Human leukocyte antigen (HLA)-DRB1 allele polymorphisms and systemic sclerosis

Xu, Yijuan; Mo, Nanfang; Jiang, Zhiwen; Lu, Shaoming; Fu, Shien; Wei, Xinyan; Zhao, Dong; Xie, Zhibin; Jia, Wenxian; Liu, Jiayi; Wang, Xiao; Shi, Dongchen; Yang, Jiao; Liu, Chengwu; Yang, Xiaoli

doi:10.1080/14397595.2018.1519148

Cited by 13 publications

(9 citation statements)

References 42 publications

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“…The second cusp motif that we have studied was the 70-DERAA-74 sequence, which is coded by DRB1 alleles known to protect against RA and several other autoimmune conditions (118)(119)(120)(121)(122). An AP-based hypothesis to explain the contrasting effects of the SE and PE has been offered based on the charge of critical amino acid residues coded by these two functionally distinct alleles.…”

Section: The Mhc Cusp Theorymentioning

confidence: 99%

HLA-G and the MHC Cusp Theory

2022

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Human leukocyte antigens (HLA) are significant genetic risk factors in a long list of diseases. However, the mechanisms underlying these associations remain elusive in many cases. The best-characterized function of classical major histocompatibility complex (MHC) antigens is to allow safe presentation of antigenic peptides via a self/non-self-discrimination process. Therefore, most hypotheses to date have posited that the observed associations between certain HLA molecules and human diseases involve antigen presentation (AP). However, these hypotheses often represent inconsistencies with current knowledge. To offer answers to the inconsistencies, a decade ago we have invoked the MHC Cusp theory, postulating that in addition to its main role in AP, the MHC codes for allele-specific molecules that act as ligands in a conformationally-conserved cusp-like fold, which upon interaction with cognate receptors can trigger MHC-associated diseases. In the ensuing years, we have provided empirical evidence that substantiates the theory in several HLA-Class II-associated autoimmune diseases. Notably, in a recent study we have demonstrated that HLA-DRB1 alleles known to protect against several autoimmune diseases encode a protective epitope at the cusp region, which activates anti-inflammatory signaling leading to transcriptional and functional modulatory effects. Relevant to the topic of this session, cusp ligands demonstrate several similarities to the functional effects of HLA-G. The overall goal of this opinion article is to delineate the parallels and distinctive features of the MHC Cusp theory with structural and functional aspects of HLA-G molecules.

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Section: The Mhc Cusp Theorymentioning

confidence: 99%

HLA-G and the MHC Cusp Theory

2022

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“…For example, HLA-DRB1*03 is correlated to anti-carbamylated protein for rheumatoid arthritis (31). Allele polymorphism of HLA-DRB1 is associated with systemic sclerosis (32). The IFITM3 gene can promote bone metastasis of prostate cancer (33).…”

Section: Validation Of Hub Genes In Amd Cellular Modelsmentioning

confidence: 99%

Identification of differentially expressed and methylated genes and construction of a co-expression network in age-related macular degeneration

Liang¹,

Ma²,

Luo³

et al. 2022

Ann Transl Med

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Background: Age-related macular degeneration (AMD) is the leading cause of blindness for people over 50 years old worldwide. The purpose of this study was to identify differentially expressed and methylated genes (DEMGs) and construct a co-expression network for AMD.Methods: Microarray expression (GSE29801 dataset) and DNA methylation (GSE102952 dataset) profiles were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were analyzed between AMD retina tissues and normal retina tissues. A protein-protein interaction (PPI) network was constructed and hub genes were screened, followed by functional enrichment analysis. Then, weighted gene co-expression network analysis (WGCNA) was conducted.The ARPE-19 cells were maintained in a hypoxic state to construct an AMD cellular model. Enzyme-linked immunosorbent assay (ELISA) and the real-time qPCR (RT-qPCR) were performed for validation.Results: After overlapping, 16 hypermethylated and down-regulated genes and 15 hypomethylated and upregulated genes were identified for extramacular AMD. A total of 4 hub genes (LMNB2, EMD, HLA-A, and HLA-B) were screened for AMD in the extramacular retina. Furthermore, 13 hypermethylated and downregulated genes and 31 hypomethylated and up-regulated genes were identified for macular AMD. Among them, 11 hub genes (HLA-A,

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“…6 HLA-DRB1 is also associated with systemic lupus erythematosus (SLE) 7 and systemic sclerosis (SSc). 8 Moreover, correlations of HLA-DRB1 with cancer 9 and degenerative movement disorder have been identified. 10 A total of 151,858 HLA frequencies among 14,194,729 individuals was recorded in the Allele Frequency Net Database (AFDN, September 2022).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive research on the distribution of HLA‐DRB1 in Chinese populations

Fan

Huang

Zhang

et al. 2022

HLA

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By presenting antigen peptides, HLA‐DRB1 plays an important role in the immune system. However, the allele frequency of HLA‐DRB1 exon 2 across China has not been comprehensively studied, especially in minority populations. We sampled 3757 individuals from 59 population. The HLA‐DRB1 region from 212 to 463 bp (NM_002124.4 exon 2) in each population was sequenced by Sanger sequencing and genotyped via SBTengine® software, and the allele frequency was calculated by GenAlEx 6.5. Eighty‐two DRB1 alleles were identified. The expected heterozygosity of DRB1 was lower in the south than in the north, which was inconsistent with the Y chromosome and mitochondrial DNA results. The Mantel test and nonparametric correlation analysis showed that the correlations of the genetic distance with geographical distance and of DRB1 allele frequencies with latitude weakened after the southern and northern groups were considered separately. Principal coordinate analysis showed that populations speaking the same languages were not codistributed. Compared with other genetic markers, the distribution of DRB1 seems less affected by geographic distance and ethnic origin. Local factors such as gene flow with neighbouring populations, geographic isolation or natural selection are important forces shaping the DRB1 gene pool of local populations.

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Human leukocyte antigen (HLA)-DRB1 allele polymorphisms and systemic sclerosis

Abstract: DRB104:03, DRB108, DRB111, and DRB111:04 were associated with the risk of SSc. Additionally, DRB111 and DRB111:04 were association with ATAs.

Cited by 13 publications

References 42 publications

HLA-G and the MHC Cusp Theory

HLA-G and the MHC Cusp Theory

Identification of differentially expressed and methylated genes and construction of a co-expression network in age-related macular degeneration

Comprehensive research on the distribution of HLA‐DRB1 in Chinese populations

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Human leukocyte antigen (HLA)-DRB1 allele polymorphisms and systemic sclerosis

Abstract: DRB1*04:03, DRB1*08, DRB1*11, and DRB1*11:04 were associated with the risk of SSc. Additionally, DRB1*11 and DRB1*11:04 were association with ATAs.

Cited by 13 publications

References 42 publications

HLA-G and the MHC Cusp Theory

HLA-G and the MHC Cusp Theory

Identification of differentially expressed and methylated genes and construction of a co-expression network in age-related macular degeneration

Comprehensive research on the distribution of HLA‐DRB1 in Chinese populations

Contact Info

Product

Resources

About

Abstract: DRB104:03, DRB108, DRB111, and DRB111:04 were associated with the risk of SSc. Additionally, DRB111 and DRB111:04 were association with ATAs.