The correlation between proteoglycan 2 and neuropsychiatric systemic lupus erythematosus

Qiao, Xiaoyue; Lü, Li; Zhou, Kangxing; Tan, Liping; Li, Xuan; Ni, Jiali; Hou, Yayi; Liang, Jun; Dou, Huan

doi:10.1016/j.clim.2022.109042

Cited by 8 publications

(3 citation statements)

References 81 publications

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“…For an unbiased comparison, we performed RNA sequencing in cells overexpressing UNC93B1 V117L or T314A. From the most significantly upregulated genes, at least six are known biomarkers for disease activity in lupus (DEFB1 15 , PRLR 16 , S100A8/9 17 , FCER2 18 , PRG2 19 ) ( Supp Fig. 3a and 3d ).…”

Section: Unc93b1 Variants Drive Inflammation and Immune Dysfunction V...mentioning

confidence: 99%

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Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus

Al-Azab,

Idiiatullina,

Lin

et al. 2023

Preprint

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Rare genetic variants in TLR7 are known to cause lupus in humans and mice. UNC93B1 is a transmembrane protein that regulates TLR7 localisation into endosomes, however it has only been genetically linked to lupus in mice and dogs. We now identify a novel variant in UNC93B1 (T314A) located proximally to the TLR7 transmembrane domain, in a patient with childhood-onset systemic lupus erythematosus (SLE). Further examination in a cohort of East Asian patients revealed seven who encode UNC93B1 (V117L), which is a rare but highly significant risk factor for this disease, when compared to the corresponding general population. The variant is associated with increased expression of type I IFNs and NF-kB cytokines in patients plasma and PBMC. This was confirmed using cell line models, with exaggerated responses to stimulation of TLR7/8, but not TLR3 or TLR9, and the process can be inhibited by targeting the TLR signaling molecules IRAK1/4. For UNC93B1 (V117L) we then created the orthologous mutation in mice (V138L), which results in a spontaneous lupus-like disease in heterozygotes, that is more severe in homozygotes and again hyperresponsive to TLR7 stimulation. Together, this work formally identifies genetic variants in UNC93B1 that can predispose to childhood-onset SLE.

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Section: Unc93b1 Variants Drive Inflammation and Immune Dysfunction V...mentioning

confidence: 99%

“…From the most significantly upregulated genes, at least six are known biomarkers for disease activity in lupus (DEFB1 15 , PRLR 16 , S100A8/9 17 , FCER2 18 , PRG2 19 ) (Supp Fig. 3a and 3d).…”

Section: Unc93b1 Variants Drive Inflammation and Immune Dysfunction V...mentioning

confidence: 99%

Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus

Al-Azab,

Idiiatullina,

Lin

et al. 2023

Preprint

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“…Among these biomarkers, eosinophil cationic protein (ECP), traditionally recognized for its involvement in eosinophil-mediated immune responses, has gained attention as a potential player in the neuroinflammatory pathways implicated in schizophrenia. [5] ECP, a cytotoxic protein predominantly released by eosinophils upon activation, exhibits antimicrobial properties and regulatory effects on immune cells. Beyond its classical role in host defense against parasites and allergic responses, recent studies have begun to explore its broader immunomodulatory functions, prompting investigations into its potential involvement in neuroinflammatory processes relevant to schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Exploring the role of eosinophil cationic protein (ECP) in schizophrenia: Insights and implications

Obeagu

2024

Medicine

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Schizophrenia, a multifaceted neuropsychiatric disorder characterized by disruptions in perception, cognition, and behavior, has been associated with neuroinflammatory processes. Emerging research has increasingly recognized the potential involvement of immune-related factors in the pathogenesis of schizophrenia, prompting investigations into biomarkers associated with inflammatory cascades. Among these biomarkers, Eosinophil Cationic Protein (ECP), traditionally known for its role in eosinophil-mediated immune responses, has garnered attention for its putative association with neuroinflammation in schizophrenia. This paper critically examines the current understanding of the role of ECP in schizophrenia. ECP, a cytotoxic protein released by eosinophils, has diverse immunomodulatory effects and has been identified in altered concentrations in individuals with schizophrenia. Studies have reported elevated levels of ECP in peripheral fluids of schizophrenia patients, suggesting a possible link between ECP dysregulation and the inflammatory milieu characteristic of the disorder. Moreover, the potential implications of ECP in neuroinflammatory processes relevant to schizophrenia pathophysiology are discussed. ECP’s role in modulating immune responses and its potential impact on neuronal function, synaptic plasticity, and neurotoxicity within the central nervous system (CNS) are considered, highlighting the potential contribution of ECP to the neuroinflammatory mechanisms underlying schizophrenia. In conclusion, while the precise role of ECP in schizophrenia pathogenesis warrants further elucidation, exploring its association with neuroinflammation holds promise in unraveling new biomarkers and therapeutic avenues for managing this complex psychiatric disorder.

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Small molecule compound K-7174 attenuates neuropsychiatric manifestations in lupus-prone mice

Fan

et al. 2023

Brain Research

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The correlation between proteoglycan 2 and neuropsychiatric systemic lupus erythematosus

Cited by 8 publications

References 81 publications

Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus

Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus

Exploring the role of eosinophil cationic protein (ECP) in schizophrenia: Insights and implications

Small molecule compound K-7174 attenuates neuropsychiatric manifestations in lupus-prone mice

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