A novel HLA-C*03 variant, HLA-C*03:620, identified in a Chinese individual.

HLA-C*03:620 differs from the HLA-C*03:04:01:02 allele by one nucleotide substitution in the exon 3.

Discovery of the novel HLA-C*12:02:53 allele in a Taiwanese individual.

Nucleotide substitution in codon 238 of HLA-C*12:02:02:01 results in a novel allele, HLA-C*12:02:53.

Characterisation of the novel HLA-C*15:274 allele using short and long-read sequencing technologies.

The novel HLA-C*15:274 allele, first described in a potential bone marrow donor from Brazil.

Insights into PCSK9-LDLR Regulation and Trafficking via the Differential Functions of MHC-I Proteins HFE and HLA-C.

PCSK9 is implicated in familial hypercholesterolemia via targeting the cell surface PCSK9-LDLR complex toward lysosomal degradation. The M2 repeat in the PCSK9's C-terminal domain is essential for its extracellular function, potentially through its interaction with an unidentified "protein X". The M2 repeat was recently shown to bind an R-x-E motif in MHC-class-I proteins (implicated in the immune system), like HLA-C, and causing their lysosomal degradation. These findings suggested a new role of PCSK9 in the immune system and that HLA-like proteins could be "protein X" candidates. However, the participation of each member of the MHC-I protein family in this process and their regulation of PCSK9's function have yet to be determined. Herein, we compared the implication of MHC-I-like proteins such as HFE (involved in iron homeostasis) and HLA-C on the extracellular function of PCSK9. Our data revealed that the M2 domain regulates the intracellular sorting of the PCSK9-LDLR complex to lysosomes, and that HFE is a new target of PCSK9 that inhibits its activity on the LDLR, whereas HLA-C enhances its function. This work suggests the potential modulation of PCSK9's functions through interactions of HFE and HLA-C.

Characterisation of the novel HLA-C*08:275 allele, first identified in a Brazilian individual.

The novel HLA-C*08:275 allele, first described in a potential bone marrow donor from Brazil.

The novel HLA-C*03:652 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*03:652 differs from the HLA-C*03:04:01:01 by one nucleotide in exon 3.

The novel HLA-C*14:155 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*14:155 differs from HLA-C*14:02:01:01 by one nucleotide in exon 1.

Identification of five new HLA-C alleles by next-generation sequencing.

Five novel HLA-C alleles detected by next-generation sequencing: HLA-C*02:02:73, -C*03:04:106, -C*06:382, -C*07:1114Q and -C*12:408.

Detection of the HLA-C*07:04:29 allele in a Chinese individual.

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

Identification of the novel HLA-C allele, HLA-C*07:02:150.

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

The novel HLA-C*07:02:147 allele characterised by two different sequencing-based typing techniques.

The novel allele HLA-C*07:02:147 differs from HLA-C*07:02:01:01 by one synonymous nucleotide substitution in exon 2.

The novel HLA-C*03:94:02 allele identified by next-generation sequencing in a Chinese individual.

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

Detection of the novel HLA-B*55:01:31, HLA-C*07:1113 alleles and confirmation of HLA-C*12:392.

Novel HLA-B*55:01:31, HLA-C*07:1113 alleles and confirmatory HLA-C*12:392 allele were detected during the HLA typing process.

Identification of the novel HLA-C allele, HLA-C*12:351Q, using next-generation sequencing.

The novel allele HLA-C*12:351Q differs from HLA-C*12:02:02:01 by a single nucleotide deletion in exon 5.

Recognition of the HLA-C*07:359 allele in Taiwanese individuals.

One nucleotide substitution in codon 264 of HLA-C*07:02:01:01 results in a novel allele, HLA-C*07:359.

Characterization of the novel HLA-C*06:376N allele by Pacific Biosciences HiFi sequencing in a Chinese individual.

HLA-C*06:376N differs from HLA-C*06:02:01:01 by seven nucleotide changes in exon 2, intron 2, and exon 3.

Novel genetic variants of HLA gene associated with Thai Behcet's disease (BD) patients using next generation sequencing technology.

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 (41.1%), vascular (35.7%), skin (55.4%), CNS (5.4%), and GI system (10.7%) involvement. This study found associations between BD and HLA-A*26:01:01 (OR 3.285, 95% CI 1.135-9.504, P-value 0.028), HLA-B*39:01:01 (OR 6.176, 95% CI 1.428-26.712, P-value 0.015), HLA-B*51:01:01 (OR 3.033, 95% CI 1.135-8.103, P-value 0.027), HLA-B*51:01:02 (OR 6.176, 95% CI 1.428-26.712, P-value 0.015), HLA-C*14:02:01 (OR 3.485, 95% CI 1.339-9.065, P-value 0.01), HLA-DRB1*14:54:01 (OR 1.924, 95% CI 1.051-3.522, P-value 0.034), and HLA-DQB1*05:03:01 (OR 3.00, 95% CI 1.323-6.798, P-value 0.008). However, after Bonferroni correction none of these alleles were found to be associated with BD. In haplotype analysis, we found a strong linkage disequilibrium in HLA-B*51:01:01, HLA-C*14:02:01 (P-value 0.0, Pc-value 0.02). Regarding the phenotype, a significant association was found between HLA-DRB1*14:54:01 (OR 11.67, 95% CI 2.86-47.57, P-value 0.001) and BD with ocular involvement, apart from this, no distinct phenotype-HLA association was documented. In summary, our study identifies specific HLA associations in BD. Although limited by a small sample size, we acknowledge the need for further investigation into HLA relationships with CNS, GI, and neurological phenotypes in the Thai population.

