Brief Report: Influence of HLA–DRB1 Susceptibility Alleles on the Clinical Subphenotypes of Systemic Lupus Erythematosus in Koreans

So-Young, Bang; Choi, Ji Young; Park, Songree; Choi, Joon Yul; Hong, Seung Jae; Lee, Hye‐Soon; Choi, Chang-Woon; Bae, Sang Cheol

doi:10.1002/art.39539

Cited by 19 publications

(23 citation statements)

References 22 publications

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“…Moreover, the most protective, susceptible alleles were identical in both methods, illustrating the usefulness of the DISH method in looking for the most significant alleles in HLA fine-mapping studies. The observed associations of HLA-DRB1 alleles with RA or SLE in DISH-based and HMM-based approaches were supported by previous studies 15,16 that tested for the association for sequenced HLA-DRB1 alleles.…”

Section: Discussionsupporting

confidence: 76%

Understanding HLA associations from SNP summary association statistics

Lim

Bae

Kim

2019

Sci Rep

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Strong genetic associations in the region containing human leukocyte antigen (HLA) genes have been well-documented in various human immune disorders. Imputation methods to infer HLA variants from single nucleotide polymorphism (SNP) genotypes are currently used to understand HLA associations with a trait of interest. However, it is challenging for some researchers to obtain individual-level SNP genotype data or reference haplotype data. In this study, we developed and evaluated a new method, DISH (direct imputing summary association statistics of HLA variants), for imputing summary association statistics of HLA variants from SNP summary association statistics based on linkage disequilibria in Asian and European populations. Disease association Z scores in DISH were highly correlated with those from imputed HLA genotypes in null model datasets (r = 0.934 in Asians; r = 0.960 in Europeans). We applied DISH to two previous GWAS datasets in Asian systemic lupus erythematosus and European rheumatoid arthritis populations. There was a high correlation between Z scores in the DISH and HLA genotype imputations, showing the same disease-susceptible and protective alleles. This study illustrated the usefulness of the DISH method in understanding and identifying disease-associated HLA variants in human diseases while maintaining individual-level data security.

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Section: Discussionsupporting

confidence: 76%

Understanding HLA associations from SNP summary association statistics

Lim

Bae

Kim

2019

Sci Rep

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“…To date, the HLA-DRb1*03 and DRb1*15 alleles have consistently been reported to be associated with SLE. Previous studies have shown that HLA-DRb1*15 is associated with SLE in Japanese, Brazilian, Hungarian, Taiwanese and Korean populations, 24,28,29,32,45,46 whereas the HLA-DRB1*03 allele was associated with Hungarian, Taiwanese, Egyptian, Latin American and UK-European Caucasian individuals. 25,28,29,31,32 The association of the HLA-DRb1*04 allele with SLE was reported in Swedish, European Caucasian and Egyptian populations.…”

Section: Discussionmentioning

confidence: 94%

The influence of functional polymorphic positions ofHLA-DRβ1molecules on risk for South Indian systemic lupus erythematosus patients

Katkam

Rajasekhar

Kutala

2018

Lupus

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The aim of this case-control study was to investigate the association of human leukocyte antigen (HLA) Class II alleles with the susceptibility and phenotypic heterogeneity in systemic lupus erythematosus (SLE) in South Indian patients. A total of 439 individuals (212 SLE cases and 227 age- and ethnicity-matched controls) were included in the study. The genotyping of HLA-DRβ1 and - DQβ1 was conducted by the PCR-SSP method. HLA-DRβ1*07 was significantly associated with SLE (OR: 2.02; 95% CI: 1.34-3.04, p = 1.50 × 10, p = 1.95 × 10), whereas the DRβ1*14 allele was negatively associated with SLE (OR: 0.49; 95% CI: 0.31-0.76, p = 1.70 × 10, p = 0.221). In addition, the HLA-DRβ1*07/15 genotype tended to be positively associated with SLE (OR: 3.23, 95% CI: 1.57-6.63, p = 0.0009). Amino acid residues residing in the peptide-binding pocket of HLA-DRβ1 play a significant role in peptide recruitment and antigen presentation. Our results demonstrated that amino acid glycine 11 (OR: 2.11, 95% CI: 1.42-3.12, p = 0.00093), tyrosine 13 (OR: 2.11, 95% CI: 1.42-3.12, p = 0.00062) and glutamine 74 (OR: 2.11, 95% CI: 1.42-3.12, p = 0.00077) showed a significant positive association with SLE. Certain haplotype combinations, DRB1*07-DQβ1*03 (OR: 2.21; 95% CI:1.29-3.79, p = 0.06, p = 0.00036) and DRβ1*07-DQβ1*05 (OR: 2.51, 95% CI: 1.34-4.71, p = 0.07, p = 0.00039), had positive associations whereas DRβ1*14-DQβ1*03 (OR: 0.14, 95% CI: 0.061-0.36, p = 2.34 × 10, p = 1.30 × 10) were found to have a significant negative association with SLE. So far, the present study is the first attempt to investigate the association of HLA-DRβ1 and - DQβ1 allele, genotype and haplotype combinations with the risk of SLE in South Indian patients. In conclusion, the HLA-DRβ1*07 allele is associated with risk of SLE whereas a protective association of HLA-DRβ1*14 alleles with SLE was observed.

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“…Some loci have been associated to increase the risk of SLE; for example, complement components C1q and C4, major histocompatibility complex (especially the human leucocyte antigen, class II), T cell receptor and many cytokines (IL-6, IL-27, IL-12, IL-23) [5,6]. At the same time, some are typically related to other autoimmune diseases as diabetes or rheumatoid arthritis (RA) (PTPN22 and STAT4) [7].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles as Therapeutic Agents in Systemic Lupus Erythematosus

Perez-Hernandez¹,

Redón²,

Cortés³

2017

IJMS

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Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that affects multiple organs. Currently, therapeutic molecules present adverse side effects and are only effective in some SLE patient subgroups. Extracellular vesicles (EV), including exosomes, microvesicles and apoptotic bodies, are released by most cell types, carry nucleic acids, proteins and lipids and play a crucial role in cell-to-cell communication. EVs can stimulate or suppress the immune responses depending on the context. In SLE, EVs can work as autoadjuvants, enhance immune complex formation and maintaining inflammation state. Over the last years, EVs derived from mesenchymal stem cells and antigen presenting cells have emerged as cell-free therapeutic agents to treat autoimmune and inflammatory diseases. In this review, we summarize the current therapeutic applications of extracellular vesicles to regulate immune responses and to ameliorate disease activity in SLE and other autoimmune disorders.

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Brief Report: Influence of HLA–DRB1 Susceptibility Alleles on the Clinical Subphenotypes of Systemic Lupus Erythematosus in Koreans

Cited by 19 publications

References 22 publications

Understanding HLA associations from SNP summary association statistics

Understanding HLA associations from SNP summary association statistics

The influence of functional polymorphic positions ofHLA-DRβ1molecules on risk for South Indian systemic lupus erythematosus patients

Extracellular Vesicles as Therapeutic Agents in Systemic Lupus Erythematosus

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