Publications by authors named "Marco Andreani"

79 Publications

HLA-haploidentical TCRαβ+/CD19+-depleted stem cell transplantation in children and young adults with Fanconi anemia.

Blood Adv 2021 Mar;5(5):1333-1339

Department of Pediatric Hemato-Oncology and Cell and Gene Therapy, Scientific Institute for Research and Healthcare (IRCCS) Bambino Gesù Children's Hospital, Rome, Italy.

We report on the outcome of 24 patients with Fanconi anemia (FA) lacking an HLA matched related or unrelated donor, given an HLA-haploidentical T-cell receptor αβ (TCRαβ+) and CD19+ cell-depleted hematopoietic stem cell transplantation (HSCT) in the context of a prospective, single-center phase 2 trial. Sustained primary engraftment was achieved in 22 (91.6%) of 24 patients, with median time to neutrophil recovery of 12 days (range, 9-15 days) and platelet recovery of 10 days (range, 7-14 days). Cumulative incidences of grade 1 to 2 acute graft-versus-host disease (GVHD) and chronic GVHD were 17.4% (95% confidence interval [CI], 5.5%-35.5%) and 5.5% (95% CI, 0.8%-33.4%), respectively. The conditioning regimen, which included fludarabine, low-dose cyclophosphamide and, in most patients, single-dose irradiation was well tolerated; no fatal transplant-related toxicity was observed. With a median follow-up of 5.2 years (range, 0.3-8.7 years), the overall and event-free survival probabilities were 100% and 86.3% (95% CI, 62.8%-95.4%), respectively (2 graft failures and 1 case of poor graft function were considered as events). The 2 patients who experienced primary graft failure underwent a subsequent successful HSCT from the other parent. This is the first report of FA patients given TCRαβ+/CD19+-depleted haplo-HSCT in the context of a prospective trial, and the largest series of T-cell-depleted haplo-HSCT in FA reported to date. This trial was registered at www.clinicaltrials.gov as #NCT01810120.
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http://dx.doi.org/10.1182/bloodadvances.2020003707DOI Listing
March 2021

Identification of the novel HLA-DPB1*1149:01.

HLA 2021 Feb 10. Epub 2021 Feb 10.

Laboratory of Immunogenetics and Transplant, Department of Oncohematology and Cell and Gene Therapy, IRCCS Bambin Gesù Pediatric Hospital, Rome, Italy.

The new allele HLA-DPB1*1149:01 differs from HLA-DPB1*09:01:01 by one nucleotide substitution in Exon 4.
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http://dx.doi.org/10.1111/tan.14212DOI Listing
February 2021

Characterization of the novel HLA-DRB3*03:49 allele by sequencing-based typing.

HLA 2021 Feb 10. Epub 2021 Feb 10.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Bordeaux, France.

HLA-DRB3*03:49 differs from DRB3*03:01:01:01 by one nucleotide substitution in codon 191 in exon 4.
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http://dx.doi.org/10.1111/tan.14211DOI Listing
February 2021

Characterization of the novel HLA-DPA1*01:44 allele by sequencing-based typing.

HLA 2021 Feb 9. Epub 2021 Feb 9.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Place Amélie Raba Léon, Bordeaux, France.

HLA-DPA1*01:44 differs from DPA1*01:03:01:04 by one nucleotide substitution in codon 175 in exon 3.
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http://dx.doi.org/10.1111/tan.14208DOI Listing
February 2021

and other HLA-C alleles, as well as and genetic variants associate with optimal response to anti-IL-17A treatment in patients with psoriasis.

Expert Opin Biol Ther 2021 Feb 28;21(2):259-270. Epub 2020 Dec 28.

Laboratory of Experimental Immunology, IDI-IRCCS , Rome, Italy.

