Association of Variants in <i>CCR6</i> With Susceptibility to Lupus Nephritis in Chinese

Zhou, Xu‐jie; Mu, Rong; Li, Chun; Nath, Swapan K.; Zhang, Yuemiao; Qi, Yuanyuan; Li, Zhanguo; Zhao, Ming‐Hui; Zhang, Hong

doi:10.1002/art.39268

Cited by 13 publications

(11 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A significant association between CCR6 gene polymorphism and susceptibility to LN in SLE patients has also been reported ( Zhou et al, 2015 ). Furthermore, it has been identified that CCR6 chemokine expressed by the effector/memory CD4 + T cells plays a role tissue damage in SLE patients, including LN or neuropsychiatric SLE patients, and probably functions through CCR6/CCL20 axis at the inflamed sites ( Koga et al, 2016 ).…”

Section: Discussionmentioning

confidence: 96%

“…It has also been demonstrated that pathogenic Th17 cells expressing CCR6 play a key role in accelerating organ injury in animal models of glomerulonephritis ( Turner et al, 2010 ) and arthritis ( Hirota et al, 2007 ). In addition, a genetic link has also been reported between CCR6 gene polymorphisms and LN susceptibility ( Zhou et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CCR6⁺ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status

Wang

Jiang

et al. 2018

PeerJ

View full text Add to dashboard Cite

BackgroundSystemic lupus erythematosus (SLE) disease has been shown to be associated with the generation of multiple auto-antibodies. Among these, anti-dsDNA antibodies (anti-DNAs) are specific and play a pathogenic role in SLE. Indeed, anti-DNA+ SLE patients display a worse disease course. The generation of these pathogenic anti-DNAs has been attributed to the interaction between aberrant T helper (Th) cells and autoimmune B cells. Thus, in this study we have investigated whether CCR6+Th cells have the ability to differentiate SLE patients based on anti-DNA status, and if their distribution has any correlation with disease activity.MethodsWe recruited 25 anti-DNA+ and 25 anti-DNA− treatment-naive onset SLE patients, matched for various clinical characteristics in our nested matched case-control study. CCR6+ Th cells and their additional subsets were analyzed in each patient by flow cytometry.ResultsAnti-DNA+ SLE patients specifically had a higher percentage of Th cells expressing CCR6 and CXCR3. Further analysis of CCR6+ Th cell subsets showed that anti-DNA+ SLE patients had elevated proportions of Th9, Th17, Th17.1 and CCR4/CXCR3 double-negative (DN) cells. However, the proportions of CCR6− Th subsets, including Th1 and Th2 cells, did not show any association with anti-DNA status. Finally, we identified a correlation between CCR6+ Th subsets and clinical indicators, specifically in anti-DNA+ SLE patients.ConclusionsOur data indicated that CCR6+ Th cells and their subsets were elevated and correlated with disease activity in anti-DNA+ SLE patients. We speculated that CCR6+ Th cells may contribute to distinct disease severity in anti-DNA+ SLE patients.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

CCR6⁺ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status

Wang

Jiang

et al. 2018

PeerJ

View full text Add to dashboard Cite

show abstract

“…Th17 cells expressing CCR6 appeared to be more pathogenic and accelerate organ impairment after renal injury 24 and arthritis 25 in various animal models. In addition, a genetic association has also been reported between CCR6 gene polymorphisms and susceptibility to lupus nephritis (LN) 26 . However, there have been few studies highlighting the relationship between CCR6 + Th cell sub-populations and SLE, especially in patients with organ impairment.…”

Section: Introductionmentioning

confidence: 99%

Elevated levels of CCR6+ T helper 22 cells correlate with skin and renal impairment in systemic lupus erythematosus

