Investigation of C1-complex regions reveals new C1Q variants associated with protection from systemic lupus erythematosus, and affect its transcript abundance

Guo, Jianping; Gao, Yu; Wang, Yuxuan; Zou, Yundong; Du, Yan; Luo, Cainan; Shi, Yuhang; Yang, Yue; Wu, Xinyu; Su, Yin; Wu, Lijun; Chen, Shi; Li, Zhanguo

doi:10.1038/s41598-018-26380-x

Cited by 11 publications

(6 citation statements)

References 23 publications

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“…C1Q deficiency likely results in the emergence of an immunodeficient state, which causes abnormal physiological and pathological processes. For instance, several autoimmune diseases are strongly associated with C1Q defects, such as glomerulonephritis 38 and systemic lupus erythematosus (SLE), 39 and C1Q deficiency is by far the most penetrating cause of the disease. [40][41][42][43] Thus, the downregulation of C1Q in metastatic OS patients likely results in abnormalities in physiological processes and serious outcomes.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Implications of the Complement Protein C1Q and Its Correlation with Immune Infiltrates in Osteosarcoma

Huang¹,

Tan²,

Zheng³

et al. 2021

OTT

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Background Osteosarcoma (OS) is the most widespread bone tumour among childhood cancers, and distant metastasis is the dominant factor in poor prognosis for patients with OS. Therefore, it is necessary to identify new prognostic biomarkers for identifying patients with aggressive disease. Methods Two OS datasets (GSE21257 and GSE33383) were downloaded from the Gene Expression Omnibus (GEO) and subsequently subjected to weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis (DGE) to screen candidate genes. A prognostic model was constructed using OS data derived from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program to further screen key genes and perform gene ontology (GO) analysis. The prognostic values of key genes were assessed using the Kaplan–Meier (KM) plotter. The GEO dataset was used for immune infiltration analysis and association analysis of key genes. In addition, quantitative real-time polymerase chain reaction (qRT-PCR) was employed to validate the expression levels of potentially crucial genes in OS cell lines. Results In the present study, we found 114 genes with a highly significant correlation in the module and 44 downregulated genes; 25 candidate genes overlapped in the two parts of the genes. Among these, three key genes, C1QA , C1QB , and C1QC , were the most significant hub genes, which had the highest node degrees, were clustered into one group, and implicated in most significant biological processes (regulation of immune effector process). Moreover, these three key genes were negatively associated with the prognosis of OS and positively associated with three immune cells (follicular helper T cells, memory B cells, and CD8 T cells). Additionally, compared to non-metastatic OS cell lines, the expression of three key genes was significantly downregulated in metastatic OS cell lines. Conclusion Our results revealed that three key genes ( C1QA , C1QB , and C1QC) were implicated in tumour immune infiltration and may be promising biomarkers for predicting metastasis and prognosis of patients with OS.

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Section: Discussionmentioning

confidence: 99%

Prognostic Implications of the Complement Protein C1Q and Its Correlation with Immune Infiltrates in Osteosarcoma

Huang¹,

Tan²,

Zheng³

et al. 2021

OTT

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“…Deficiency of C1q is strongly associated with SLE. Over 90% of patients with monogenetic mutations in C1q develop an SLE-like syndrome ( 12 , 13 ). C1q binds to and promotes phagocytosis of apoptotic cellular debris.…”

Section: Introductionmentioning

confidence: 99%

Isolevuglandins disrupt PU.1-mediated C1q expression and promote autoimmunity and hypertension in systemic lupus erythematosus

Patrick¹,

Visitación²,

Krishnan³

et al. 2022

JCI Insight

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We describe a mechanism responsible for systemic lupus erythematosus (SLE). In humans with SLE and in 2 SLE murine models, there was marked enrichment of isolevuglandin-adducted proteins (isoLG adducts) in monocytes and dendritic cells. We found that antibodies formed against isoLG adducts in both SLE-prone mice and humans with SLE. In addition, isoLG ligation of the transcription factor PU.1 at a critical DNA binding site markedly reduced transcription of all C1q subunits. Treatment of SLE-prone mice with the specific isoLG scavenger 2-hydroxybenzylamine (2-HOBA) ameliorated parameters of autoimmunity, including plasma cell expansion, circulating IgG levels, and anti-dsDNA antibody titers. 2-HOBA also lowered blood pressure, attenuated renal injury, and reduced inflammatory gene expression uniquely in C1q-expressing dendritic cells. Thus, isoLG adducts play an essential role in the genesis and maintenance of systemic autoimmunity and hypertension in SLE.

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“…Second, various AIDs may have mild or severe effects on the body. For instance, systemic lupus erythematosus (SLE) can affect nearly all organs and produces multiple autoantibodies [42] , whereas psoriasis causes relatively minor impairments in other systems.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of immune checkpoint inhibitors in advanced cancer patients with autoimmune disease: A meta-analysis

Cai

Huo

Zhu

et al. 2022

Human Vaccines & Immunotherapeutics

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Background: Cancer patients with autoimmune disease (AID) are usually excluded from clinical trials involving immune checkpoint inhibitors (ICIs); their safety and effectiveness remain uncertainty.Methods: The available electronic databases were systematically searched. We recorded the incidence of immune-related adverse events (irAEs), progression-free survival (PFS), and overall survival (OS) of included studies.Results: This meta-analysis included 11 studies comprising 5489 participants. The pooled risk ratio (RR) for any grade and grade ≥3 irAEs was 1.79 (95% con dence interval [CI]: 1.31-2.45) and 1.58 (95% CI: 1.06-2.36), respectively. The irAEs in the same system as the AID were referred to as AID-homogeneous irAEs, otherwise known as AID-heterogeneous irAEs. Subgroup analysis found that the higher risk of AID-homogeneous irAEs contributed to the higher risk of overall irAEs among patients with AID. The pooled hazard ratio (HR) for PFS and OS was 1.09 (95% CI: 0.96-1.25) and 1.10 (95% CI: 0.68-1.77), respectively. The results of PFS and OS subgroup analyses matched the overall results.Conclusion: patients with AID had a signi cantly higher risk of developing any grade and ≥3 grade irAEs under ICI therapy, speci cally AIDhomogeneous irAEs; however, AID-heterogeneous irAEs were higher among patients with AID than in those without. No statistically signi cant differences in PFS and OS were observed between two groups.

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Investigation of C1-complex regions reveals new C1Q variants associated with protection from systemic lupus erythematosus, and affect its transcript abundance

Cited by 11 publications

References 23 publications

Prognostic Implications of the Complement Protein C1Q and Its Correlation with Immune Infiltrates in Osteosarcoma

Prognostic Implications of the Complement Protein C1Q and Its Correlation with Immune Infiltrates in Osteosarcoma

Isolevuglandins disrupt PU.1-mediated C1q expression and promote autoimmunity and hypertension in systemic lupus erythematosus

Safety and efficacy of immune checkpoint inhibitors in advanced cancer patients with autoimmune disease: A meta-analysis

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