: Our pharmacogenomic study evaluated the influence of the presence/absence of genetic variants of psoriasis-risk loci on the clinical response to secukinumab. Differences in the single-nucleotide polymorphism (SNP) pattern characterizing HLA-Cw6 or HLA-Cw6 patient subpopulations, showing high or low responses to secukinumab, were also analyzed. : 417 SNPs were analyzed by Next-Generation Sequencing technology, in a cohort of 62 psoriatic patients and undergone secukinumab treatment. Univariate regression analysis was employed to examine the association between SNP and clinical response to secukinumab. Multivariate analysis was also performed to assess multivariate differences in SNP pattern of HLA-Cw6 or HLA-Cw6 patients showing high or low responses to secukinumab. : Eight SNPs in and upstream region (rs13207315, rs6900444, rs12189871, rs12191877, rs4406273, and rs10484554), including classical allele (rs1131118), and three in (rs9267325), (rs34085293) and (rs2304255) genes, associating with excellent response to secukinumab were identified. Importantly, rs34085293 or s2304255 SNP status defined a subgroup of super-responder patients. We also found that HLA-Cw6 and HLA-Cw6 patients carried out specific patterns of SNPs associating with different responses to secukinumab. : Assessment of , together with other allelic variants of genes, could be helpful to define patients which better benefit from anti-IL-17 therapy. PASI: Psoriasis Area and Severity Index; SNP: Single-Nucleotide Polymorphism Rs: Reference SNP; PASI75: 75% reduction in Psoriasis Area and Severity Index; PASI90: 90% reduction in Psoriasis Area and Severity Index; PASI100: 100% reduction in Psoriasis Area and Severity Index; NGS: Next-Generation Sequencing; OR: Odds Ratio; CAP: Canonical Analysis of Principal coordinates; BMI: Body Mass Index; LD: Linkage Disequilibrium.
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http://dx.doi.org/10.1080/14712598.2021.1862082DOI Listing
February 2021

Characterization of the novel HLA-DPA1*01:42 allele by sequencing-based typing.

HLA 2021 Jan 12;97(1):93-94. Epub 2020 Nov 12.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Place Amélie Raba Léon, Bordeaux, France.

HLA-DPA1*01:42 differs from DPA1*01:03:01:02 by one nucleotide substitution in Codon 76 in Exon 2.
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http://dx.doi.org/10.1111/tan.14130DOI Listing
January 2021

HLA allele frequencies and susceptibility to COVID-19 in a group of 99 Italian patients.

HLA 2020 11 3;96(5):610-614. Epub 2020 Sep 3.

Department of Haematology and Oncology, Bambino Gesù Children's Hospital, IRCCS, Rome.

With the aim to individuate alleles that may reflect a higher susceptibility to the disease, in the present study we analyzed the HLA allele frequency distribution in a group of 99 Italian patients affected by a severe or extremely severe form of COVID-19. After the application of Bonferroni's correction for multiple tests, a significant association was found for HLA-DRB1*15:01, -DQB1*06:02 and -B*27:07, after comparing the results to a reference group of 1017 Italian individuals, previously typed in our laboratory. The increased frequencies observed may contribute to identify potential markers of susceptibility to the disease, although controversial results on the role of single HLA alleles in COVID-19 patients have been recently reported.
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http://dx.doi.org/10.1111/tan.14047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461491PMC
November 2020

Characterization of the novel HLA-DRB3*01:86 allele by sequencing-based typing.

HLA 2020 Oct 21;96(4):535-537. Epub 2020 Aug 21.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Place Amélie Raba Léon, Bordeaux, France.

HLA-DRB3*01:86 differs from HLA-DRB3*01:01:02:01 by one nucleotide substitution in codon 225 in exon 4.
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http://dx.doi.org/10.1111/tan.14018DOI Listing
October 2020

Characterization of the novel HLA-DQA1*01:48 allele by sequencing-based typing.

HLA 2020 Sep 15;96(3):362-364. Epub 2020 Jun 15.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Place Amélie Raba Léon, Bordeaux, France.

HLA-DQA1*01:48 differs from HLA-DQA1*01:02:01:04 by one nucleotide substitution in codon 160 in exon 3.
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http://dx.doi.org/10.1111/tan.13961DOI Listing
September 2020

Characterization of the novel HLA-DQA1*05:05:05 allele by sequencing-based typing.

HLA 2020 Sep 23;96(3):372-373. Epub 2020 Jun 23.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Place Amélie Raba Léon, Bordeaux, France.

HLA-DQA1*05:05:05 differs from HLA-DQA1*05:05:01:07 by one nucleotide substitution in codon 111 in exon 3.
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http://dx.doi.org/10.1111/tan.13957DOI Listing
September 2020

Characterization of the novel HLA-DQA1*03:01:06 allele by sequencing-based typing.

HLA 2020 08 13;96(2):234-235. Epub 2020 Jun 13.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Place Amélie Raba Léon, Bordeaux, France.

HLA-DQA1*03:01:06 differs from HLA-DQA1*03:01:01:01 by one nucleotide substitution in codon 9 in exon 2.
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http://dx.doi.org/10.1111/tan.13952DOI Listing
August 2020

Characterization of the novel HLA-DQA1*01:49 allele by sequencing-based typing.

HLA 2020 08 13;96(2):233-234. Epub 2020 Jun 13.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Place Amélie Raba Léon, Bordeaux, France.

