Identification of the novel HLA-DPA1*01:130 allele by next-generation sequencing.

The novel HLA-DPA1*01:130 allele differs from HLA-DPA1*01:03:01:03 by one nucleotide substitution in Exon 3.

The new HLA-DQB1*05:304 allele identified in an Italian patient.

DQB1*05:304 allele was identical to DQB1*05:02:01 except for a single nucleotide substitution.

Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia.

We developed an innovative and efficient, feeder-free culture method to genetically modify and expand peripheral blood-derived NK cells with high proliferative capacity, while preserving the responsiveness of their native activating receptors. Activated peripheral blood NK cells were efficiently transduced by a retroviral vector, carrying a second-generation CAR targeting CD19. CAR expression was demonstrated across the different NK-cell subsets. CAR.CD19-NK cells display higher antileukemic activity toward CD19+ cell lines and primary blasts obtained from patients with B-cell precursor ALL compared with unmodified NK cells. In vivo animal model data showed that the antileukemia activity of CAR.CD19-NK cell is superimposable to that of CAR-T cells, with a lower xenograft toxicity profile. These data support the feasibility of generating feeder-free expanded, genetically modified peripheral blood NK cells for effective "off-the-shelf" immuno-gene-therapy, while their innate alloreactivity can be safely harnessed to potentiate allogeneic cell therapy.

A new allele, HLA-DQA1*02:01:02.

The new allele, HLA-DQA1*02:01:02 differs from DQA1*02:01:01:01 by C to T substitution in exon 2.

Identification of the novel allele, HLA-A*02:653, in an Italian patient.

HLA-A*02:653 differs from A*02:01:01:01 by a C to T substitution in exon 2.

A new allele, HLA-A*03:275N.

The novel allele HLA-A*03:275N differs from HLA-A*03:01:01:01 by 1 nucleotide substitutions in exon 2.

Identification of the new HLA-DQA1*01:15N allele in an Italian patient.

The novel allele DQA1*01:15N differs from DQA1*01:03:01:01 by 1 nucleotide substitutions in exon 2.

Identification of the new C*07:555 allele in an unrelated donor for HSCT.

HLA-C*07:555 differs from C*07:01:01:01 by a C to G substitution in exon 2.

Common and well-documented HLA alleles over all of Europe and within European sub-regions: A catalogue from the European Federation for Immunogenetics.

BACKGROUND: A catalogue of common and well-documented (CWD) human leukocyte antigen (HLA), previously established by the American Society for Histocompatibility and Immunogenetics (ASHI), is widely used as indicator for typing ambiguities to be resolved in tissue transplantation or for checking the universality of any HLA allele in the world. However, European population samples, which are characterized by a substantial level of genetic variation, are underrepresented in the ASHI catalogue. Therefore, the Population Genetics Working Group of the European Federation for Immunogenetics (EFI) has facilitated data collection for an European CWD catalogue. MATERIALS AND METHODS: To this end, 2nd-field HLA-A, -B, -C,- DRB1,- DQA1,- DQB1 and -DPB1 data of 77 to 121 European population samples (21 571-3 966 984 individuals) from 3 large databases, HLA-net/Gene[VA], allelefrequencies.net and DKMS, were analysed. RESULTS: The total number of CWD alleles is similar in the EFI (N = 1048) and ASHI (N = 1031) catalogues, but the former counts less common (N = 236 vs 377) and more well-documented (N = 812 vs 654) alleles than the latter, possibly reflecting differences in sample numbers and sizes. Interestingly, approximately half of the CWD alleles reported by EFI were not reported by ASHI and vice-versa, underlining the distinct features of the two catalogues. Also, although 78 common alleles are widely distributed across Europe, some alleles are only common within specific sub-regions, showing regional variability. CONCLUSION: Although the definition of CWD alleles itself is affected by different parameters, calling for current updates of the list, the EFI CWD catalogue provides new insights into European population genetics and will be a very useful tool for tissue-typing laboratories in and beyond Europe.

Characterization of the novel HLA-C*02:106 allele in a hematopoietic stem cell volunteer donor.

HLA-C*02:106 allele differs from C*02:02:02:01 by a C to T substitution in exon 4.

HLA-C*18:01: A Rare Allele in the European Caucasian Population Coinciding with Difficult-to-Treat Plaque Psoriasis.

