Association Analysis of the MHC in Lupus Nephritis

Xu, Ricong; Li, Qibin; Liu, Rongjun; Shen, Juan; Li, Ming; Zhao, Ming‐Hui; Wang, Meng; Liao, Qijun; Mao, Haiping; Z, Li; Zhou, Na; Yin, Peiran; Li, Yue; Tang, Xueqing; Wu, Tian Shung; Zhong, Zhong; Wang, Yan; Ai, Zhen; Wang, Ou; Chen, Nan; Yang, Xiaoqin; Fang, Junbin; Fu, Ping; J, Gu; Ye, Kun; Chen, Jian; Dai, Lie; Liu, Huafeng; Liu, Zhangsuo; Liao, Yunhua; Wan, Jianxin; Ding, Guohua; Zhao, Jinghong; Zhang, Hao; S, Fu; Sun, Liangdan; Zhang, Xuejun; Yang, Huanming; Wang, Jian; Wang, Jun; Liu, Jing; Li, Yingrui; Yu, Xueqing

doi:10.1681/asn.2016121331

Cited by 23 publications

(11 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A comprehensive sequencing analysis of the whole MHC region of a large LN cohort showed that HLA-DRB1 amino acid 11 is one of the five functional risk variants for LN within MHC regions. These independent risk variants also suggest that the risk of development of LN could be due to aberration in peptide presentation by MHC class 1 and 2 molecules to T cells and sex hormone dysregulation ( 75 ). Another source presumed that three amino acid positions (11, 13, and 26) located at the HLA-DRB1 epitope-binding groove establish a pathogenic structure in LN patients ( 76 ).…”

Section: Discussionmentioning

confidence: 99%

HLA-DRB1*04 as a Risk Allele to Systemic Lupus Erythematosus and Lupus Nephritis in the Malay Population of Malaysia

et al. 2021

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease afflicting multiple organs. Lupus nephritis (LN) is a serious complication of SLE and remains a major cause of mortality and morbidity. Curative therapy remains unavailable as etiology from genetic and environmental factors is still unclear. The present study was conducted to elucidate the link between HLA-DRB1 gene polymorphisms with SLE and LN through clinical and laboratory/biological presentations in a population of Malaysian Malay females with SLE. A total of 100 Malay female SLE patients inclusive of 70 SLE patients without LN and 30 patients with LN were included in this study. HLA-DRB1 allele examination in SLE patients was performed using PCR-SSO, and the alleles' frequencies were compared with 951 publicly available datasets representing Malay healthy controls in Malaysia. Cytokines and free radical levels were detected by ELISA and bead-based multiplexed Luminex assays. The association between HLA-DRB1 alleles with clinical and serological manifestations and immune mediators was analyzed using different statistical approaches whenever applicable. Our study showed that HLA-DRB1*0405, HLA-DRB1*1502, and HLA-DRB1*1602 were associated with the increased risk of SLE while HLA-DRB1*1201 and HLADRB1*1202 alleles were associated with a lower risk of SLE development. Furthermore, HLA-DRB1*04 showed significant association to LN and arthritis while HLA-DRB1*15 was significantly associated with oral ulcer in Malay SLE patients. Association analysis of HLA-DRB1*04 with clinical and biological factors revealed that HLA-DRB1*04 was significantly associated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-nuclear antibody (ANA), C-reactive protein (CRP) in the blood, and total protein in the urine. SLE carriers with the HLA-DRB1*04 allele were significantly correlated to the increased levels of cytokines (IFN-y, GM-CSF, IL-17F, IL-18, IL-21, and VEGF) and were significantly showing negative correlation to IL-5 and free radicals (LPO and catalase enzyme) levels compared to SLE carriers without HLA-DRB1*04 allele. The results suggested that disease severity in SLE may be determined by HLA-DRB1 alleles. The risk of HLA-DRB1*04 allele with LN was supported by the demonstration of an intense inflammatory response in Malay SLE patients in Malaysia. More studies inclusive of a larger and multiple SLE cohorts in the future are warranted to validate these findings.

show abstract

Section: Discussionmentioning

confidence: 99%

HLA-DRB1*04 as a Risk Allele to Systemic Lupus Erythematosus and Lupus Nephritis in the Malay Population of Malaysia

