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Many specificities single out HLA‐F: its structure, expression regulation at cell membrane and function. HLA‐F mRNA is detected in the most cell types and the protein is localized in the ER and Golgi apparatus. When expressed at cell surface, HLA‐F may be associated to β2‐microglobulin and peptide or expressed as an open‐conformer molecule. HLA‐F reaches the membrane upon activation of different primary cell types and cell‐lines. HLA‐F has its highest affinity for the KIR3DS1‐activating NK receptor, but also binds inhibitory immune receptors. Some studies reported that HLA‐F expression is associated with its genotype. Higher HLA‐F mRNA expression associated with F*01:01:02, and 3 noncoding SNPs, rs1362126, rs2523405, and rs2523393, located in HLA‐F‐AS1 or upstream the HLA‐F sequence were associated with HLA‐F mRNA expression. Given the implication of HLA‐F in many clinical setting, and the undisclosed process of its expression regulation, we aim to confirm the effect of the aforementioned SNPs with HLA‐F transcriptional and protein expression. We analyzed the distribution, frequency and linkage disequilibrium of these SNPs at worldwide scale in the 1000 Genomes Project samples. Influence on the genotype of each SNP on HLA‐F expression was explored using RNAseq data from the 1000 Genomes Project, and using Q‐PCR and intracellular cytometry in PBMC from healthy individuals. Our results show that the SNPs under studied displayed remarkably different allelic proportion according to geography and confirm that rs1362126, rs2523405, and rs2523393 displayed the most concordant results, with the highest effect size and a double‐dose effect. [ABSTRACT FROM AUTHOR]

Uncontrolled inflammation of the airways in chronic obstructive lung diseases leads to exacerbation, accelerated lung dysfunction and respiratory insufficiency. Among these diseases, asthma affects 358 million people worldwide. Human bronchial epithelium cells (HBEC) express both anti‐inflammatory and activating molecules, and their deregulated expression contribute to immune cell recruitment and activation, especially platelets (PLT) particularly involved in lung tissue inflammation in asthma context. Previous results supported that HLA‐G dysregulation in lung tissue is associated with immune cell activation. We investigated here HLA‐F expression, reported to be mobilised on immune cell surface upon activation and displaying its highest affinity for the KIR3DS1‐activating NK receptor. We explored HLA‐F transcriptional expression in HBEC; HLA‐F total expression in PBMC and HBEC collected from healthy individuals at rest and upon chemical activation and HLA‐F membrane expression in PBMC, HBEC and PLT collected from healthy individuals at rest and upon chemical activation. We compared HLA‐F transcriptional expression in HBEC from healthy individuals and asthmatic patients and its surface expression in HBEC and PLT from healthy individuals and asthmatic patients. Our results support that HLA‐F is expressed by HBEC and PLT under healthy physiological conditions and is retained in cytoplasm, barely expressed on the surface, as previously reported in immune cells. In both cell types, HLA‐F reaches the surface in the inflammatory asthma context whereas no effect is observed at the transcriptional level. Our study suggests that HLA‐F surface expression is a ubiquitous post‐transcriptional process in activated cells. It may be of therapeutic interest in controlling lung inflammation. [ABSTRACT FROM AUTHOR]

We describe the novel KIR3DL1*182 allele and confirmed the 3DL1*15002 allele. [ABSTRACT FROM AUTHOR]

We describe nine novel HLA‐J alleles validated by in silico and experimental data. [ABSTRACT FROM AUTHOR]

We isolated 11 novel HLA alleles in the 1000 Genomes Project using PolyPheMe software. [ABSTRACT FROM AUTHOR]

We describe the full gene sequences of 15 HLA‐H alleles. [ABSTRACT FROM AUTHOR]

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E(⁎)01:01 and HLA-E(⁎)01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p = 0.01). In multivariate analysis, HLA-E(⁎)01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E(⁎)01:01 status (HR: 3.563 (CI 95%, 1.016-12), p = 0.047). HLA-E allele did not affect pathogen infection or the production of de novo DSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort. [ABSTRACT FROM AUTHOR]

To lower the alloimmunization risk following transfusion in blacks, we developed two genotyping assays for large-scale screening of Comorian and Afro-Caribbean donors. One was a multiplex SNaPshot assay designed to identify ce (340), ceMO/AR/EK/BI/SM, ce , ce (1006) and KEL*6/*7 alleles. The other was a multiplex fragment assay designed to detect RHD, RHDψ and RHCE*C and 455A>C transversion consistent with (C)ce Type 1 and DIII Type5 ce. Variant RHCE*ce alleles or RH haplotypes were detected in 58·69% of Comorians and 41·23% of Afro-Caribbeans. The ce allele, (C)ce Type 1, and DIII Type 5 ce haplotypes were identified respectively in 39·13%, 14·67% and 4·88% of Comorians and 32·23%, 5·28% and 1·76% of Afro-Caribbeans. Genotypes consistent with partial D, C, c and/or e antigen expression were observed in 26·08% of Comorians and 14·69% of Afro-Caribbeans. No homozygous genotype corresponding to the RH:-18, -34, and -46 phenotypes were found. However, over 50% of genotypes produced low-prevalence antigens at risk for negative recipients, i.e., V, VS, JAL, and/or KEL6. One new variant RHCE*ce (712) allele was identified. This is the first determination of variant RHCE and KEL allele frequencies. Results indicate the most suitable targets for molecular assay screening to optimize use of compatible blood units and lower immunization risk. [ABSTRACT FROM AUTHOR]

Molecular RHD blood group typing is very efficient for managing donors and patients carrying any of the various molecular types of weak D and DEL. The purpose of the work was to develop a multiplex polymerase chain reaction (PCR) SNaPshot assay for simultaneous detection of weak D and DEL alleles that are prevalent in Europeans, Africans, and Asians. Preliminary profiling was carried out on single-nucleotide polymorphisms (SNPs) associated with 13 prevalent RHD alleles, that is, weak D Types 1, 2, 3, 4.0, 4.0.1, 4.1, 4.2, 5, 11, 15, and 17; RHD(IVS3+ 1g> a); and RHD(K409K). Multiplex PCR was used to amplify six RHD regions encompassing 14 SNPs. Identification was obtained by incorporation of the complementary dye single base at the 3′-end of each probe-primer. A prospective analysis was then carried out on 152 blood samples from patients (n = 53) and donors (n = 88) with equivocal RhD serology and pregnant women (n = 11). After validation, our SNaPshot assay allowed direct genotyping of 82.9% of samples overall and 100% of samples harboring weak D Types 1, 2, 3, and 4.1 alleles. In the remaining 17.1% of samples overall, sequence investigation allowed accurate genotyping. In addition, four novel RHD alleles were identified, that is, RHD(S256P), RHD(L390L), RHD(F410V), and RHD(IVS4-2a> g). The SNaPshot assay described herein is a helpful supplementary tool for resolving doubtful RhD serology. By allowing accurate identification of weak D and DEL alleles this assay should allow better management of the donors and the patients genotyped weak D Types 1, 2, 3, and 4.1 who can receive D+ blood units. [ABSTRACT FROM AUTHOR]

We describe nine novel HLA‐F alleles. [ABSTRACT FROM AUTHOR]