BACKGROUND: Advances in knowledge about the metabolic pathways involved in the pathogenesis of psoriasis and related diseases have led to a search for new therapeutic targets and the development of new biological drugs. Several studies have focused on HLA-C*06 and investigated correlations between the genetic risk factors of psoriasis and clinical parameters such as the severity of the disease and the response to treatment. OBJECTIVE: Our objective is to share experience from our institution in the observation of two patients with severe chronic plaque psoriasis who were unresponsive to any anti-TNF-α treatment and only partially responsive to ustekinumab. The patients are carriers of a rare allele of HLA-C that occurs in Caucasians. METHODS: The patients with moderate-to-severe chronic plaque psoriasis, and candidates for biological therapy were typed for the HLA-C locus at high resolution via polymerase chain reaction sequence-specific oligonucleotide probes (PCR-SSOP) using a commercial kit (LAB(®)Type, One Lambda Inc., Canoga Park, CA, USA). The socio-demographic variables and clinical data were collected. RESULTS: In our cohort of 134 patients, only two showed the presence of the allele HLA-C*18:01. To our knowledge, a coincidence between HLA-C*18 and severe psoriasis in Caucasian patients has not previously been described. The fact that both of these patients showed the same clinical history (unresponsive to any anti-TNF-α treatment and partially responsive to ustekinumab) cannot be attributed to a random observation because HLA-C*18 is extremely rare in Europe. As a consequence, at this latitude, it probably indicates a severe disease for which the proper therapy has still not been identified.

A nucleotide insertion in Exon 2 is responsible for a new HLA-DRB1 null allele, HLA-DRB1*14:166N.

DRB1*14 is identical to DRB1*14:54:01 except for a single nucleotide insertion of A in position 175 in Exon 2.

HLA-A-B-C-DRB1-DQB1 phased haplotypes in 124 Nigerian families indicate extreme HLA diversity and low linkage disequilibrium in Central-West Africa.

The simultaneous typing of five-HLA loci at high resolution and the availability of pedigree data allowed us to characterize extended five-locus phased haplotypes in 124 Nigerian families and to compare the observed frequencies with those expected by an expectation-maximization algorithm for unphased data. Despite the occurrence of some frequent alleles at each locus (e.g. B*53:01, which is assumed to protect against Plasmodium falciparum), as many as 82% of the sampled individuals carry two unique five-locus haplotypes and only three extended haplotypes with frequency above 1% exhibit significant linkage disequilibrium. Although preliminary, these results reveal an extreme level of HLA diversity in the Nigerian population, which reflects both its multi-ethnic composition and the very ancient demographic history of African populations.

Sequence-based typing characterization of the novel HLA-DRB3*01:16 allele, identified in an Italian family.

The novel DRB1*01:16 allele differs for G to T substitution at position 595 from DRB3*01:01P.

HLA-C*07:02:60, a variant of HLA-C*07 found in an unrelated volunteer stem cell donor.

The allele HLA-C*07:02:60 differs from HLA-C*07:02:01:01 by a silent nucleotide substitution in exon 4.

Hematopoietic SCT for the Black African and non-Black African variants of sickle cell anemia.

Sickle cell anemia (SCA) remains associated with high risks of morbidity and early death. Allogeneic hematopoietic SCT (HSCT) is the only curative treatment for SCA. We report our experience with transplantation in a group of patients with the non-Black African variant and the Black African variant of SCA. This study included 40 consecutive SCA patients (13 patients with the non-Black African variant and 27 with the Black African variant) who underwent BM transplantation from HLA-identical sibling donors between June 2004 and May 2013, following a myeloablative-conditioning regimen. All patients obtained sustained engraftment. One patient (non-Black African variant) became a stable mixed chimera with 25% donor cells more than 6 years after transplantation. The probabilities of survival, SCA-free survival and TRM at 5 years after transplant were 91%, 91% and 9%, respectively. All surviving patients remained free of any SCA-related events after transplantation. Our results confirm that it is possible to offer a greater than 90% chance of cure to children with SCA. HSCT should be considered the standard of care for who have an HLA-identical donor, before complications result from the sickling of RBC.

Influence of the HLA characteristics of Italian patients on donor search outcome in unrelated hematopoietic stem cell transplantation.

The information regarding the probability of finding a matched unrelated donor (MUD) within a relatively short time is crucial for the success of hematopoietic stem cell transplantation (HSCT), particularly in patients with malignancies. In this study, we retrospectively analyzed 315 Italian patients who started a search for a MUD, in order to assess the distribution of human leukocyte antigen (HLA) alleles and haplotypes in this population of patients and to evaluate the probability of finding a donor. Comparing two groups of patients based on whether or not a 10/10 HLA-matched donor was available, we found that patients who had a fully-matched MUD possessed at least one frequent haplotype more often than the others (45.6% vs 14.3%; P = 0.000003). In addition, analysis of data pertaining to the HLA class I alleles distribution showed that, in the first group of patients, less common alleles were under-represented (20.2% vs 40.0%; P = 0.006). Therefore, the presence of less frequent alleles represents a negative factor for the search for a potential compatible donor being successful, whereas the presence of one frequent haplotype represents a positive predictive factor. Antigenic differences between patient and donor observed at C and DQB1 loci, were mostly represented by particular B/C or DRB1/DQB1 allelic associations. Thus, having a particular B or DRB1 allele, linked to multiple C or DQB1 alleles, respectively, might be considered to be associated with a lower probability of a successful search. Taken together, these data may help determine in advance the probability of finding a suitable unrelated donor for an Italian patient.