with dnDSA anti-DQ vs those without, respectively. CONCLUSION: Our findings highlight the importance of incorporating DSA assessment into pre- and post-transplantation protocols for pediatric LT recipients. Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.

Identification of the novel HLA-B*49:01:01:22 allele in an Indian renal transplant donor by next generation sequencing.

HLA-B*49:01:01:22 differs from HLA-B*49:01:01:01 by a single nucleotide C->G change in intron 5 at gDNA 2451.

Refining cPRA calculation to improve HLA compatibility assessment in organ transplantation: A detailed picture of the Paris waiting list.

The determination of panel reactive antibodies (cPRA) scores plays a critical role in assessing the immunological compatibility between organ transplant recipients and potential donors. Traditional cPRA methods focus on a limited number of HLA loci using physical cytotoxicity tests. However, advancements such as the Luminex single antigen (LSA) assay, which uses mean fluorescence intensity (MFI) of individualised HLA antigens for antibody evaluation, provide a foundation for a more precise assessment. We developed cPRAdictor, a novel cPRA calculation tool using a large series of HLA-type individuals in France with NGS. cPRAdictor was applied to a cohort of 5962 kidney transplant candidates in Paris. We analysed how extending the range of HLA specificities could affect cPRA values. Implementing cPRAdictor revealed and allowed quantification of the significant discrepancies in cPRA values that appeared when HLA loci C and DP, and antigen-specific antibodies were taken into account. Notably, over 43% of the immunised transplant candidates showed an increase in calculated cPRA values when considering C/DP loci and antigen-specific antibodies, negatively impacting their eligibility and prioritisation in the transplantation programme. These findings highlight the necessity of revisiting cPRA calculation methodologies to include a broader spectrum of immunological data, as more exhaustive and precise information regarding anti-HLA antibodies in patients' sera and donor and recipient HLA typing are available prospectively. This will strongly improve both accuracy and equity at the organ allocation step, especially for highly sensitised candidates for whom organ offers are very limited in number.

Characterisation of the novel HLA-DPA1*01:12:03 allele by sequencing-based typing.

HLA-DPA1*01:12:03 differs from HLA-DPA1*01:12:01 by one nucleotide substitution in codon 204 in exon 4.

Identification of nine novel HLA alleles by next-generation sequencing in individuals from India.

Nine novel HLA alleles were identified when HLA typing individuals from the Indian population.

Seven new HLA alleles characterised by next-generation sequencing.

Identification of seven new HLA alleles by next-generation sequencing.

A novel HLA-C*07 variant allele, HLA-C*07:01:01:141, identified by next-generation sequencing.

Characterisation of the novel HLA-C*07:01:01:141 allele in a 23-year-old Greek bone marrow donor.

Identification of the novel HLA-B*56:100 allele by next-generation sequencing.

HLA-B*56:100 differs from HLA-B*56:20:02 by one nucleotide substitution at codon 147.2 in exon 3.

Characterisation of the novel HLA-DPB1*04:02:24 allele by next-generation sequencing.

HLA-DPB1*04:02:24 differs from HLA-DPB1*04:02:01:01 by a single synonmous nucleotide substitution at position 639 G>A.

Identification of the novel HLA-C*08:291 allele by next-generation sequencing.

HLA-C*08:291, a novel HLA class I allele detected by next-generation sequencing.

Characterisation of the novel HLA-DQB1*05:305 allele using next-generation sequencing.

HLA-DQB1*05:305 shows one single nucleotide substitution at position 664 compared with HLA-DQB1*05:03:01:01.

Characterisation of the novel HLA-DRB3*02:202 allele by sequencing-based typing.

HLA-DRB3*02:202 differs from DRB3*02:112 by one nucleotide substitution in codon 51 in exon 2.

Characterisation of the novel HLA-A*26:247 allele by sequencing-based typing.

HLA-A*26:247 differs from HLA-A*26:01:01:01 by one nucleotide substitution in codon 245 in exon 4.