HLA-DQA1*01:49 differs from HLA-DQA1*01:01:01:06 by one nucleotide substitution in codon 9 in exon 2.
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http://dx.doi.org/10.1111/tan.13949DOI Listing
August 2020

Characterization of the novel HLA-DRB3*02:02:25 allele by sequencing-based typing.

HLA 2020 Sep 17;96(3):359-360. Epub 2020 Jun 17.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Place Amélie Raba Léon, Bordeaux, France.

HLA-DRB3*02:02:25 differs from HLA-DRB3*02:02:01:02 by one nucleotide substitution in codon 116 in exon 3.
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http://dx.doi.org/10.1111/tan.13945DOI Listing
September 2020

Characterization of the novel HLA-DQA1*03:15 allele by sequencing-based typing.

HLA 2020 08 12;96(2):236-237. Epub 2020 Jun 12.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Place Amélie Raba Léon, Bordeaux, France.

HLA-DQA1*03:15 differs from HLA-DQA1*03:01:01:01 by one nucleotide substitution in codon 79 in exon 2.
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http://dx.doi.org/10.1111/tan.13950DOI Listing
August 2020

A new HLA-DQA1 allele, HLA-DQA1*01:26.

HLA 2020 07 16;96(1):119-120. Epub 2020 Mar 16.

Laboratorio d'Immunogenetica dei Trapianti, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.

The novel allele HLA-DQA1*01:26 differs from HLA-DQA1*01:01:01:01 by one nucleotide substitution in exon 2.
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http://dx.doi.org/10.1111/tan.13858DOI Listing
July 2020

Matched-Pair Analysis of Transplant from Haploidentical, Unmanipulated Bone Marrow Donor versus HLA Identical Sibling for Patients with Hematologic Malignancies.

Biol Blood Marrow Transplant 2020 06 14;26(6):1113-1118. Epub 2020 Feb 14.

Hematology, Stem Cell Transplant Unit, University Tor Vergata, Rome, Italy. Electronic address:

A matched-pair analysis of transplant-related outcomes was carried out in 116 of 255 consecutive patients who received transplants from an HLA identical sibling (n = 58) or haploidentical related donor (n = 58). The 2 patient series were matched with 9 variables: period of transplant, patient and donor age, sex, diagnosis, disease phase, conditioning regimen, donor-recipient sex, and cytomegalovirus (CMV) status combinations. As graft-versus-host disease (GVHD) prophylaxis, all patients received the standard cyclosporine and methotrexate association with the addition of anti-thymocyte globulins, mycophenolate mofetil, and basiliximab in haploidentical, unmanipulated bone marrow recipients. Anti-infectious management, transfusion policy, and supportive care were identical for all patients. By comparing the 2 patient series, no statistically significant difference was observed for the cumulative incidence of advanced acute and extensive chronic GVHD, transplant-related mortality, and relapse. With a median follow-up of 3.5 years, the 5-year disease-free survival was 37% ± 6% and 36% ± 6% for HLA identical sibling and haploidentical recipients, respectively. The results of transplant from HLA identical siblings and haploidentical donors are comparable. Regardless of the HLA matching, other factors known to affect the transplant outcomes, such as donor-recipient age, sex, and CMV status combinations, might drive the search for the best donor.
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http://dx.doi.org/10.1016/j.bbmt.2020.02.005DOI Listing
June 2020

Characterization of the novel HLA-DPA1*01:03:19 allele by sequencing-based typing.

HLA 2020 07 12;96(1):129-130. Epub 2020 Feb 12.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Bordeaux, France.

HLA-DPA1*01:03:19 differs from DPA1*01:03:01:02 by one nucleotide substitution in codon 190 in exon 4.
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http://dx.doi.org/10.1111/tan.13830DOI Listing
July 2020

Characterization of the novel HLA-DRB3*02:142 allele by sequencing-based typing.

HLA 2020 06 10;95(6):581-582. Epub 2020 Feb 10.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Bordeaux, France.

HLA-DRB3*02:142 differs from HLA-DRB3*02:02:01:02 by one nucleotide substitution in codon 98 in exon 3.
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http://dx.doi.org/10.1111/tan.13819DOI Listing
June 2020

Characterization of the novel HLA-DQA1*05:23 allele by sequencing-based typing.

HLA 2020 07 28;96(1):120-121. Epub 2020 Feb 28.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Bordeaux, France.

