Identification of the novel HLA-DPA1*02:07:04 allele by next-generation sequencing.

The novel HLA-DPA1*02:07:04 allele was detected during the HLA typing for kidney transplantation.

The novel HLA-DPA1*01:182 allele identified in a Brazilian bone marrow donor.

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

The novel HLA-DPA1*02:117 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DPA1*02:117 differs from HLA-DPA1*02:02:02:01 by one nucleotide in exon 2.

Identification of the novel HLA-DPA1*02:02:15 allele by next-generation sequencing.

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

The novel HLA-DPA1*02:86 allele was identified by next-generation sequencing.

HLA-DPA1*02:86 differs from HLA-DPA1*02:01:01 by a single nucleotide substitution at position 680 C > A in exon 4.

Characterization of the novel HLA-DPA1*02:124 allele in a Korean individual by next-generation sequencing.

HLA-DPA1*02:124 differs from HLA-DRB1*02:02:02:01 by one nucleotide substitution in codon 5 in exon 2.

HLA-DPA1*02:01:25, a novel allele with a synonymous transition in exon 2 identified by next-generation sequencing.

HLA-DPA1*02:01:25 differs from DPA1*02:01:01:02 by a synonymous transition in exon 2.

Characterization of seven novel HLA-DPA1*01:03:01 non-coding variants by next-generation sequencing.

Seven different single nucleotide substitutions in non-coding regions gave rise to novel HLA-DPA1*01:03:01 variants.

Characterization of the novel HLA-DPA1*02:122 allele by sequencing-based typing.

HLA-DPA1*02:122 differs from HLA-DPA1*02:01:01:02 by one nucleotide substitution in codon 78 in exon 2.

Characterization of the novel HLA-DPA1*01:03:51 allele by sequencing-based typing.

HLA-DPA1*01:03:51 differs from HLA-DPA1*01:03:01:01 by one nucleotide substitution in codon 146 in exon 3.

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.

HLA-DPA1*02:01~B1*01:01 is a risk haplotype for primary sclerosing cholangitis mediating activation of NKp44+ NK cells.

OBJECTIVE: Primary sclerosing cholangitis (PSC) is characterised by bile duct strictures and progressive liver disease, eventually requiring liver transplantation. Although the pathogenesis of PSC remains incompletely understood, strong associations with HLA-class II haplotypes have been described. As specific HLA-DP molecules can bind the activating NK-cell receptor NKp44, we investigated the role of HLA-DP/NKp44-interactions in PSC. DESIGN: Liver tissue, intrahepatic and peripheral blood lymphocytes of individuals with PSC and control individuals were characterised using flow cytometry, immunohistochemical and immunofluorescence analyses. HLA-DPA1 and HLA-DPB1 imputation and association analyses were performed in 3408 individuals with PSC and 34 213 controls. NK cell activation on NKp44/HLA-DP interactions was assessed in vitro using plate-bound HLA-DP molecules and HLA-DPB wildtype versus knock-out human cholangiocyte organoids. RESULTS: NKp44+NK cells were enriched in livers, and intrahepatic bile ducts of individuals with PSC showed higher expression of HLA-DP. HLA-DP haplotype analysis revealed a highly elevated PSC risk for HLA-DPA1*02:01~B1*01:01 (OR 1.99, p=6.7×10-50). Primary NKp44+NK cells exhibited significantly higher degranulation in response to plate-bound HLA-DPA1*02:01-DPB1*01:01 compared with control HLA-DP molecules, which were inhibited by anti-NKp44-blocking. Human cholangiocyte organoids expressing HLA-DPA1*02:01-DPB1*01:01 after IFN-γ-exposure demonstrated significantly increased binding to NKp44-Fc constructs compared with unstimulated controls. Importantly, HLA-DPA1*02:01-DPB1*01:01-expressing organoids increased degranulation of NKp44+NK cells compared with HLA-DPB1-KO organoids. CONCLUSION: Our studies identify a novel PSC risk haplotype HLA-DP A1*02:01~DPB1*01:01 and provide clinical and functional data implicating NKp44+NK cells that recognise HLA-DPA1*02:01-DPB1*01:01 expressed on cholangiocytes in PSC pathogenesis.

Identification of the novel HLA-DPA1*01:149 allele by next-generation sequencing.

The novel HLA-DPA1*01:149 allele differs from HLA-DPA1*01:03:01:05 by one nucleotide substitution in exon 2.

Identification of the novel HLA-DPA1*02:110:02 allele by next-generation sequencing.

The novel HLA-DPA1*02:110:02 allele differs from HLA-DPA1*02:01:01:06 by one nucleotide substitution in exon 4.

Characterization of the novel HLA-DPA1*01:159 allele by sequencing-based typing.

HLA-DPA1*01:159 differs from HLA-DPA1*01:03:01:03 by one nucleotide substitution in codon 120 in exon 3.

Characterization of the novel HLA-DPA1*02:115 allele by sequencing-based typing.

HLA-DPA1*02:115 differs from HLA-DPA1*02:01:01:06 by one nucleotide substitution in codon 224 in exon 4.

Four novel HLA alleles: HLA-DPA1*01:03:01:68, -DPA1*01:03:01:71, -DQA1*02:01:01:06, and -DQB1*06:03:01:19.

Four novel HLA Class II alleles, HLA-DPA1*01:03:01:68, -DPA1*01:03:01:71, -DQA1*02:01:01:06, and -DQB1*06:03:01:19, characterized in Spanish individuals.

Discovery of three novel HLA-DPA1 alleles, HLA-DPA1*01:147N, 01:03:47, and 02:106 using next-generation sequencing.

Characterization of three novel HLA-DPA1 alleles bearing null, synonymous, and non-synonymous mutations.

Characterization of the novel HLA-DPA1*01:150 allele by sequencing-based typing.

HLA-DPA1*01:150 differs from HLA-DPA1*01:03:01:05 by one nucleotide substitution in codon 190 in exon 4.

Identification of a novel HLA-DPA1 allele, HLA-DPA1*02:102Q.

HLA-DPA1*02:102Q, a novel HLA class II allele detected by next-generation sequencing.