Next-generation sequencing HLA

Conventional treatments have shown a limited efficacy for pancreatic cancer, and immunotherapy is an emerging option for treatment of this highly fatal malignancy. Neoantigen is critical to improving the efficacy of tumor-specific immunotherapy. The cancer and peripheral blood specimens from human leukocyte antigen (HLA)-A0201 positive pancreatic cancer patient were subjected to next-generation sequencing and bioinformatics analyses were performed to screen high-affinity and highly stable neoepitopes. The activation of cytotoxic T lymphocytes (CTLs) by the mutBCL2A111-20 neoepitope targeting B-cell lymphoma 2-related protein A1 (BCL2A1) mutant epitope was investigated, and the cytotoxicity of mutBCL2A111-20 neoepitope-specific CTLs to pancreatic cancer cells was evaluated...

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease that affects individuals of diverse racial and ethnic backgrounds. There is currently no cure for ALS, and the number of efficient disease-modifying drugs for ALS is limited to a few, despite the large number of clinical trials conducted in recent years. The latter could be attributed to the significant heterogeneity of ALS clinical phenotypes even in their familial forms. To address this issue, we conducted postmortem genetic screening of two female patients with sporadic ALS (sALS) and contrasting clinical phenotypes...

The HLA-B*40:538 allele differs from HLA-B*40:01:02:01 at position 905 C→T in exon 5.

Low copy numbers (CNs) of C4 genes are associated with systemic autoimmune disorders and affects autoantibody diversity and disease subgroups. The primary objective of this study was to characterize diversity of complement (C4) and C4-Human Endogenous Retrovirus (HERV) gene copy numbers in SLE. We also sought to assess the association of C4 and C4-HERV CNs with serum complement levels, autoantibodies, disease phenotypes and activity. Finally, we checked the association of C4 and HERV CNs with specific HLA alleles...

Assessing donor/recipient HLA compatibility at the eplet level requires second field DNA typings but these are not always available. These can be estimated from lower-resolution data either manually or with computational tools currently relying, at best, on data containing typing ambiguities. We gathered NGS typing data from 61,393 individuals in 17 French laboratories, for loci A, B, and C (100% of typings), DRB1 and DQB1 (95.5%), DQA1 (39.6%), DRB3/4/5, DPB1, and DPA1 (10.5%). We developed HaploSFHI, a modified iterative maximum likelihood algorithm, to impute second field HLA typings from low- or intermediate-resolution ones...

Behçet's disease (BD) manifests as an autoimmune disorder featuring recurrent ulcers and multi-organ involvement, influenced by genetic factors associated with both HLA and non-HLA genes, including TNF-α and ERAP1. The study investigated the susceptible alleles of both Class I and II molecules of the HLA gene in 56 Thai BD patients and 192 healthy controls through next-generation sequencing using a PacBio kit. The study assessed 56 BD patients, primarily females (58.9%), revealing diverse manifestations including ocular (41...

Identification of the novel HLA-A*02:1148 and HLA-B*44:386 alleles by next-generation sequencing.

The novel HLA-B*13:191 allele was detected during the HLA typing for kidney transplantation.

Nucleotide substitutions in the 5'UTR and exon 2 of HLA-B*35:01:01:05 result in a novel allele, HLA-B*35:01:77.

We identified two novel HLA-DQB1 alleles by NGS, HLA-DQB1*03:519 and HLA-DQB1*06:01:35.

The novel HLA-DPA1*02:02:15 allele differs from HLA-DPA1*02:02:02:01 by one nucleotide substitution in exon 1.

HLA-C*03:94:02 differs from HLA-C*03:94:01 by a single nucleotide substitution in exon 2 (codon 17 GGA->GGG).

The new HLA-DPA1*01:182 allele differs from HLA-DPA1*01:03:01:04 by a single mismatch in exon 4.

A novel HLA-C*07 allele, now officially designated HLA-C*07:02:150, was identified by next-generation sequencing.

HLA-C*07:04:29 differs from HLA-C*07:04:01:01 by a single substitution in exon 4.

Pustular skin diseases, with pustular psoriasis (PP) being the prototype, are immune-mediated diseases characterized by the presence of multiple pustules, resulting from neutrophil accumulation in the layer of epidermis. Sterile skin pustular eruption, like PP, is also observed in 20-30% of patients with adult-onset immunodeficiency syndrome (AOID) and anti-interferon γ autoantibodies (IFN-γ), leading to challenges in classification and diagnosis. While the mechanism underlying this similar phenotype remains unknown, genetic factors in relation to the immune system are suspected of playing an important role...

Rheumatoid arthritis (RA) has an estimated heritability of nearly 50%, which is particularly high in seropositive RA. HLA alleles account for a large proportion of this heritability, in addition to many common single-nucleotide polymorphisms with smaller individual effects. Low-frequency and rare variants, such as those captured by next-generation sequencing, can also have a large role in heritability in some individuals. Rare variant discovery has informed the development of drugs such as inhibitors of PCSK9 and Janus kinases...

Relapsed and refractory diffuse large B-cell lymphoma (DLBCL) is associated with poor prognosis. As such, a comprehensive analysis of intratumoral components, intratumoral heterogeneity, and the immune microenvironment is essential to elucidate the mechanisms driving the progression of DLBCL and to develop new therapeutics. Here, we used single-cell transcriptome sequencing and conventional bulk next-generation sequencing (NGS) to understand the composite tumor landscape of a single patient who had experienced multiple tumor recurrences following several chemotherapy treatments...

HLA-C*01:02:01:70 differs from the HLA-C*01:02:01:01 allele by one nucleotide substitution in the intron 4.

The novel HLA-C*14:159 allele was detected during the routine HLA typing for kidney transplantation.