HLA-DQA1*05:23 differs from HLA-DQA1*05:01:01:02 by one nucleotide substitution in codon 58 in exon 2.
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http://dx.doi.org/10.1111/tan.13826DOI Listing
July 2020

Characterization of the novel HLA-DQA1*04:08 allele by sequencing-based typing.

HLA 2020 06 28;95(6):584-585. Epub 2020 Feb 28.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Bordeaux, France.

HLA-DQA1*04:08 differs from HLA-DQA1*04:01:01:01 by one nucleotide substitution in codon 217 in exon 4.
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http://dx.doi.org/10.1111/tan.13820DOI Listing
June 2020

Effect of p53 activation through targeting MDM2/MDM4 heterodimer on T regulatory and effector cells in the peripheral blood of Type 1 diabetes patients.

PLoS One 2020 29;15(1):e0228296. Epub 2020 Jan 29.

Infectivology and Clinical Trials Research Department, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Various immunotherapies for the treatment of type 1 diabetes are currently under investigation. Some of these aim to rescue the remaining beta cells from autoimmune attack caused by the disease. Among the strategies employed, p53 has been envisaged as a possible target for immunomodulation. We studied the possible effect of p53 activation on Treg subsets and Treg/Teff balance in type 1 diabetes patients' PBMC. Upon p53 activation, we observed an increase in CD8+ Treg and activated CD8+ Teff whilst CD8+ Teff cells significantly decreased in healthy PBMC when stimulated with anti-CD3/CD28. No effect was detected on percentages of CD4+ Treg, while a reduction was seen in CD4+ Teff cells and an increase in activated CD4+ Teff cells. In patients' PBMC, upon p53 activation followed by 6 days of anti-CD3/CD28 stimulation, CD8+ Treg and activated CD8+ Teff were increased while CD8+ Teff were decreased. No differences were detected in the CD4+ counterparts. CD8+ Teff PD1+, CD8+ Teff PD1low were increased upon p53 activation in type 1 diabetics compared to controls while CD8+ Teff PD1high were increased in both groups. The same increased percentages were detected for CD4+ counterparts. CD4+ Treg PD1high cells were decreased in diabetics upon p53 activation at day 6 of anti-CD3/CD28 stimulation. In conclusion, a Teff dysregulation is observed upon p53 activation suggesting that molecules promoting p53 cannot be used for therapy in type 1 diabetics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228296PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988923PMC
April 2020

Characterization of the novel HLA-DRB3*03:37 allele by sequencing-based typing.

HLA 2020 02 21;95(2):152-153. Epub 2019 Nov 21.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Bordeaux, France.

HLA-DRB3*03:37 differs from HLA-DRB3*03:01:01:01 by one nucleotide substitution in codon 205 in exon 4.
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http://dx.doi.org/10.1111/tan.13750DOI Listing
February 2020

Characterization of the novel HLA-DPA1*01:03:16 allele by sequencing-based typing.

HLA 2020 02 20;95(2):158-159. Epub 2019 Nov 20.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Bordeaux, France.

HLA-DPA1*01:03:16 differs from HLA-DPA1*01:03:01:03 by one nucleotide substitution in codon 171 in exon 3.
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http://dx.doi.org/10.1111/tan.13745DOI Listing
February 2020

Characterization of the novel HLA-DRB3*02:02:23 allele by sequencing-based typing.

HLA 2020 02 14;95(2):150-151. Epub 2019 Nov 14.

Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.

HLA-DRB3*02:02:23 differs from HLA-DRB3*02:02:01:02 by one nucleotide substitution in codon 218 in exon 4.
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http://dx.doi.org/10.1111/tan.13748DOI Listing
February 2020

Characterization of the novel HLA-DPA1*02:26 allele by sequencing-based typing.

HLA 2020 02 20;95(2):160-161. Epub 2019 Nov 20.

Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.

HLA-DPA1*02:26 differs from HLA-DPA1*02:01:01:02 by one nucleotide substitution in codon 186 in exon 4.
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http://dx.doi.org/10.1111/tan.13744DOI Listing
February 2020

Human leucocyte antigen diversity: A biological gift to escape infections, no longer a barrier for haploidentical Hemopoietic Stem Cell Transplantation.

Int J Immunogenet 2020 Feb 27;47(1):34-40. Epub 2019 Oct 27.

Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy.