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Alleles at the same HLA locus, which may differ structurally by a few nucleotides, can result in completely different disease susceptibility or resistance profiles (Xue et al, 2018). This explains the differential expression of the four HLA genes we identified in the SLE and LN datasets, with genetic polymorphisms resulting in systemic and local pathological changes (Xu et al, 2017). IRF8 is a member of the interferon regulatory factor (IRF) family that regulates the signaling pathway for Toll-like receptors (Salem et al, 2020).…”

Section: Disscussionmentioning

confidence: 92%

Prioritization of Diagnostic and Prognostic Biomarkers for Lupus Nephritis Based on Integrated Bioinformatics Analyses

Chen

Lan

et al. 2021

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Lupus nephritis (LN) is an important driver of end-stage renal disease (ESRD). However, few biomarkers are available for evaluating the diagnosis and prognosis of LN. For this study, we downloaded microarray data of multiple LN expression profiles from the GEO database. We used the WGCNA and R limma packages to identify LN hub genes and differentially-expressed genes (DEGs). We identified nine co-DEGs in the intersection with LN-related genes from the Genecards database. We found DEGs that are primarily associated with immune-related functions and pathways (including with the complement pathway, primary immunodeficiency markers, and MHC-like protein complexes) through our comprehensive GSEA, GO, and KEGG enrichment analyses. We used other LN and SLE validation datasets and discovered six explicitly expressed co-DEGs: HLA-DMA, HLA-DPA1, HLA-DPB1, HLA-DRA, IL10RA, and IRF8 in the LN set; ROC and Precision-Recall curve analyses revealed that these six genes have a good diagnostic efficacy. The correlation analysis with prognostic data from the Nephroseq database indicates that the differential expression of these co-DEGs is associated with a low glomerular filtration rate in that cohort. Additionally, we used a single-cell LN database of immune cells (for the first time) and discovered these co-DEGs to be predominantly distributed in different types of macrophages and B cells. In conclusion, by integrating multiple approaches for DEGs discovery, we identified six valuable biomarkers that are strongly correlated with the diagnosis and prognosis of LN. These markers can help clarify the pathogenesis and improve the clinical management of LN.

show abstract

“…Several MHC haplotypes (HLA-DR2, HLA-DR3,and HLA-DR15) have been identified to increase the risk of SLE and lupus nephritis (Graham et al 2007;Chung et al 2014;Niu et al 2015). Until now, the role of these HLA molecules has been linked to comprised immune tolerance to nuclear autoantigens (Yellin et al 1997;Clynes et al 1998;Goodnow 2007;Xu et al 2017). However, studies suggest that epithelial cells such as podocytes and renal tubular cells also express HLA molecules and even regulate T cell activation (Wuthrich et al 1989;Frasca et al 1998;Banu and Meyers 1999;Yuan et al 2020).…”

Section: Lupus Nephritismentioning

confidence: 99%

Kidney organoid systems for studies of immune-mediated kidney diseases: challenges and opportunities

et al. 2021

View full text Add to dashboard Cite

Acute and chronic kidney diseases are major contributors to morbidity and mortality in the global population. Many nephropathies are considered to be immune-mediated with dysregulated immune responses playing an important role in the pathogenesis. At present, targeted approaches for many kidney diseases are still lacking, as the underlying mechanisms remain insufficiently understood. With the recent development of organoids—a three-dimensional, multicellular culture system, which recapitulates important aspects of human tissues—new opportunities to investigate interactions between renal cells and immune cells in the pathogenesis of kidney diseases arise. To date, kidney organoid systems, which reflect the structure and closer resemble critical aspects of the organ, have been established. Here, we highlight the recent advances in the development of kidney organoid models, including pluripotent stem cell-derived kidney organoids and primary epithelial cell-based tubuloids. The employment and further required advances of current organoid models are discussed to investigate the role of the immune system in renal tissue development, regeneration, and inflammation to identify targets for the development of novel therapeutic approaches of immune-mediated kidney diseases.

show abstract

Association Analysis of the MHC in Lupus Nephritis

Cited by 23 publications

References 50 publications

HLA-DRB1*04 as a Risk Allele to Systemic Lupus Erythematosus and Lupus Nephritis in the Malay Population of Malaysia

HLA-DRB1*04 as a Risk Allele to Systemic Lupus Erythematosus and Lupus Nephritis in the Malay Population of Malaysia

Prioritization of Diagnostic and Prognostic Biomarkers for Lupus Nephritis Based on Integrated Bioinformatics Analyses

Kidney organoid systems for studies of immune-mediated kidney diseases: challenges and opportunities

Contact Info

Product

Resources

About