Polymorphisms in the CD6-ALCAM axis may modulate psoriasis risk and outcomes.

The fact that CD6, along with its ligand - ALCAM, plays a role in regulating T cell activation makes the genes encoding these molecules promising candidates for research in T cell-mediated diseases such as psoriasis vulgaris (PsV). Our study aimed to determine whether CD6 (rs17824933C>G, rs11230563C>T and rs12360861G>A) and ALCAM (rs6437585C>T, rs11559013G>A) polymorphisms may affect psoriasis susceptibility and severity (assessed by Psoriasis Area and Severity Index (PASI)). Moreover, the presence of HLA-C*06:02, the strongest psoriasis risk factor in the Caucasian population, was also investigated. 273 patients diagnosed with psoriasis vulgaris and 256 blood donors with no history of PsV or other dermatoses were included in this study. Genotyping of the investigated polymorphisms was carried out using the allelic discrimination method with the application of TaqMan SNP Genotyping Assays. We observed the association of rs17824933G allele with a higher psoriasis risk in HLA-C*06:02(+) individuals (CG + GG vs CC, OR = 1.87, CI95% = 1.03; 3.37, p = 0.0350). Furthermore, we found a difference in average PASI score among groups of patients divided according to the number of CD6 and ALCAM polymorphic sites with minor alleles (F2,173 = 6.159, p = 0.0026). Collectively, our findings suggest that polymorphisms of CD6-ALCAM axis genes may modulate psoriasis risk and outcomes.

HLA-B and C Expression Contributes to COVID-19 Disease Severity within a South African Cohort.

Globally, SARS-CoV-2 has negatively impacted many lives and industries due to its rapid spread, severe outcomes, and the need for the implementation of lockdown strategies across the world. SARS-CoV-2 disease severity varies among different populations. Host genetics have been associated with various diseases, and their ability to alter disease susceptibility and severity. In addition, Human Leukocyte Antigen (HLA) expression levels and alleles vary significantly among ethnic groups, which might impact the host's response to SARS-CoV-2. Our previous study highlighted that HLA-A might have an effect on COVID-19 disease severity across ethnicities. Therefore, in this study, we aim to examine the effect of HLA-B and C expression levels on COVID-19 disease severity. To achieve this, we used real-time PCR to measure the HLA mRNA expression levels of SARS-CoV-2-infected individuals from a South African cohort and compared them across ethnic groups, disease outcomes, gender, comorbidities, and age. Our results show (1) that the effect of HLA-B mRNA expression levels was associated with differences in disease severity when we compare symptomatic vs. asymptomatic (p < 0.0001). While HLA-C mRNA expression levels were not associated with COVID-19 disease severity. (2) In addition, we observed that HLA-B and HLA-C mRNA expression levels were significantly different between South African Black individuals and South African Indian individuals (p < 0.0001, p < 0.0001). HLA-B mRNA expression levels among symptomatic South African Black individuals were significantly higher than symptomatic South African Indian individuals (p < 0.0001). In addition, the HLA-B mRNA expression levels of symptomatic South African Black individuals were significantly higher than asymptomatic South African Black individuals (p > 0.0001). HLA-C mRNA expression levels among symptomatic South African Black individuals were significantly higher than among symptomatic South African Indian individuals (p = 0.0217). (3) HLA-C expression levels were significantly different between males and females (p = 0.0052). In addition, the HLA-C expression levels of asymptomatic males are higher than asymptomatic females (p = 0.0375). (4) HLA-B expression levels were significantly different between individuals with and without comorbidities (p = 0.0009). In addition, we observed a significant difference between individuals with no comorbidities and non-communicable diseases (p = 0.0034), in particular, hypertension (p = 0.0487). (5) HLA-B expression levels were significantly different between individuals between 26-35 and 56-65 years (p = 0.0380). Our work is expected to strengthen the understanding of the relationship between HLA and COVID-19 by providing insights into HLA-B and C expression levels across ethnic populations in South Africa among COVID-19-symptomatic and asymptomatic individuals. Our results highlight that HLA-B mRNA expression levels contribute to COVID-19 severity as well as variation in ethnicities associated with COVID-19. Further studies are needed to examine the effect of HLA expression levels across various ethnic groups with contributing factors.