Since the beginning of life, every multicellular organism appeared to have a complex innate immune system although the adaptive immune system, centred on lymphocytes bearing antigen receptors generated by somatic recombination, arose in jawed fish approximately 500 million years ago. The major histocompatibility complex MHC, named the Human leucocyte antigen (HLA) system in humans, represents a vital function structure in the organism by presenting pathogen-derived peptides to T cells as the main initial step of the adaptive immune response. The huge level of polymorphism observed in HLA genes definitely reflects selection, favouring heterozygosity at the individual or population level, in a pathogen-rich environment, although many are located in introns or in exons that do not code for the antigen-biding site of the HLA. Over the past three decades, the extent of allelic diversity at HLA loci has been well characterized using high-resolution HLA-DNA typing and the number of new HLA alleles, produced through next-generation sequencing methods, is even more rapidly increasing. The level of the HLA system polymorphism represents an obstacle to the search of potential compatible donors for patients affected by haematological disease proposed for a hematopoietic stem cell transplant (HSCT). Data reported in literature clearly show that antigenic and/or allelic mismatches between related or unrelated donors and patients influences the successful HSCT outcome. However, the recent development of the new transplant strategy based on the choice of haploidentical donors for HSCT is questioning the role of HLA compatibility, since the great HLA disparities present do not worsen the overall clinical outcome. Nowadays, NGS has contributed to define at allelic levels the HLA polymorphism and solve potential ambiguities. However, HLA functions and tissue typing probably need to be further investigated in the next future, to understand the reasons why in haploidentical transplants the presence of a whole mismatch haplotype between donors and recipients, both the survival rate and the incidence of acute GvHD or graft rejection are similar to those reported for unrelated HSCTs.
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http://dx.doi.org/10.1111/iji.12459DOI Listing
February 2020

Evaluation of the AllType kit for HLA typing using the Ion Torrent S5 XL platform.

HLA 2020 01 23;95(1):30-39. Epub 2019 Oct 23.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Bordeaux, France.

HLA genotyping by next-generation sequencing is now widely performed. We aimed at evaluating the performance of the One Lambda AllType kit using Thermo Fisher Scientific reagents on the Ion S5 XL platform. Reads were analyzed using the TypeStream Visual software. We performed 15 runs between April and September 2018 to type DNA at the HLA-A/B/C/DRB1/3/4/5/DQA1/DQB1/DPA1/DPB1 loci from 340 samples and 15 positive controls. We observed only seven (0.1%) critical mistakes among the 6009 alleles typed, corresponding to two allele dropouts, one false heterozygous typing assignment, and four phasing abnormalities. Among the 1793 presumably new alleles detected by the analysis software, 11 displayed exon mismatches, of which nine were confirmed as new alleles and two had been described previously. Intron mismatches were observed among the remaining presumably new alleles, of which 371 were considered as probably new, and 1411 were rejected for at least one sequence feature such as homopolymers (n = 1206), nucleotide doublet repeats (n = 26), low read depth (<200 reads, n = 93), high background (>20%, n = 79), or phasing abnormalities (n = 7). A comparison of the AllType results with those obtained using other methods at the second-field resolution level showed 99.5% (1497/1504) concordance for the HLA-A/B/C/DRB1/DQB1/DPB1 loci. Similar agreement was observed between the HLA-C or HLA-DRB3/4/5 results and common linkage disequilibrium, with 96.6% (657/680) and 97.2% (530/545) concordance, respectively. Therefore, the AllType kit used with the Ion S5 XL platform displayed satisfactory performance for HLA typing in current clinical practice.
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http://dx.doi.org/10.1111/tan.13708DOI Listing
January 2020

Characterization of the novel HLA-DRB3*02:96 allele by sequencing-based typing.

HLA 2019 11 16;94(5):464-465. Epub 2019 Aug 16.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Bordeaux, France.

HLA-DRB3*02:96 differs from HLA-DRB3*02:02:01:01 by one nucleotide substitution in codon 189 in exon 4.
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http://dx.doi.org/10.1111/tan.13653DOI Listing
November 2019

Characterization of the novel HLA-DQA1*01:27 allele by sequencing-based typing.

HLA 2019 10 12;94(4):392-393. Epub 2019 Aug 12.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Bordeaux, France.

HLA-DQA1*01:27 differs from HLA-DQA1*01:01:01:01 by one nucleotide substitution in codon 221 in exon 4.
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http://dx.doi.org/10.1111/tan.13647DOI Listing
October 2019

Characterization of the novel HLA-DPA1*01:20 allele by sequencing-based typing.

HLA 2019 10 12;94(4):396-397. Epub 2019 Aug 12.

CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Bordeaux, France.

HLA-DPA1*01:20 differs from HLA-DPA1*01:03:01:01 by one nucleotide substitution in codon 5 in exon 2.
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http://dx.doi.org/10.1111/tan.13648DOI Listing
October 2019