Wang

Jiang

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is an autoimmune disease with a variety of pathological features. Our study investigated the potential role of CCR6+ T cells in organ impairment of SLE patients. We analyzed CCR6+/− T cell subset populations and compared the concentrations of IL-22, IFN-γ, TNF-α, and IL-17A cytokines in 67 patients with newly diagnosed SLE and 26 healthy controls. We found that SLE patients had elevated percentages of CCR6+ T, CCR6+ Th22, Th17, Th17.1, and CCR6− Th2 cell subsets, along with increased concentrations of IL-22, IFN-γ, TNF-α, and IL-17 cytokines. Higher levels of CCR6+ T and CCR6+ Th22 cells, along with plasma IL-22 were observed in SLE patients with sole skin and/or renal impairment. The percentage of Th22 cells also correlated with Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) and IgG levels, and inversely correlated with C3 levels in SLE patients with sole skin impairment. SLE patients with sole renal impairment showed a correlation between the percentage of Th22 cells and ESR levels. Our data indicated that CCR6+ Th22 cells may contribute to the pathogenesis of new onset SLE patients with skin or renal impairment, and CCR6 may, thus, be a possible therapeutic target for SLE treatment.

show abstract

“…At last, 21 SNPs representing 16 SLE risk loci were included and genotyping was performed using the MassArray system from Sequenom. For replications of selected two SNPs in additional independent cohort, TaqMan assays were conducted as previously reported67.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic studies have pointed out partial sharing of mechanisms of these two diseases. In our previous studies, we identified CFH, HLA-DRA, HLA-DRB1, PXK, BLK, UBE2L3 and MTMR3 as shared loci between IgAN and systemic lupus erythematosus (SLE)/LN based on GWAS on Chinese populations, highlighting pathways including MHC class-II antigen presentation, complement regulation, signaling by the BCR, autophagy, and ubiquitin/proteasome-dependent degradation in the pathogenesis of these two complex diseases456789. The degree of shared genes between IgAN and SLE is substantial, but is likely to be still an underestimate because we just included candidate variants with genome-wide significance in respective GWASs and most of involved GWASs were conducted in peoples with Caucasian ancestry.…”

mentioning

confidence: 99%

Novel identified associations of RGS1 and RASGRP1 variants in IgA Nephropathy

Zhou

Nath

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

Known susceptibility loci together can only explain about 6–8% of the disease heritability of IgA nephropathy (IgAN), suggesting that there are still a large number of genetic variants remained to be discovered. We previously identified IgAN and systemic lupus erythematosus (SLE)/lupus nephritis (LN) shared many loci based on GWAS on Chinese populations. The more recent study with high-density genotyping of immune-related loci in individuals with Asian ancestry identified 10 new and 6 suggestive loci in SLE. In the current study, we thus included all the lead SNPs from these 16 loci reported, and firstly tested their associations in 1,248 patients with sporadic IgAN, 737 patients with LN and 1,187 controls. Significant associations identified in IgAN were replicated in additional 500 patients and 2372 controls. rs12022418 in RGS1 (p = 3.0 × 10−6) and rs7170151 in RASGRP1 (p = 1.9 × 10−5) showed novel associations in IgAN. Compared to SNPs that were in LD with them, the associated variants showed higher potential of regulatory features by affecting gene expression. And systemic evaluation of GWAS data supported the pleiotropic effects of RGS1 and RASGRP1 variants in mediating human complex diseases. In conclusion, novel risk loci shared between IgAN and SLE/LN were identified, which may shed new light to exploit the potential pathogenesis for those two diseases.

show abstract

Association of Variants in CCR6 With Susceptibility to Lupus Nephritis in Chinese

Cited by 13 publications

References 10 publications

CCR6⁺ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status

CCR6⁺ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status

Elevated levels of CCR6+ T helper 22 cells correlate with skin and renal impairment in systemic lupus erythematosus

Novel identified associations of RGS1 and RASGRP1 variants in IgA Nephropathy

Contact Info

Product

Resources

About

Association of Variants in CCR6 With Susceptibility to Lupus Nephritis in Chinese

Cited by 13 publications

References 10 publications

CCR6+ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status

CCR6+ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status

Elevated levels of CCR6+ T helper 22 cells correlate with skin and renal impairment in systemic lupus erythematosus

Novel identified associations of RGS1 and RASGRP1 variants in IgA Nephropathy

Contact Info

Product

Resources

About

CCR6⁺ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status

CCR6⁺ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status